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| Publications of Henry Yin :chronological alphabetical combined listing:
%% Journal Articles
@article{fds374571,
Author = {Friedman, AD and Yin, HH},
Title = {Selective Activation of Subthalamic Nucleus Output
Quantitatively Scales Movements.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {43},
Number = {47},
Pages = {7967-7981},
Year = {2023},
Month = {November},
url = {http://dx.doi.org/10.1523/jneurosci.0734-23.2023},
Abstract = {The subthalamic nucleus (STN) is a common target for deep
brain stimulation (DBS) treatments of Parkinsonian motor
symptoms. According to the dominant model, the STN output
can suppress movement by enhancing inhibitory basal ganglia
(BG) output via the indirect pathway, and disrupting STN
output using DBS can restore movement in Parkinson's
patients. But the mechanisms underlying STN DBS remain
poorly understood, as previous studies usually relied on
electrical stimulation, which cannot selectively target STN
output neurons. Here, we selectively stimulated STN
projection neurons using optogenetics and quantified
behavior in male and female mice using 3D motion capture.
STN stimulation resulted in movements with short latencies
(10-15 ms). A single pulse of light was sufficient to
generate movement, and there was a highly linear
relationship between stimulation frequency and kinematic
measures. Unilateral stimulation caused movement in the
ipsiversive direction (toward the side of stimulation) and
quantitatively determined head yaw and head roll, while
stimulation of either STN raises the head (pitch). Bilateral
stimulation does not cause turning but raised the head twice
as high as unilateral stimulation of either STN. Optogenetic
stimulation increased the firing rate of STN neurons in a
frequency-dependent manner, and the increased firing is
responsible for stimulation-induced movements. Finally,
stimulation of the STN's projection to the brainstem
mesencephalic locomotor region was sufficient to reproduce
the behavioral effects of STN stimulation. These results
question the common assumption that the STN suppresses
movement, and instead suggest that STN output can precisely
specify action parameters via direct projections to the
brainstem.<b>SIGNIFICANCE STATEMENT</b> Our results question
the common assumption that the subthalamic nucleus (STN)
suppresses movement, and instead suggest that STN output can
precisely specify action parameters via direct projections
to the brainstem.},
Doi = {10.1523/jneurosci.0734-23.2023},
Key = {fds374571}
}
@article{fds372780,
Author = {Ulloa Severino and FP and Lawal, OO and Sakers, K and Wang, S and Kim, N and Friedman, AD and Johnson, SA and Sriworarat, C and Hughes, RH and Soderling, SH and Kim, IH and Yin, HH and Eroglu,
C},
Title = {Training-induced circuit-specific excitatory synaptogenesis
in mice is required for effort control.},
Journal = {Nat Commun},
Volume = {14},
Number = {1},
Pages = {5522},
Year = {2023},
Month = {September},
url = {http://dx.doi.org/10.1038/s41467-023-41078-z},
Abstract = {Synaptogenesis is essential for circuit development;
however, it is unknown whether it is critical for the
establishment and performance of goal-directed voluntary
behaviors. Here, we show that operant conditioning via
lever-press for food reward training in mice induces
excitatory synapse formation onto a subset of anterior
cingulate cortex neurons projecting to the dorsomedial
striatum (ACC→DMS). Training-induced synaptogenesis is
controlled by the Gabapentin/Thrombospondin receptor
α2δ-1, which is an essential neuronal protein for proper
intracortical excitatory synaptogenesis. Using germline and
conditional knockout mice, we found that deletion of α2δ-1
in the adult ACC→DMS circuit diminishes training-induced
excitatory synaptogenesis. Surprisingly, this manipulation
does not impact learning but results in a significant
increase in effort exertion without affecting sensitivity to
reward value or changing contingencies. Bidirectional
optogenetic manipulation of ACC→DMS neurons rescues or
phenocopies the behaviors of the α2δ-1 cKO mice,
highlighting the importance of synaptogenesis within this
cortico-striatal circuit in regulating effort
exertion.},
Doi = {10.1038/s41467-023-41078-z},
Key = {fds372780}
}
@article{fds371505,
Author = {Fallon, IP and Hughes, RN and Severino, FPU and Kim, N and Lawry, CM and Watson, GDR and Roshchina, M and Yin, HH},
Title = {The role of the parafascicular thalamic nucleus in action
initiation and steering.},
Journal = {Current biology : CB},
Volume = {33},
Number = {14},
Pages = {2941-2951.e4},
Year = {2023},
Month = {July},
url = {http://dx.doi.org/10.1016/j.cub.2023.06.025},
Abstract = {The parafascicular (Pf) nucleus of the thalamus has been
implicated in arousal and attention, but its contributions
to behavior remain poorly characterized. Here, using
in vivo and in vitro electrophysiology, optogenetics, and
3D motion capture, we studied the role of the Pf nucleus in
behavior using a continuous reward-tracking task in freely
moving mice. We found that many Pf neurons precisely
represent vector components of velocity, with a strong
preference for ipsiversive movements. Their activity usually
leads velocity, suggesting that Pf output is critical for
self-initiated orienting behavior. To test this hypothesis,
we expressed excitatory or inhibitory opsins in VGlut2+ Pf
neurons to manipulate neural activity bidirectionally. We
found that selective optogenetic stimulation of these
neurons consistently produced ipsiversive head turning,
whereas inhibition stopped turning and produced downward
movements. Taken together, our results suggest that the Pf
nucleus can send continuous top-down commands that specify
detailed action parameters (e.g., direction and speed of the
head), thus providing guidance for orienting and steering
during behavior.},
Doi = {10.1016/j.cub.2023.06.025},
Key = {fds371505}
}
@article{fds371654,
Author = {Naffaa, MM and Khan, RR and Kuo, CT and Yin, HH},
Title = {Cortical regulation of neurogenesis and cell proliferation
in the ventral subventricular zone.},
Journal = {Cell reports},
Volume = {42},
Number = {7},
Pages = {112783},
Year = {2023},
Month = {July},
url = {http://dx.doi.org/10.1016/j.celrep.2023.112783},
Abstract = {Neurogenesis and differentiation of neural stem cells (NSCs)
are controlled by cell-intrinsic molecular pathways that
interact with extrinsic signaling cues. In this study, we
identify a circuit that regulates neurogenesis and cell
proliferation in the lateral ventricle-subventricular zone
(LV-SVZ). Our results demonstrate that direct glutamatergic
projections from the anterior cingulate cortex (ACC), as
well as inhibitory projections from calretinin<sup>+</sup>
local interneurons, modulate the activity of cholinergic
neurons in the subependymal zone (subep-ChAT<sup>+</sup>).
Furthermore, in vivo optogenetic stimulation and inhibition
of the ACC-subep-ChAT<sup>+</sup> circuit are sufficient to
control neurogenesis in the ventral SVZ. Both
subep-ChAT<sup>+</sup> and local calretinin<sup>+</sup>
neurons play critical roles in regulating ventral SVZ
neurogenesis and LV-SVZ cell proliferation.},
Doi = {10.1016/j.celrep.2023.112783},
Key = {fds371654}
}
@article{fds365542,
Author = {Zhang, J and Hughes, RN and Kim, N and Fallon, IP and Bakhurin, K and Kim,
J and Severino, FPU and Yin, HH},
Title = {A one-photon endoscope for simultaneous patterned
optogenetic stimulation and calcium imaging in freely
behaving mice.},
Journal = {Nature biomedical engineering},
Volume = {7},
Number = {4},
Pages = {499-510},
Year = {2023},
Month = {April},
url = {http://dx.doi.org/10.1038/s41551-022-00920-3},
Abstract = {Optogenetics and calcium imaging can be combined to
simultaneously stimulate and record neural activity in vivo.
However, this usually requires two-photon microscopes, which
are not portable nor affordable. Here we report the design
and implementation of a miniaturized one-photon endoscope
for performing simultaneous optogenetic stimulation and
calcium imaging. By integrating digital micromirrors, the
endoscope makes it possible to activate any neuron of choice
within the field of view, and to apply arbitrary
spatiotemporal patterns of photostimulation while imaging
calcium activity. We used the endoscope to image striatal
neurons from either the direct pathway or the indirect
pathway in freely moving mice while activating any chosen
neuron in the field of view. The endoscope also allows for
the selection of neurons based on their relationship with
specific animal behaviour, and to recreate the behaviour by
mimicking the natural neural activity with photostimulation.
The miniaturized endoscope may facilitate the study of how
neural activity gives rise to behaviour in freely moving
animals.},
Doi = {10.1038/s41551-022-00920-3},
Key = {fds365542}
}
@article{fds370886,
Author = {Petter, EA and Fallon, IP and Hughes, RN and Watson, GDR and Meck, WH and Ulloa Severino and FP and Yin, HH},
Title = {Elucidating a locus coeruleus-dentate gyrus dopamine pathway
for operant reinforcement.},
Journal = {eLife},
Volume = {12},
Pages = {e83600},
Year = {2023},
Month = {April},
url = {http://dx.doi.org/10.7554/elife.83600},
Abstract = {Animals can learn to repeat behaviors to earn desired
rewards, a process commonly known as reinforcement learning.
While previous work has implicated the ascending
dopaminergic projections to the basal ganglia in
reinforcement learning, little is known about the role of
the hippocampus. Here, we report that a specific population
of hippocampal neurons and their dopaminergic innervation
contribute to operant self-stimulation. These neurons are
located in the dentate gyrus, receive dopaminergic
projections from the locus coeruleus, and express D1
dopamine receptors. Activation of D1 + dentate neurons is
sufficient for self-stimulation: mice will press a lever to
earn optogenetic activation of these neurons. A similar
effect is also observed with selective activation of the
locus coeruleus projections to the dentate gyrus, and
blocked by D1 receptor antagonism. Calcium imaging of D1 +
dentate neurons revealed significant activity at the time of
action selection, but not during passive reward delivery.
These results reveal the role of dopaminergic innervation of
the dentate gyrus in supporting operant reinforcement.},
Doi = {10.7554/elife.83600},
Key = {fds370886}
}
@article{fds364281,
Author = {Yu, C and Jiang, TT and Shoemaker, CT and Fan, D and Rossi, MA and Yin,
HH},
Title = {Striatal mechanisms of turning behaviour following
unilateral dopamine depletion in mice.},
Journal = {The European journal of neuroscience},
Volume = {56},
Number = {5},
Pages = {4529-4545},
Year = {2022},
Month = {September},
url = {http://dx.doi.org/10.1111/ejn.15764},
Abstract = {Unilateral dopamine (DA) depletion produces ipsiversive
turning behaviour, and the injection of DA receptor agonists
can produce contraversive turning, but the underlying
mechanisms remain unclear. We conducted in vivo recording
and pharmacological and optogenetic manipulations to study
the role of DA and striatal output in turning behaviour. We
used a video-based tracking programme while recording single
unit activity in both putative medium spiny projection
neurons (MSNs) and fast-spiking interneurons (FSIs) in the
dorsal striatum bilaterally. Our results suggest that
unilateral DA depletion reduced striatal output from the
depleted side, resulting in asymmetric striatal output.
Depletion systematically altered activity in both MSNs and
FSIs, especially in neurons that increased firing during
turning movements. Like D1 agonist SKF 38393, optogenetic
stimulation in the depleted striatum increased striatal
output and reversed biassed turning. These results suggest
that relative striatal outputs from the two cerebral
hemispheres determine the direction of turning: Mice turn
away from the side of higher striatal output and towards the
side of the lower striatal output.},
Doi = {10.1111/ejn.15764},
Key = {fds364281}
}
@article{fds363848,
Author = {Kim, S and Kim, Y-E and Song, I and Ujihara, Y and Kim, N and Jiang, Y-H and Yin, HH and Lee, T-H and Kim, IH},
Title = {Neural circuit pathology driven by Shank3 mutation disrupts
social behaviors.},
Journal = {Cell reports},
Volume = {39},
Number = {10},
Pages = {110906},
Year = {2022},
Month = {June},
url = {http://dx.doi.org/10.1016/j.celrep.2022.110906},
Abstract = {Dysfunctional sociability is a core symptom in autism
spectrum disorder (ASD) that may arise from neural-network
dysconnectivity between multiple brain regions. However,
pathogenic neural-network mechanisms underlying social
dysfunction are largely unknown. Here, we demonstrate that
circuit-selective mutation (ctMUT) of ASD-risk Shank3 gene
within a unidirectional projection from the prefrontal
cortex to the basolateral amygdala alters spine morphology
and excitatory-inhibitory balance of the circuit. Shank3
ctMUT mice show reduced sociability as well as elevated
neural activity and its amplitude variability, which is
consistent with the neuroimaging results from human ASD
patients. Moreover, the circuit hyper-activity disrupts the
temporal correlation of socially tuned neurons to the events
of social interactions. Finally, optogenetic circuit
activation in wild-type mice partially recapitulates the
reduced sociability of Shank3 ctMUT mice, while circuit
inhibition in Shank3 ctMUT mice partially rescues social
behavior. Collectively, these results highlight a
circuit-level pathogenic mechanism of Shank3 mutation that
drives social dysfunction.},
Doi = {10.1016/j.celrep.2022.110906},
Key = {fds363848}
}
@article{fds362516,
Author = {Bakhurin, KI and Yin, HH},
Title = {Closing the loop on models of interval timing.},
Journal = {Nature neuroscience},
Volume = {25},
Number = {3},
Pages = {270-271},
Year = {2022},
Month = {March},
url = {http://dx.doi.org/10.1038/s41593-022-01015-7},
Doi = {10.1038/s41593-022-01015-7},
Key = {fds362516}
}
@article{fds361814,
Author = {Barter, JW and Yin, HH},
Title = {Achieving natural behavior in a robot using neurally
inspired hierarchical perceptual control},
Journal = {iScience},
Volume = {24},
Number = {9},
Year = {2021},
Month = {September},
url = {http://dx.doi.org/10.1016/j.isci.2021.102948},
Abstract = {Terrestrial locomotion presents tremendous computational
challenges on account of the enormous degrees of freedom in
legged animals, and complex, unpredictable properties of
natural environments, including the body and its effectors,
yet the nervous system can achieve locomotion with ease.
Here we introduce a quadrupedal robot that is capable of
posture control and goal-directed locomotion across uneven
terrain. The control architecture is a hierarchical network
of simple negative feedback control systems inspired by the
organization of the vertebrate nervous system. This robot is
capable of robust posture control and locomotion in novel
environments with unpredictable disturbances. Unlike current
robots, our robot does not use internal inverse and forward
models, nor does it require any training in order to perform
successfully in novel environments.},
Doi = {10.1016/j.isci.2021.102948},
Key = {fds361814}
}
@article{fds356460,
Author = {Hughes, RN and Watson, GDR and Petter, EA and Kim, N and Bakhurin, KI and Yin, HH},
Title = {Precise coordination of three-dimensional rotational
kinematics by ventral tegmental area GABAergic
neurons.},
Journal = {Current biology : CB},
Volume = {31},
Number = {9},
Pages = {2037},
Year = {2021},
Month = {May},
url = {http://dx.doi.org/10.1016/j.cub.2021.04.008},
Doi = {10.1016/j.cub.2021.04.008},
Key = {fds356460}
}
@article{fds354955,
Author = {Li, HE and Rossi, MA and Watson, GDR and Moore, HG and Cai, MT and Kim, N and Vokt, KA and Lu, D and Bartholomew, RA and Hughes, RN and Yin,
HH},
Title = {Hypothalamic-Extended Amygdala Circuit Regulates Temporal
Discounting.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {41},
Number = {9},
Pages = {1928-1940},
Year = {2021},
Month = {March},
url = {http://dx.doi.org/10.1523/jneurosci.1836-20.2020},
Abstract = {Choice behavior is characterized by temporal discounting,
i.e., preference for immediate rewards given a choice
between immediate and delayed rewards. Agouti-related
peptide (AgRP)-expressing neurons located in the arcuate
nucleus of the hypothalamus (ARC) regulate food intake and
energy homeostasis, yet whether AgRP neurons influence
choice behavior and temporal discounting is unknown. Here,
we demonstrate that motivational state potently modulates
temporal discounting. Hungry mice (both male and female)
strongly preferred immediate food rewards, yet sated mice
were largely indifferent to reward delay. More importantly,
selective optogenetic activation of AgRP-expressing neurons
or their axon terminals within the posterior bed nucleus of
stria terminalis (BNST) produced temporal discounting in
sated mice. Furthermore, activation of neuropeptide Y (NPY)
type 1 receptors (Y1Rs) within the BNST is sufficient to
produce temporal discounting. These results demonstrate a
profound influence of hypothalamic signaling on temporal
discounting for food rewards and reveal a novel circuit that
determine choice behavior.<b>SIGNIFICANCE STATEMENT</b>
Temporal discounting is a universal phenomenon found in many
species, yet the underlying neurocircuit mechanisms are
still poorly understood. Our results revealed a novel neural
pathway from agouti-related peptide (AgRP) neurons in the
hypothalamus to the bed nucleus of stria terminalis (BNST)
that regulates temporal discounting in decision-making.},
Doi = {10.1523/jneurosci.1836-20.2020},
Key = {fds354955}
}
@article{fds355155,
Author = {Watson, GDR and Hughes, RN and Petter, EA and Fallon, IP and Kim, N and Severino, FPU and Yin, HH},
Title = {Thalamic projections to the subthalamic nucleus contribute
to movement initiation and rescue of parkinsonian
symptoms.},
Journal = {Science advances},
Volume = {7},
Number = {6},
Pages = {eabe9192},
Year = {2021},
Month = {February},
url = {http://dx.doi.org/10.1126/sciadv.abe9192},
Abstract = {The parafascicular nucleus (Pf) of the thalamus provides
major projections to the basal ganglia, a set of subcortical
nuclei involved in action initiation. Here, we show that Pf
projections to the subthalamic nucleus (STN), but not to the
striatum, are responsible for movement initiation. Because
the STN is a major target of deep brain stimulation
treatments for Parkinson's disease, we tested the effect of
selective stimulation of Pf-STN projections in a mouse model
of PD. Bilateral dopamine depletion with 6-OHDA created
complete akinesia in mice, but Pf-STN stimulation
immediately and markedly restored a variety of natural
behaviors. Our results therefore revealed a functionally
novel neural pathway for the initiation of movements that
can be recruited to rescue movement deficits after dopamine
depletion. They not only shed light on the clinical efficacy
of conventional STN DBS but also suggest more selective and
improved stimulation strategies for the treatment of
parkinsonian symptoms.},
Doi = {10.1126/sciadv.abe9192},
Key = {fds355155}
}
@article{fds357563,
Author = {Bakhurin, KI and Hughes, RN and Barter, JW and Zhang, J and Yin,
HH},
Title = {Protocol for Recording from Ventral Tegmental Area Dopamine
Neurons in Mice while Measuring Force during
Head-Fixation.},
Journal = {STAR protocols},
Volume = {1},
Number = {2},
Pages = {100091},
Year = {2020},
Month = {September},
url = {http://dx.doi.org/10.1016/j.xpro.2020.100091},
Abstract = {Many studies in systems neuroscience use head-fixation
preparations for <i>in vivo</i> experimentation. While
head-fixation confers several advantages, one major
limitation is the lack of behavioral measures that quantify
whole-body movements. Here, we detail a step-by-step
protocol for using a novel head-fixation device that
measures the forces exerted by head-fixed mice in multiple
dimensions. We further detail how this system can be used in
conjunction with <i>in vivo</i> electrophysiology and
optogenetics to study dopamine neurons in the ventral
tegmental area. For complete details on the use and
execution of this protocol, please refer to Hughes et al.
(2020a, 2020b).},
Doi = {10.1016/j.xpro.2020.100091},
Key = {fds357563}
}
@article{fds351481,
Author = {Lusk, N and Meck, WH and Yin, HH},
Title = {Mediodorsal Thalamus Contributes to the Timing of
Instrumental Actions.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {40},
Number = {33},
Pages = {6379-6388},
Year = {2020},
Month = {August},
url = {http://dx.doi.org/10.1523/jneurosci.0695-20.2020},
Abstract = {The perception of time is critical to adaptive behavior.
While prefrontal cortex and basal ganglia have been
implicated in interval timing in the seconds to minutes
range, little is known about the role of the mediodorsal
thalamus (MD), which is a key component of the limbic
cortico-basal ganglia-thalamocortical loop. In this study,
we tested the role of the MD in timing, using an operant
temporal production task in male mice. In this task, that
the expected timing of available rewards is indicated by
lever pressing. Inactivation of the MD with muscimol
produced rightward shifts in peak pressing on probe trials
as well as increases in peak spread, thus significantly
altering both temporal accuracy and precision. Optogenetic
inhibition of glutamatergic projection neurons in the MD
also resulted in similar changes in timing. The observed
effects were found to be independent of significant changes
in movement. Our findings suggest that the MD is a critical
component of the neural circuit for interval timing, without
playing a direct role in regulating ongoing
performance.<b>SIGNIFICANCE STATEMENT</b> The mediodorsal
nucleus (MD) of the thalamus is strongly connected with the
prefrontal cortex and basal ganglia, areas which have been
implicated in interval timing. Previous work has shown that
the MD contributes to working memory and learning of
action-outcome contingencies, but its role in behavioral
timing is poorly understood. Using an operant temporal
production task, we showed that inactivation of the MD
significantly impaired timing behavior.},
Doi = {10.1523/jneurosci.0695-20.2020},
Key = {fds351481}
}
@article{fds351197,
Author = {Kim, IH and Kim, N and Kim, S and Toda, K and Catavero, CM and Courtland,
JL and Yin, HH and Soderling, SH},
Title = {Dysregulation of the Synaptic Cytoskeleton in the PFC Drives
Neural Circuit Pathology, Leading to Social
Dysfunction.},
Journal = {Cell Rep},
Volume = {32},
Number = {4},
Pages = {107965},
Year = {2020},
Month = {July},
url = {http://dx.doi.org/10.1016/j.celrep.2020.107965},
Abstract = {Psychiatric disorders are highly heritable pathologies of
altered neural circuit functioning. How genetic mutations
lead to specific neural circuit abnormalities underlying
behavioral disruptions, however, remains unclear. Using
circuit-selective transgenic tools and a mouse model of
maladaptive social behavior (ArpC3 mutant), we identify a
neural circuit mechanism driving dysfunctional social
behavior. We demonstrate that circuit-selective knockout
(ctKO) of the ArpC3 gene within prefrontal cortical neurons
that project to the basolateral amygdala elevates the
excitability of the circuit neurons, leading to disruption
of socially evoked neural activity and resulting in abnormal
social behavior. Optogenetic activation of this circuit in
wild-type mice recapitulates the social dysfunction observed
in ArpC3 mutant mice. Finally, the maladaptive sociability
of ctKO mice is rescued by optogenetically silencing neurons
within this circuit. These results highlight a mechanism of
how a gene-to-neural circuit interaction drives altered
social behavior, a common phenotype of several psychiatric
disorders.},
Doi = {10.1016/j.celrep.2020.107965},
Key = {fds351197}
}
@article{fds349931,
Author = {Hughes, RN and Bakhurin, KI and Petter, EA and Watson, GDR and Kim, N and Friedman, AD and Yin, HH},
Title = {Ventral Tegmental Dopamine Neurons Control the Impulse
Vector during Motivated Behavior.},
Journal = {Current biology : CB},
Volume = {30},
Number = {14},
Pages = {2681-2694.e5},
Year = {2020},
Month = {July},
url = {http://dx.doi.org/10.1016/j.cub.2020.05.003},
Abstract = {The ventral tegmental area (VTA) is a major source of
dopamine, especially to the limbic brain regions. Despite
decades of research, the function of VTA dopamine neurons
remains controversial. Here, using a novel head-fixed
behavioral system with five orthogonal force sensors, we
show for the first time that the activity of dopamine
neurons precisely represents the impulse vector (force
exerted over time) generated by the animal. Distinct
populations of VTA dopamine neurons contribute to components
of the impulse vector in different directions. Optogenetic
excitation of these neurons shows a linear relationship
between signal injected and impulse generated. Optogenetic
inhibition paused force generation or produced force in the
backward direction. At the same time, these neurons also
regulate the initiation and execution of anticipatory
licking. Our results indicate that VTA dopamine controls the
magnitude, direction, and duration of force used to move
toward or away from any motivationally relevant
stimuli.},
Doi = {10.1016/j.cub.2020.05.003},
Key = {fds349931}
}
@article{fds349629,
Author = {Bakhurin, KI and Li, X and Friedman, AD and Lusk, NA and Watson, GD and Kim, N and Yin, HH},
Title = {Opponent regulation of action performance and timing by
striatonigral and striatopallidal pathways.},
Journal = {eLife},
Volume = {9},
Pages = {e54831},
Year = {2020},
Month = {April},
url = {http://dx.doi.org/10.7554/elife.54831},
Abstract = {The basal ganglia have been implicated in action selection
and timing, but the relative contributions of the
striatonigral (direct) and striatopallidal (indirect)
pathways to these functions remain unclear. We investigated
the effects of optogenetic stimulation of D1+ (direct) and
A2A+ (indirect) neurons in the ventrolateral striatum in
head-fixed mice on a fixed time reinforcement schedule.
Direct pathway stimulation initiates licking, whereas
indirect pathway stimulation suppresses licking and results
in rebound licking after stimulation. Moreover, direct and
indirect pathways also play distinct roles in timing. Direct
pathway stimulation produced a resetting of the internal
timing process, whereas indirect pathway stimulation
transiently paused timing, and proportionally delayed the
next bout of licking. Our results provide evidence for the
continuous and opposing contributions of the direct and
indirect pathways in the production and timing of
reward-guided behavior.},
Doi = {10.7554/elife.54831},
Key = {fds349629}
}
@article{fds366579,
Author = {Burrus, CJ and McKinstry, SU and Kim, N and Ozlu, MI and Santoki, AV and Fang, FY and Ma, A and Karadeniz, YB and Worthington, AK and Dragatsis,
I and Zeitlin, S and Yin, HH and Eroglu, C},
Title = {Striatal Projection Neurons Require Huntingtin for Synaptic
Connectivity and Survival.},
Journal = {Cell Rep},
Volume = {30},
Number = {3},
Pages = {642-657.e6},
Year = {2020},
Month = {January},
url = {http://dx.doi.org/10.1016/j.celrep.2019.12.069},
Abstract = {Huntington's disease (HD) is caused by an autosomal dominant
polyglutamine expansion mutation of Huntingtin (HTT). HD
patients suffer from progressive motor, cognitive, and
psychiatric impairments, along with significant degeneration
of the striatal projection neurons (SPNs) of the striatum.
HD is widely accepted to be caused by a toxic
gain-of-function of mutant HTT. However, whether loss of HTT
function, because of dominant-negative effects of the mutant
protein, plays a role in HD and whether HTT is required for
SPN health and function are not known. Here, we delete Htt
from specific subpopulations of SPNs using the Cre-Lox
system and find that SPNs require HTT for motor regulation,
synaptic development, cell health, and survival during
aging. Our results suggest that loss of HTT function in SPNs
could play a critical role in HD pathogenesis.},
Doi = {10.1016/j.celrep.2019.12.069},
Key = {fds366579}
}
@article{fds349122,
Author = {Hughes, RN and Bakhurin, KI and Barter, JW and Zhang, J and Yin,
HH},
Title = {A Head-Fixation System for Continuous Monitoring of Force
Generated During Behavior.},
Journal = {Frontiers in integrative neuroscience},
Volume = {14},
Pages = {11},
Year = {2020},
Month = {January},
url = {http://dx.doi.org/10.3389/fnint.2020.00011},
Abstract = {Many studies in neuroscience use head-fixed behavioral
preparations, which confer a number of advantages, including
the ability to limit the behavioral repertoire and use
techniques for large-scale monitoring of neural activity.
But traditional studies using this approach use extremely
limited behavioral measures, in part because it is difficult
to detect the subtle movements and postural adjustments that
animals naturally exhibit during head fixation. Here we
report a new head-fixed setup with analog load cells capable
of precisely monitoring the continuous forces exerted by
mice. The load cells reveal the dynamic nature of movements
generated not only around the time of task-relevant events,
such as presentation of stimuli and rewards, but also during
periods in between these events, when there is no apparent
overt behavior. It generates a new and rich set of
behavioral measures that have been neglected in previous
experiments. We detail the construction of the system, which
can be 3D-printed and assembled at low cost, show behavioral
results collected from head-fixed mice, and demonstrate that
neural activity can be highly correlated with the subtle,
whole-body movements continuously produced during head
restraint.},
Doi = {10.3389/fnint.2020.00011},
Key = {fds349122}
}
@article{fds346602,
Author = {Hughes, RN and Watson, GDR and Petter, EA and Kim, N and Bakhurin, KI and Yin, HH},
Title = {Precise Coordination of Three-Dimensional Rotational
Kinematics by Ventral Tegmental Area GABAergic
Neurons.},
Journal = {Current biology : CB},
Volume = {29},
Number = {19},
Pages = {3244-3255.e4},
Year = {2019},
Month = {October},
url = {http://dx.doi.org/10.1016/j.cub.2019.08.022},
Abstract = {The ventral tegmental area (VTA) is a midbrain region
implicated in a variety of motivated behaviors. However, the
function of VTA GABAergic (Vgat+) neurons remains poorly
understood. Here, using three-dimensional motion capture,
in vivo electrophysiology, calcium imaging, and
optogenetics, we demonstrate a novel function of
VTA<sup>Vgat+</sup> neurons. We found three distinct
populations of neurons, each representing head angle about a
principal axis of rotation: yaw, roll, and pitch. For each
axis, opponent cell groups were found that increase firing
when the head moves in one direction and decrease firing in
the opposite direction. Selective excitation and inhibition
of VTA<sup>Vgat+</sup> neurons generate opposite rotational
movements. Thus, VTA<sup>Vgat+</sup> neurons serve a
critical role in the control of rotational kinematics while
pursuing a moving target. This general-purpose steering
function can guide animals toward desired spatial targets in
any motivated behavior.},
Doi = {10.1016/j.cub.2019.08.022},
Key = {fds346602}
}
@article{fds345031,
Author = {Yang, R and Walder-Christensen, KK and Kim, N and Wu, D and Lorenzo, DN and Badea, A and Jiang, Y-H and Yin, HH and Wetsel, WC and Bennett,
V},
Title = {ANK2 autism mutation targeting giant ankyrin-B promotes axon
branching and ectopic connectivity.},
Journal = {Proc Natl Acad Sci U S A},
Volume = {116},
Number = {30},
Pages = {15262-15271},
Year = {2019},
Month = {July},
url = {http://dx.doi.org/10.1073/pnas.1904348116},
Abstract = {Giant ankyrin-B (ankB) is a neurospecific alternatively
spliced variant of ANK2, a high-confidence autism spectrum
disorder (ASD) gene. We report that a mouse model for human
ASD mutation of giant ankB exhibits increased axonal
branching in cultured neurons with ectopic CNS axon
connectivity, as well as with a transient increase in
excitatory synapses during postnatal development. We
elucidate a mechanism normally limiting axon branching,
whereby giant ankB localizes to periodic axonal plasma
membrane domains through L1 cell-adhesion molecule protein,
where it couples microtubules to the plasma membrane and
prevents microtubule entry into nascent axon branches. Giant
ankB mutation or deficiency results in a dominantly
inherited impairment in selected communicative and social
behaviors combined with superior executive function. Thus,
gain of axon branching due to giant ankB-deficiency/mutation
is a candidate cellular mechanism to explain aberrant
structural connectivity and penetrant behavioral
consequences in mice as well as humans bearing ASD-related
ANK2 mutations.},
Doi = {10.1073/pnas.1904348116},
Key = {fds345031}
}
@article{fds343720,
Author = {Kim, N and Li, HE and Hughes, RN and Watson, GDR and Gallegos, D and West,
AE and Kim, IH and Yin, HH},
Title = {A striatal interneuron circuit for continuous target
pursuit.},
Journal = {Nat Commun},
Volume = {10},
Number = {1},
Pages = {2715},
Year = {2019},
Month = {June},
url = {http://dx.doi.org/10.1038/s41467-019-10716-w},
Abstract = {Most adaptive behaviors require precise tracking of targets
in space. In pursuit behavior with a moving target, mice use
distance to target to guide their own movement continuously.
Here, we show that in the sensorimotor striatum,
parvalbumin-positive fast-spiking interneurons (FSIs) can
represent the distance between self and target during
pursuit behavior, while striatal projection neurons (SPNs),
which receive FSI projections, can represent self-velocity.
FSIs are shown to regulate velocity-related SPN activity
during pursuit, so that movement velocity is continuously
modulated by distance to target. Moreover, bidirectional
manipulation of FSI activity can selectively disrupt
performance by increasing or decreasing the self-target
distance. Our results reveal a key role of the FSI-SPN
interneuron circuit in pursuit behavior and elucidate how
this circuit implements distance to velocity transformation
required for the critical underlying computation.},
Doi = {10.1038/s41467-019-10716-w},
Key = {fds343720}
}
@article{fds341738,
Author = {Risher, WC and Kim, N and Koh, S and Choi, J-E and Mitev, P and Spence, EF and Pilaz, L-J and Wang, D and Feng, G and Silver, DL and Soderling, SH and Yin, HH and Eroglu, C},
Title = {Thrombospondin receptor α2δ-1 promotes synaptogenesis and
spinogenesis via postsynaptic Rac1.},
Journal = {J Cell Biol},
Volume = {217},
Number = {10},
Pages = {3747-3765},
Year = {2018},
Month = {October},
url = {http://dx.doi.org/10.1083/jcb.201802057},
Abstract = {Astrocytes control excitatory synaptogenesis by secreting
thrombospondins (TSPs), which function via their neuronal
receptor, the calcium channel subunit α2δ-1. α2δ-1 is a
drug target for epilepsy and neuropathic pain; thus the
TSP-α2δ-1 interaction is implicated in both synaptic
development and disease pathogenesis. However, the mechanism
by which this interaction promotes synaptogenesis and the
requirement for α2δ-1 for connectivity of the developing
mammalian brain are unknown. In this study, we show that
global or cell-specific loss of α2δ-1 yields profound
deficits in excitatory synapse numbers, ultrastructure, and
activity and severely stunts spinogenesis in the mouse
cortex. Postsynaptic but not presynaptic α2δ-1 is required
and sufficient for TSP-induced synaptogenesis in vitro and
spine formation in vivo, but an α2δ-1 mutant linked to
autism cannot rescue these synaptogenesis defects. Finally,
we reveal that TSP-α2δ-1 interactions control
synaptogenesis postsynaptically via Rac1, suggesting
potential molecular mechanisms that underlie both synaptic
development and pathology.},
Doi = {10.1083/jcb.201802057},
Key = {fds341738}
}
@article{fds341599,
Author = {Tan, S and Xiao, Y and Yin, HH and Chen, AI and Soong, TW and Je,
HS},
Title = {Postnatal TrkB ablation in corticolimbic interneurons
induces social dominance in male mice.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {115},
Number = {42},
Pages = {E9909-E9915},
Year = {2018},
Month = {October},
url = {http://dx.doi.org/10.1073/pnas.1812083115},
Abstract = {The tight balance between synaptic excitation and inhibition
(E/I) within neocortical circuits in the mammalian brain is
important for complex behavior. Many loss-of-function
studies have demonstrated that brain-derived neurotrophic
factor (BDNF) and its cognate receptor tropomyosin receptor
kinase B (TrkB) are essential for the development of
inhibitory GABAergic neurons. However, behavioral
consequences of impaired BDNF/TrkB signaling in GABAergic
neurons remain unclear, largely due to confounding motor
function deficits observed in previous animal models. In
this study, we generated conditional knockout mice (TrkB
cKO) in which TrkB was ablated from a majority of
corticolimbic GABAergic interneurons postnatally. These mice
showed intact motor coordination and movement, but exhibited
enhanced dominance over other mice in a group-housed
setting. In addition, immature fast-spiking GABAergic
neurons of TrkB cKO mice resulted in an E/I imbalance in
layer 5 microcircuits within the medial prefrontal cortex
(mPFC), a key region regulating social dominance. Restoring
the E/I imbalance via optogenetic modulation in the mPFC of
TrkB cKO mice normalized their social dominance behavior.
Taken together, our results provide strong evidence for a
role of BDNF/TrkB signaling in inhibitory synaptic
modulation and social dominance behavior in
mice.},
Doi = {10.1073/pnas.1812083115},
Key = {fds341599}
}
@article{fds336562,
Author = {Rodriguez, E and Sakurai, K and Xu, J and Chen, Y and Toda, K and Zhao, S and Han, B-X and Ryu, D and Yin, H and Liedtke, W and Wang,
F},
Title = {Publisher Correction: A craniofacial-specific monosynaptic
circuit enables heightened affective pain.},
Journal = {Nat Neurosci},
Volume = {21},
Number = {6},
Pages = {896},
Year = {2018},
Month = {June},
url = {http://dx.doi.org/10.1038/s41593-018-0103-7},
Abstract = {In the version of this article initially published, ORCID
links were missing for authors Erica Rodriguez, Koji Toda
and Fan Wang. The error has been corrected in the HTML and
PDF versions of the article.},
Doi = {10.1038/s41593-018-0103-7},
Key = {fds336562}
}
@article{fds336561,
Author = {Bey, AL and Wang, X and Yan, H and Kim, N and Passman, RL and Yang, Y and Cao,
X and Towers, AJ and Hulbert, SW and Duffney, LJ and Gaidis, E and Rodriguiz, RM and Wetsel, WC and Yin, HH and Jiang,
Y-H},
Title = {Brain region-specific disruption of Shank3 in mice reveals a
dissociation for cortical and striatal circuits in
autism-related behaviors.},
Journal = {Transl Psychiatry},
Volume = {8},
Number = {1},
Pages = {94},
Year = {2018},
Month = {April},
url = {http://dx.doi.org/10.1038/s41398-018-0142-6},
Abstract = {We previously reported a new line of Shank3 mutant mice
which led to a complete loss of Shank3 by deleting exons
4-22 (Δe4-22) globally. Δe4-22 mice display robust
ASD-like behaviors including impaired social interaction and
communication, increased stereotypical behavior and
excessive grooming, and a profound deficit in instrumental
learning. However, the anatomical and neural circuitry
underlying these behaviors are unknown. We generated mice
with Shank3 selectively deleted in forebrain, striatum, and
striatal D1 and D2 cells. These mice were used to
interrogate the circuit/brain-region and cell-type specific
role of Shank3 in the expression of autism-related
behaviors. Whole-cell patch recording and biochemical
analyses were used to study the synaptic function and
molecular changes in specific brain regions. We found
perseverative exploratory behaviors in mice with deletion of
Shank3 in striatal inhibitory neurons. Conversely,
self-grooming induced lesions were observed in mice with
deletion of Shank3 in excitatory neurons of forebrain.
However, social, communicative, and instrumental learning
behaviors were largely unaffected in these mice, unlike what
is seen in global Δe4-22 mice. We discovered unique
patterns of change for the biochemical and
electrophysiological findings in respective brain regions
that reflect the complex nature of transcriptional
regulation of Shank3. Reductions in Homer1b/c and membrane
hyper-excitability were observed in striatal loss of Shank3.
By comparison, Shank3 deletion in hippocampal neurons
resulted in increased NMDAR-currents and GluN2B-containing
NMDARs. These results together suggest that Shank3 may
differentially regulate neural circuits that control
behavior. Our study supports a dissociation of Shank3
functions in cortical and striatal neurons in ASD-related
behaviors, and it illustrates the complexity of neural
circuit mechanisms underlying these behaviors.},
Doi = {10.1038/s41398-018-0142-6},
Key = {fds336561}
}
@article{fds330361,
Author = {O'Hare, J and Calakos, N and Yin, HH},
Title = {Recent Insights into Corticostriatal Circuit Mechanisms
underlying Habits: Invited review for Current Opinions in
Behavioral Sciences.},
Journal = {Curr Opin Behav Sci},
Volume = {20},
Pages = {40-46},
Year = {2018},
Month = {April},
url = {http://dx.doi.org/10.1016/j.cobeha.2017.10.001},
Abstract = {Habits have been studied for decades, but it was not until
recent years that experiments began to elucidate the
underlying cellular and circuit mechanisms. The latest
experiments have been enabled by advances in cell-type
specific monitoring and manipulation of activity in large
neuronal populations. Here we will review recent efforts to
understand the neural substrates underlying habit formation,
focusing on rodent studies on corticostriatal
circuits.},
Doi = {10.1016/j.cobeha.2017.10.001},
Key = {fds330361}
}
@article{fds330362,
Author = {Rodriguez, E and Sakurai, K and Xu, J and Chen, Y and Toda, K and Zhao, S and Han, B-X and Ryu, D and Yin, H and Liedtke, W and Wang,
F},
Title = {A craniofacial-specific monosynaptic circuit enables
heightened affective pain.},
Journal = {Nat Neurosci},
Volume = {20},
Number = {12},
Pages = {1734-1743},
Year = {2017},
Month = {December},
url = {http://dx.doi.org/10.1038/s41593-017-0012-1},
Abstract = {Humans often rank craniofacial pain as more severe than body
pain. Evidence suggests that a stimulus of the same
intensity induces stronger pain in the face than in the
body. However, the underlying neural circuitry for the
differential processing of facial versus bodily pain remains
unknown. Interestingly, the lateral parabrachial nucleus
(PBL), a critical node in the affective pain circuit, is
activated more strongly by noxious stimulation of the face
than of the hindpaw. Using a novel activity-dependent
technology called CANE developed in our laboratory, we
identified and selectively labeled noxious-stimulus-activated
PBL neurons and performed comprehensive anatomical
input-output mapping. Surprisingly, we uncovered a hitherto
uncharacterized monosynaptic connection between cranial
sensory neurons and the PBL-nociceptive neurons. Optogenetic
activation of this monosynaptic craniofacial-to-PBL
projection induced robust escape and avoidance behaviors and
stress calls, whereas optogenetic silencing specifically
reduced facial nociception. The monosynaptic circuit
revealed here provides a neural substrate for heightened
craniofacial affective pain.},
Doi = {10.1038/s41593-017-0012-1},
Key = {fds330362}
}
@article{fds330363,
Author = {Toda, K and Lusk, NA and Watson, GDR and Kim, N and Lu, D and Li, HE and Meck,
WH and Yin, HH},
Title = {Nigrotectal Stimulation Stops Interval Timing in
Mice.},
Journal = {Current biology : CB},
Volume = {27},
Number = {24},
Pages = {3763-3770.e3},
Year = {2017},
Month = {December},
url = {http://dx.doi.org/10.1016/j.cub.2017.11.003},
Abstract = {Considerable evidence implicates the basal ganglia in
interval timing, yet the underlying mechanisms remain poorly
understood. Using a novel behavioral task, we demonstrate
that head-fixed mice can be trained to show the key features
of timing behavior within a few sessions. Single-trial
analysis of licking behavior reveals stepping dynamics with
variable onset times, which is responsible for the canonical
Gaussian distribution of timing behavior. Moreover, the
duration of licking bouts decreased as mice became sated,
showing a strong motivational modulation of licking bout
initiation and termination. Using optogenetics, we examined
the role of the basal ganglia output in interval timing. We
stimulated a pathway important for licking behavior, the
GABAergic output projections from the substantia nigra pars
reticulata to the deep layers of the superior colliculus. We
found that stimulation of this pathway not only cancelled
licking but also delayed the initiation of anticipatory
licking for the next interval in a frequency-dependent
manner. By combining quantitative behavioral analysis with
optogenetics in the head-fixed setup, we established a new
approach for studying the neural basis of interval
timing.},
Doi = {10.1016/j.cub.2017.11.003},
Key = {fds330363}
}
@article{fds363698,
Author = {Pappas, AL and Bey, AL and Wang, X and Rossi, M and Kim, YH and Yan, H and Porkka, F and Duffney, LJ and Phillips, SM and Cao, X and Ding, J-D and Rodriguiz, RM and Yin, HH and Weinberg, RJ and Ji, R-R and Wetsel, WC and Jiang, Y-H},
Title = {Deficiency of Shank2 causes mania-like behavior that
responds to mood stabilizers.},
Journal = {JCI Insight},
Volume = {2},
Number = {20},
Pages = {92052},
Year = {2017},
Month = {October},
url = {http://dx.doi.org/10.1172/jci.insight.92052},
Abstract = {Genetic defects in the synaptic scaffolding protein gene,
SHANK2, are linked to a variety of neuropsychiatric
disorders, including autism spectrum disorders,
schizophrenia, intellectual disability, and bipolar
disorder, but the molecular mechanisms underlying the
pleotropic effects of SHANK2 mutations are poorly
understood. We generated and characterized a line of Shank2
mutant mice by deleting exon 24 (Δe24). Shank2Δe24-/- mice
engage in significantly increased locomotor activity,
display abnormal reward-seeking behavior, are anhedonic,
have perturbations in circadian rhythms, and show deficits
in social and cognitive behaviors. While these phenotypes
recapitulate the pleotropic behaviors associated with human
SHANK2-related disorders, major behavioral features in these
mice are reminiscent of bipolar disorder. For instance,
their hyperactivity was augmented with amphetamine but was
normalized with the mood stabilizers lithium and valproate.
Shank2 deficiency limited to the forebrain recapitulated the
bipolar mania phenotype. The composition and functions of
NMDA and AMPA receptors were altered at Shank2-deficient
synapses, hinting toward the mechanism underlying these
behavioral abnormalities. Human genetic findings support
construct validity, and the behavioral features in Shank2
Δe24 mice support face and predictive validities of this
model for bipolar mania. Further genetic studies to
understand the contribution of SHANK2 deficiencies in
bipolar disorder are warranted.},
Doi = {10.1172/jci.insight.92052},
Key = {fds363698}
}
@article{fds330155,
Author = {O'Hare, JK and Li, H and Kim, N and Gaidis, E and Ade, K and Beck, J and Yin,
H and Calakos, N},
Title = {Striatal fast-spiking interneurons selectively modulate
circuit output and are required for habitual
behavior.},
Journal = {Elife},
Volume = {6},
Year = {2017},
Month = {September},
url = {http://dx.doi.org/10.7554/eLife.26231},
Abstract = {Habit formation is a behavioral adaptation that automates
routine actions. Habitual behavior correlates with broad
reconfigurations of dorsolateral striatal (DLS) circuit
properties that increase gain and shift pathway timing. The
mechanism(s) for these circuit adaptations are unknown and
could be responsible for habitual behavior. Here we find
that a single class of interneuron, fast-spiking
interneurons (FSIs), modulates all of these habit-predictive
properties. Consistent with a role in habits, FSIs are more
excitable in habitual mice compared to goal-directed and
acute chemogenetic inhibition of FSIs in DLS prevents the
expression of habitual lever pressing. In vivo recordings
further reveal a previously unappreciated selective
modulation of SPNs based on their firing patterns; FSIs
inhibit most SPNs but paradoxically promote the activity of
a subset displaying high fractions of gamma-frequency
spiking. These results establish a microcircuit mechanism
for habits and provide a new example of how interneurons
mediate experience-dependent behavior.},
Doi = {10.7554/eLife.26231},
Key = {fds330155}
}
@article{fds326832,
Author = {Yin, HH},
Title = {The Basal Ganglia in Action.},
Journal = {The Neuroscientist : a review journal bringing neurobiology,
neurology and psychiatry},
Volume = {23},
Number = {3},
Pages = {299-313},
Publisher = {SAGE Publications},
Year = {2017},
Month = {June},
url = {http://dx.doi.org/10.1177/1073858416654115},
Abstract = {The basal ganglia (BG) are the major subcortical nuclei in
the brain. Disorders implicating the BG are characterized by
diverse symptoms, but it remains unclear what these symptoms
have in common or how they can be explained by changes in
the BG circuits. This review summarizes recent findings that
not only question traditional assumptions about the role of
the BG in movement but also elucidate general computations
performed by these circuits. To explain these findings, a
new conceptual framework is introduced for understanding the
role of the BG in behavior. According to this framework, the
cortico-BG networks implement transition control in an
extended hierarchy of closed loop negative feedback control
systems. The transition control model provides a solution to
the posture/movement problem, by postulating that BG outputs
send descending signals to alter the reference states of
downstream position control systems for orientation and body
configuration. It also explains major neurological symptoms
associated with BG pathology as a result of changes in
system parameters such as multiplicative gain and
damping.},
Doi = {10.1177/1073858416654115},
Key = {fds326832}
}
@article{fds330183,
Author = {Wang, X and Bey, AL and Katz, BM and Badea, A and Kim, N and David, LK and Duffney, LJ and Kumar, S and Mague, SD and Hulbert, SW and Dutta, N and Hayrapetyan, V and Yu, C and Gaidis, E and Zhao, S and Ding, J-D and Xu, Q and Chung, L and Rodriguiz, RM and Wang, F and Weinberg, RJ and Wetsel, WC and Dzirasa, K and Yin, H and Jiang, Y-H},
Title = {Altered mGluR5-Homer scaffolds and corticostriatal
connectivity in a Shank3 complete knockout model of
autism.},
Journal = {Nat Commun},
Volume = {7},
Pages = {11459},
Year = {2016},
Month = {May},
url = {http://dx.doi.org/10.1038/ncomms11459},
Abstract = {Human neuroimaging studies suggest that aberrant neural
connectivity underlies behavioural deficits in autism
spectrum disorders (ASDs), but the molecular and neural
circuit mechanisms underlying ASDs remain elusive. Here, we
describe a complete knockout mouse model of the
autism-associated Shank3 gene, with a deletion of exons 4-22
(Δe4-22). Both mGluR5-Homer scaffolds and mGluR5-mediated
signalling are selectively altered in striatal neurons.
These changes are associated with perturbed function at
striatal synapses, abnormal brain morphology, aberrant
structural connectivity and ASD-like behaviour. In vivo
recording reveals that the cortico-striatal-thalamic circuit
is tonically hyperactive in mutants, but becomes hypoactive
during social behaviour. Manipulation of mGluR5 activity
attenuates excessive grooming and instrumental learning
differentially, and rescues impaired striatal synaptic
plasticity in Δe4-22(-/-) mice. These findings show that
deficiency of Shank3 can impair mGluR5-Homer scaffolding,
resulting in cortico-striatal circuit abnormalities that
underlie deficits in learning and ASD-like behaviours. These
data suggest causal links between genetic, molecular, and
circuit mechanisms underlying the pathophysiology of
ASDs.},
Doi = {10.1038/ncomms11459},
Key = {fds330183}
}
@article{fds322207,
Author = {Rossi, MA and Li, HE and Lu, D and Kim, IH and Bartholomew, RA and Gaidis,
E and Barter, JW and Kim, N and Cai, MT and Soderling, SH and Yin,
HH},
Title = {A GABAergic nigrotectal pathway for coordination of drinking
behavior.},
Journal = {Nat Neurosci},
Volume = {19},
Number = {5},
Pages = {742-748},
Year = {2016},
Month = {May},
url = {http://dx.doi.org/10.1038/nn.4285},
Abstract = {The contribution of basal ganglia outputs to consummatory
behavior remains poorly understood. We recorded from the
substantia nigra pars reticulata (SNR), the major basal
ganglia output nucleus, during self-initiated drinking in
mice. The firing rates of many lateral SNR neurons were
time-locked to individual licks. These neurons send
GABAergic projections to the deep layers of the orofacial
region of the lateral tectum (superior colliculus, SC). Many
tectal neurons were also time-locked to licking, but their
activity was usually in antiphase with that of SNR neurons,
suggesting inhibitory nigrotectal projections. We used
optogenetics to selectively activate the GABAergic
nigrotectal afferents in the deep layers of the SC.
Photo-stimulation of the nigrotectal projections transiently
inhibited the activity of the lick-related tectal neurons,
disrupted their licking-related oscillatory pattern and
suppressed self-initiated drinking. These results
demonstrate that GABAergic nigrotectal projections have a
crucial role in coordinating drinking behavior.},
Doi = {10.1038/nn.4285},
Key = {fds322207}
}
@article{fds323501,
Author = {Yin, HH},
Title = {The role of opponent basal ganglia outputs in
behavior},
Journal = {Future Neurology},
Volume = {11},
Number = {2},
Pages = {149-169},
Publisher = {Future Medicine Ltd},
Year = {2016},
Month = {May},
url = {http://dx.doi.org/10.2217/fnl.16.6},
Abstract = {This review is an attempt to explain the role of basal
ganglia (BG) outputs in generating movements. Recent work
showed that opponent outputs from the BG represent
instantaneous body position coordinates during behavior. On
the other hand, projection neurons in the striatum, the
major input nucleus, as well as dopaminergic neurons that
form the nigrostriatal pathway, can represent movement
velocity. To explain these findings, a new model is
proposed, in which the BG implement the level of transition
control in an extended control hierarchy. BG outputs
represent descending reference signals that command diverse
lower-level position controllers. This model not only
explains major neurological symptoms but also makes
quantitative and testable predictions.},
Doi = {10.2217/fnl.16.6},
Key = {fds323501}
}
@article{fds323502,
Author = {Bartholomew, RA and Li, H and Gaidis, EJ and Stackmann, M and Shoemaker,
CT and Rossi, MA and Yin, HH},
Title = {Striatonigral control of movement velocity in
mice.},
Journal = {The European journal of neuroscience},
Volume = {43},
Number = {8},
Pages = {1097-1110},
Year = {2016},
Month = {April},
url = {http://dx.doi.org/10.1111/ejn.13187},
Abstract = {The basal ganglia have long been implicated in action
initiation. Using three-dimensional motion capture, we
quantified the effects of optogenetic stimulation of the
striatonigral (direct) pathway on movement kinematics. We
generated transgenic mice with channelrhodopsin-2 expression
in striatal neurons that express the D1-like dopamine
receptor. With optic fibres placed in the sensorimotor
striatum, an area known to contain movement velocity-related
single units, photo-stimulation reliably produced movements
that could be precisely quantified with our motion capture
programme. A single light pulse was sufficient to elicit
movements with short latencies (< 30 ms). Increasing
stimulation frequency increased movement speed, with a
highly linear relationship. These findings support the
hypothesis that the sensorimotor striatum is part of a
velocity controller that controls rate of change in body
configurations.},
Doi = {10.1111/ejn.13187},
Key = {fds323502}
}
@article{fds330156,
Author = {O'Hare, JK and Ade, KK and Sukharnikova, T and Van Hooser and SD and Palmeri, ML and Yin, HH and Calakos, N},
Title = {Pathway-Specific Striatal Substrates for Habitual
Behavior.},
Journal = {Neuron},
Volume = {89},
Number = {3},
Pages = {472-479},
Year = {2016},
Month = {February},
url = {http://dx.doi.org/10.1016/j.neuron.2015.12.032},
Abstract = {The dorsolateral striatum (DLS) is implicated in habit
formation. However, the DLS circuit mechanisms underlying
habit remain unclear. A key role for DLS is to transform
sensorimotor cortical input into firing of output neurons
that project to the mutually antagonistic direct and
indirect basal ganglia pathways. Here we examine whether
habit alters this input-output function. By imaging
cortically evoked firing in large populations of
pathway-defined striatal projection neurons (SPNs), we
identify features that strongly correlate with habitual
behavior on a subject-by-subject basis. Habitual behavior
correlated with strengthened DLS output to both pathways as
well as a tendency for action-promoting direct pathway SPNs
to fire before indirect pathway SPNs. In contrast, habit
suppression correlated solely with a weakened direct pathway
output. Surprisingly, all effects were broadly distributed
in space. Together, these findings indicate that the
striatum imposes broad, pathway-specific modulations of
incoming activity to render learned motor behaviors
habitual.},
Doi = {10.1016/j.neuron.2015.12.032},
Key = {fds330156}
}
@article{fds323503,
Author = {Berglund, K and Clissold, K and Li, HE and Wen, L and Park, SY and Gleixner, J and Klein, ME and Lu, D and Barter, JW and Rossi, MA and Augustine, GJ and Yin, HH and Hochgeschwender,
U},
Title = {Luminopsins integrate opto- and chemogenetics by using
physical and biological light sources for opsin
activation.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {113},
Number = {3},
Pages = {E358-E367},
Year = {2016},
Month = {January},
url = {http://dx.doi.org/10.1073/pnas.1510899113},
Abstract = {Luminopsins are fusion proteins of luciferase and opsin that
allow interrogation of neuronal circuits at different
temporal and spatial resolutions by choosing either
extrinsic physical or intrinsic biological light for its
activation. Building on previous development of fusions of
wild-type Gaussia luciferase with channelrhodopsin, here we
expanded the utility of luminopsins by fusing bright Gaussia
luciferase variants with either channelrhodopsin to excite
neurons (luminescent opsin, LMO) or a proton pump to inhibit
neurons (inhibitory LMO, iLMO). These improved LMOs could
reliably activate or silence neurons in vitro and in vivo.
Expression of the improved LMO in hippocampal circuits not
only enabled mapping of synaptic activation of CA1 neurons
with fine spatiotemporal resolution but also could drive
rhythmic circuit excitation over a large spatiotemporal
scale. Furthermore, virus-mediated expression of either LMO
or iLMO in the substantia nigra in vivo produced not only
the expected bidirectional control of single unit activity
but also opposing effects on circling behavior in response
to systemic injection of a luciferase substrate. Thus,
although preserving the ability to be activated by external
light sources, LMOs expand the use of optogenetics by making
the same opsins accessible to noninvasive, chemogenetic
control, thereby allowing the same probe to manipulate
neuronal activity over a range of spatial and temporal
scales.},
Doi = {10.1073/pnas.1510899113},
Key = {fds323503}
}
@article{fds336563,
Author = {Koh, S and Kim, N and Yin, HH and Harris, IR and Dejneka, NS and Eroglu,
C},
Title = {Human Umbilical Tissue-Derived Cells Promote Synapse
Formation and Neurite Outgrowth via Thrombospondin Family
Proteins.},
Journal = {J Neurosci},
Volume = {35},
Number = {47},
Pages = {15649-15665},
Year = {2015},
Month = {November},
url = {http://dx.doi.org/10.1523/JNEUROSCI.1364-15.2015},
Abstract = {UNLABELLED: Cell therapy demonstrates great potential for
the treatment of neurological disorders. Human umbilical
tissue-derived cells (hUTCs) were previously shown to have
protective and regenerative effects in animal models of
stroke and retinal degeneration, but the underlying
therapeutic mechanisms are unknown. Because synaptic
dysfunction, synapse loss, degeneration of neuronal
processes, and neuronal death are hallmarks of neurological
diseases and retinal degenerations, we tested whether hUTCs
contribute to tissue repair and regeneration by stimulating
synapse formation, neurite outgrowth, and neuronal survival.
To do so, we used a purified rat retinal ganglion cell
culture system and found that hUTCs secrete factors that
strongly promote excitatory synaptic connectivity and
enhance neuronal survival. Additionally, we demonstrated
that hUTCs support neurite outgrowth under normal culture
conditions and in the presence of the growth-inhibitory
proteins chondroitin sulfate proteoglycan, myelin basic
protein, or Nogo-A (reticulon 4). Furthermore, through
biochemical fractionation and pharmacology, we identified
the major hUTC-secreted synaptogenic factors as the
thrombospondin family proteins (TSPs), TSP1, TSP2, and TSP4.
Silencing TSP expression in hUTCs, using small RNA
interference, eliminated both the synaptogenic function of
these cells and their ability to promote neurite outgrowth.
However, the majority of the prosurvival functions of
hUTC-conditioned media was spared after TSP knockdown,
indicating that hUTCs secrete additional neurotrophic
factors. Together, our findings demonstrate that hUTCs
affect multiple aspects of neuronal health and connectivity
through secreted factors, and each of these paracrine
effects may individually contribute to the therapeutic
function of these cells. SIGNIFICANCE STATEMENT: Human
umbilical tissue-derived cells (hUTC) are currently under
clinical investigation for the treatment of geographic
atrophy secondary to age-related macular degeneration. These
cells show great promise for the treatment of neurological
disorders; however, the therapeutic effects of these cells
on CNS neurons are not fully understood. Here we provide
compelling evidence that hUTCs secrete multiple factors that
work synergistically to enhance synapse formation and
function, and support neuronal growth and survival.
Moreover, we identified thrombospondins (TSPs) as the
hUTC-secreted factors that mediate the synaptogenic and
growth-promoting functions of these cells. Our findings
highlight novel paracrine effects of hUTC on CNS neuron
health and connectivity and begin to unravel potential
therapeutic mechanisms by which these cells elicit their
effects.},
Doi = {10.1523/JNEUROSCI.1364-15.2015},
Key = {fds336563}
}
@article{fds254738,
Author = {Kim, IH and Rossi, MA and Aryal, DK and Racz, B and Kim, N and Uezu, A and Wang, F and Wetsel, WC and Weinberg, RJ and Yin, H and Soderling,
SH},
Title = {Spine pruning drives antipsychotic-sensitive locomotion via
circuit control of striatal dopamine.},
Journal = {Nat Neurosci},
Volume = {18},
Number = {6},
Pages = {883-891},
Year = {2015},
Month = {June},
ISSN = {1097-6256},
url = {http://dx.doi.org/10.1038/nn.4015},
Abstract = {Psychiatric and neurodevelopmental disorders may arise from
anomalies in long-range neuronal connectivity downstream of
pathologies in dendritic spines. However, the mechanisms
that may link spine pathology to circuit abnormalities
relevant to atypical behavior remain unknown. Using a mouse
model to conditionally disrupt a critical regulator of the
dendritic spine cytoskeleton, the actin-related protein 2/3
complex (Arp2/3), we report here a molecular mechanism that
unexpectedly reveals the inter-relationship of progressive
spine pruning, elevated frontal cortical excitation of
pyramidal neurons and striatal hyperdopaminergia in a
cortical-to-midbrain circuit abnormality. The main
symptomatic manifestations of this circuit abnormality are
psychomotor agitation and stereotypical behaviors, which are
relieved by antipsychotics. Moreover, this
antipsychotic-responsive locomotion can be mimicked in
wild-type mice by optogenetic activation of this circuit.
Collectively these results reveal molecular and
neural-circuit mechanisms, illustrating how diverse
pathologies may converge to drive behaviors relevant to
psychiatric disorders.},
Doi = {10.1038/nn.4015},
Key = {fds254738}
}
@article{fds254736,
Author = {Rossi, MA and Yin, HH},
Title = {Elevated dopamine alters consummatory pattern generation and
increases behavioral variability during learning},
Journal = {Frontiers in Integrative Neuroscience},
Volume = {9},
Number = {MAY},
Publisher = {FRONTIERS MEDIA SA},
Year = {2015},
Month = {May},
url = {http://dx.doi.org/10.3389/fnint.2015.00037},
Abstract = {The role of dopamine in controlling behavior remains poorly
understood. In this study we examined licking behavior in an
established hyperdopaminergic mouse model—dopamine
transporter knockout (DAT KO) mice. DAT KO mice showed
higher rates of licking, which is due to increased
perseveration of licking in a bout. By contrast, they showed
increased individual lick durations, and reduced inter-lick
intervals. During extinction, both KO and control mice
transiently increased variability in lick pattern generation
while reducing licking rate, yet they showed very different
behavioral patterns. Control mice gradually increased lick
duration as well as variability. By contrast, DAT KO mice
exhibited more immediate (within 10 licks) adjustments—an
immediate increase in lick duration variability, as well as
more rapid extinction. These results suggest that the level
of dopamine can modulate the persistence and pattern
generation of a highly stereotyped consummatory behavior
like licking, as well as new learning in response to changes
in environmental feedback. Increased dopamine in DAT KO mice
not only increased perseveration of bouts and individual
lick duration, but also increased the behavioral variability
in response to the extinction contingency and the rate of
extinction.},
Doi = {10.3389/fnint.2015.00037},
Key = {fds254736}
}
@article{fds254739,
Author = {Rossi, MA and Calakos, N and Yin, HH},
Title = {Spotlight on movement disorders: What optogenetics has to
offer.},
Journal = {Mov Disord},
Volume = {30},
Number = {5},
Pages = {624-631},
Year = {2015},
Month = {April},
ISSN = {0885-3185},
url = {http://dx.doi.org/10.1002/mds.26184},
Abstract = {Elucidating the neuronal mechanisms underlying movement
disorders is a major challenge because of the intricacy of
the relevant neural circuits, which are characterized by
diverse cell types and complex connectivity. A major
limitation of traditional techniques, such as electrical
stimulation or lesions, is that individual elements of a
neural circuit cannot be selectively manipulated. Moreover,
available treatments are largely based on trial and error
rather than a detailed understanding of the circuit
mechanisms. Gaps in our knowledge of the circuit mechanisms
for movement disorders, as well as mechanisms underlying
known treatments such as deep brain stimulation, make it
difficult to design new and improved treatment options. In
this perspective, we discuss how optogenetics, which allows
researchers to use light to manipulate neuronal activity,
can contribute to the understanding and treatment of
movement disorders. We outline the advantages and
limitations of optogenetics and discuss examples of studies
that have used this tool to clarify the role of the basal
ganglia circuitry in movement.},
Doi = {10.1002/mds.26184},
Key = {fds254739}
}
@article{fds254741,
Author = {Barter, JW and Li, S and Sukharnikova, T and Rossi, MA and Bartholomew,
RA and Yin, HH},
Title = {Basal ganglia outputs map instantaneous position coordinates
during behavior.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {35},
Number = {6},
Pages = {2703-2716},
Year = {2015},
Month = {February},
ISSN = {0270-6474},
url = {http://dx.doi.org/10.1523/jneurosci.3245-14.2015},
Abstract = {The basal ganglia (BG) are implicated in many movement
disorders, yet how they contribute to movement remains
unclear. Using wireless in vivo recording, we measured BG
output from the substantia nigra pars reticulata (SNr) in
mice while monitoring their movements with video tracking.
The firing rate of most nigral neurons reflected Cartesian
coordinates (either x- or y-coordinates) of the animal's
head position during movement. The firing rates of SNr
neurons are either positively or negatively correlated with
the coordinates. Using an egocentric reference frame, four
types of neurons can be classified: each type increases
firing during movement in a particular direction (left,
right, up, down), and decreases firing during movement in
the opposite direction. Given the high correlation between
the firing rate and the x and y components of the position
vector, the movement trajectory can be reconstructed from
neural activity. Our results therefore demonstrate a
quantitative and continuous relationship between BG output
and behavior. Thus, a steady BG output signal from the SNr
(i.e., constant firing rate) is associated with the lack of
overt movement, when a stable posture is maintained by
structures downstream of the BG. Any change in SNr firing
rate is associated with a change in position (i.e.,
movement). We hypothesize that the SNr output quantitatively
determines the direction, velocity, and amplitude of
voluntary movements. By changing the reference signals to
downstream position control systems, the BG can produce
transitions in body configurations and initiate
actions.},
Doi = {10.1523/jneurosci.3245-14.2015},
Key = {fds254741}
}
@article{fds254742,
Author = {Jenkins, PM and Kim, N and Jones, SL and Tseng, WC and Svitkina, TM and Yin, HH and Bennett, V},
Title = {Giant ankyrin-G: a critical innovation in vertebrate
evolution of fast and integrated neuronal
signaling.},
Journal = {Proc Natl Acad Sci U S A},
Volume = {112},
Number = {4},
Pages = {957-964},
Year = {2015},
Month = {January},
ISSN = {0027-8424},
url = {http://dx.doi.org/10.1073/pnas.1416544112},
Abstract = {Axon initial segments (AISs) and nodes of Ranvier are sites
of clustering of voltage-gated sodium channels (VGSCs) in
nervous systems of jawed vertebrates that facilitate fast
long-distance electrical signaling. We demonstrate that
proximal axonal polarity as well as assembly of the AIS and
normal morphogenesis of nodes of Ranvier all require a
heretofore uncharacterized alternatively spliced giant exon
of ankyrin-G (AnkG). This exon has sequence similarity to
I-connectin/Titin and was acquired after the first round of
whole-genome duplication by the ancestral ANK2/ANK3 gene in
early vertebrates before development of myelin. The giant
exon resulted in a new nervous system-specific 480-kDa
polypeptide combining previously known features of ANK
repeats and β-spectrin-binding activity with a fibrous
domain nearly 150 nm in length. We elucidate previously
undescribed functions for giant AnkG, including recruitment
of β4 spectrin to the AIS that likely is regulated by
phosphorylation, and demonstrate that 480-kDa AnkG is a
major component of the AIS membrane "undercoat' imaged by
platinum replica electron microscopy. Surprisingly, giant
AnkG-knockout neurons completely lacking known AIS
components still retain distal axonal polarity and generate
action potentials (APs), although with abnormal frequency.
Giant AnkG-deficient mice live to weaning and provide a
rationale for survival of humans with severe cognitive
dysfunction bearing a truncating mutation in the giant exon.
The giant exon of AnkG is required for assembly of the AIS
and nodes of Ranvier and was a transformative innovation in
evolution of the vertebrate nervous system that now is a
potential target in neurodevelopmental disorders.},
Doi = {10.1073/pnas.1416544112},
Key = {fds254742}
}
@article{fds254735,
Author = {Barter, JW and Li, S and Lu, D and Bartholomew, RA and Rossi, MA and Shoemaker, CT and Salas-Meza, D and Gaidis, E and Yin,
HH},
Title = {Beyond reward prediction errors: the role of dopamine in
movement kinematics.},
Journal = {Frontiers in integrative neuroscience},
Volume = {9},
Number = {MAY},
Pages = {39},
Publisher = {FRONTIERS MEDIA SA},
Year = {2015},
Month = {January},
url = {http://dx.doi.org/10.3389/fnint.2015.00039},
Abstract = {We recorded activity of dopamine (DA) neurons in the
substantia nigra pars compacta in unrestrained mice while
monitoring their movements with video tracking. Our approach
allows an unbiased examination of the continuous
relationship between single unit activity and behavior.
Although DA neurons show characteristic burst firing
following cue or reward presentation, as previously
reported, their activity can be explained by the
representation of actual movement kinematics. Unlike
neighboring pars reticulata GABAergic output neurons, which
can represent vector components of position, DA neurons
represent vector components of velocity or acceleration. We
found neurons related to movements in four directions-up,
down, left, right. For horizontal movements, there is
significant lateralization of neurons: the left nigra
contains more rightward neurons, whereas the right nigra
contains more leftward neurons. The relationship between DA
activity and movement kinematics was found on both
appetitive trials using sucrose and aversive trials using
air puff, showing that these neurons belong to a velocity
control circuit that can be used for any number of purposes,
whether to seek reward or to avoid harm. In support of this
conclusion, mimicry of the phasic activation of DA neurons
with selective optogenetic stimulation could also generate
movements. Contrary to the popular hypothesis that DA
neurons encode reward prediction errors, our results suggest
that nigrostriatal DA plays an essential role in controlling
the kinematics of voluntary movements. We hypothesize that
DA signaling implements gain adjustment for adaptive
transition control, and describe a new model of the basal
ganglia (BG) in which DA functions to adjust the gain of the
transition controller. This model has significant
implications for our understanding of movement disorders
implicating DA and the BG.},
Doi = {10.3389/fnint.2015.00039},
Key = {fds254735}
}
@article{fds254740,
Author = {Rossi, MA and Go, V and Murphy, T and Fu, Q and Morizio, J and Yin,
HH},
Title = {A wirelessly controlled implantable LED system for deep
brain optogenetic stimulation.},
Journal = {Frontiers in integrative neuroscience},
Volume = {9},
Pages = {8},
Year = {2015},
Month = {January},
url = {http://dx.doi.org/10.3389/fnint.2015.00008},
Abstract = {In recent years optogenetics has rapidly become an essential
technique in neuroscience. Its temporal and spatial
specificity, combined with efficacy in manipulating neuronal
activity, are especially useful in studying the behavior of
awake behaving animals. Conventional optogenetics, however,
requires the use of lasers and optic fibers, which can place
considerable restrictions on behavior. Here we combined a
wirelessly controlled interface and small implantable
light-emitting diode (LED) that allows flexible and precise
placement of light source to illuminate any brain area. We
tested this wireless LED system in vivo, in transgenic mice
expressing channelrhodopsin-2 in striatonigral neurons
expressing D1-like dopamine receptors. In all mice tested,
we were able to elicit movements reliably. The frequency of
twitches induced by high power stimulation is proportional
to the frequency of stimulation. At lower power,
contraversive turning was observed. Moreover, the implanted
LED remains effective over 50 days after surgery,
demonstrating the long-term stability of the light source.
Our results show that the wireless LED system can be used to
manipulate neural activity chronically in behaving mice
without impeding natural movements.},
Doi = {10.3389/fnint.2015.00008},
Key = {fds254740}
}
@article{fds336564,
Author = {Kim, N and Barter, JW and Sukharnikova, T and Yin,
HH},
Title = {Striatal firing rate reflects head movement
velocity.},
Journal = {The European journal of neuroscience},
Volume = {40},
Number = {10},
Pages = {3481-3490},
Year = {2014},
Month = {November},
url = {http://dx.doi.org/10.1111/ejn.12722},
Abstract = {Although the basal ganglia have long been implicated in the
initiation of actions, their contribution to movement
remains a matter of dispute. Using wireless multi-electrode
recording and motion tracking, we examined the relationship
between single-unit activity in the sensorimotor striatum
and movement kinematics. We recorded single-unit activity
from medium spiny projection neurons and fast-spiking
interneurons while monitoring the movements of mice using
motion tracking. In Experiment 1, we trained mice to
generate movements reliably by water-depriving them and
giving them periodic cued sucrose rewards. We found high
correlations between single-unit activity and movement
velocity in particular directions. This correlation was
found in both putative medium spiny projection neurons and
fast-spiking interneurons. In Experiment 2, to rule out the
possibility that the observed correlations were due to
reward expectancy, we repeated the same procedure but added
trials in which sucrose delivery was replaced by an aversive
air puff stimulus. The air puff generated avoidance
movements that were clearly different from movements on
rewarded trials, but the same neurons that showed velocity
correlation on reward trials exhibited a similar correlation
on air puff trials. These experiments show for the first
time that the firing rate of striatal neurons reflects
movement velocity for different types of movements, whether
to seek rewards or to avoid harm.},
Doi = {10.1111/ejn.12722},
Key = {fds336564}
}
@article{fds254744,
Author = {McKinstry, SU and Karadeniz, YB and Worthington, AK and Hayrapetyan,
VY and Ozlu, MI and Serafin-Molina, K and Risher, WC and Ustunkaya, T and Dragatsis, I and Zeitlin, S and Yin, HH and Eroglu,
C},
Title = {Huntingtin is required for normal excitatory synapse
development in cortical and striatal circuits.},
Journal = {J Neurosci},
Volume = {34},
Number = {28},
Pages = {9455-9472},
Year = {2014},
Month = {July},
ISSN = {0270-6474},
url = {http://hdl.handle.net/10161/10231 Duke open
access},
Abstract = {Huntington's disease (HD) is a neurodegenerative disease
caused by the expansion of a poly-glutamine (poly-Q) stretch
in the huntingtin (Htt) protein. Gain-of-function effects of
mutant Htt have been extensively investigated as the major
driver of neurodegeneration in HD. However, loss-of-function
effects of poly-Q mutations recently emerged as potential
drivers of disease pathophysiology. Early synaptic problems
in the excitatory cortical and striatal connections have
been reported in HD, but the role of Htt protein in synaptic
connectivity was unknown. Therefore, we investigated the
role of Htt in synaptic connectivity in vivo by
conditionally silencing Htt in the developing mouse cortex.
When cortical Htt function was silenced, cortical and
striatal excitatory synapses formed and matured at an
accelerated pace through postnatal day 21 (P21). This
exuberant synaptic connectivity was lost over time in the
cortex, resulting in the deterioration of synapses by 5
weeks. Synaptic decline in the cortex was accompanied with
layer- and region-specific reactive gliosis without cell
loss. To determine whether the disease-causing poly-Q
mutation in Htt affects synapse development, we next
investigated the synaptic connectivity in a full-length
knock-in mouse model of HD, the zQ175 mouse. Similar to the
cortical conditional knock-outs, we found excessive
excitatory synapse formation and maturation in the cortices
of P21 zQ175, which was lost by 5 weeks. Together, our
findings reveal that cortical Htt is required for the
correct establishment of cortical and striatal excitatory
circuits, and this function of Htt is lost when the mutant
Htt is present.},
Doi = {10.1523/JNEUROSCI.4699-13.2014},
Key = {fds254744}
}
@article{fds254748,
Author = {Leblond, M and Sukharnikova, T and Yu, C and Rossi, MA and Yin,
HH},
Title = {The role of pedunculopontine nucleus in choice behavior
under risk.},
Journal = {The European journal of neuroscience},
Volume = {39},
Number = {10},
Pages = {1664-1670},
Year = {2014},
Month = {May},
ISSN = {0953-816X},
url = {http://dx.doi.org/10.1111/ejn.12529},
Abstract = {The dopaminergic projections to the basal ganglia have long
been implicated in reward-guided behavior and
decision-making, yet little is known about the role of the
posterior pedunculopontine nucleus (pPPN), a major source of
excitatory input to the mesolimbic dopamine system. Here we
studied the contributions of the pPPN to decision-making
under risk, using excitoxic lesions and reversible
inactivation in rats. Rats could choose between two options
- a small but certain reward on one lever; or a large but
uncertain reward on the other lever. The overall payoff
associated with each choice is the same, but the reward
variance (risk) associated with the risky choice is much
higher. In Experiment 1, we showed that excitotoxic lesions
of the pPPN before training did not affect acquisition of
lever pressing. But whereas the controls strongly preferred
the safe choice, the lesioned rats did not. In Experiment 2,
we found that muscimol inactivation of the pPPN also
produced similar effects, but reversibly. These results show
that permanent lesions or reversible inactivation of the
pPPN both abolish risk aversion in decision-making.},
Doi = {10.1111/ejn.12529},
Key = {fds254748}
}
@article{fds254749,
Author = {Barter, JW and Castro, S and Sukharnikova, T and Rossi, MA and Yin,
HH},
Title = {The role of the substantia nigra in posture
control.},
Journal = {The European journal of neuroscience},
Volume = {39},
Number = {9},
Pages = {1465-1473},
Year = {2014},
Month = {May},
ISSN = {0953-816X},
url = {http://dx.doi.org/10.1111/ejn.12540},
Abstract = {Disorders implicating the basal ganglia are often
characterized by postural deficits, but little is known
about the role of the basal ganglia in posture control.
Using wireless multi-electrode recording, we measured single
unit activity from GABAergic and dopaminergic neurons in the
substantia nigra as unrestrained mice stood on an elevated
platform while introducing continuous postural disturbances
in the roll plane. We found two major types of neurons -
those activated by tilt to the left side of the body and
suppressed by tilt to the right side, and others activated
by tilt to the right side and suppressed by tilt to the left
side. Contrary to the prevailing view that the basal ganglia
output from the substantia nigra pars reticulata either
inhibits or disinhibits downstream structures in an all or
none fashion, we showed that it continuously sends
anti-phase signals to their downstream targets. We also
demonstrated for the first time that nigrostriatal
dopaminergic transmission is modulated by postural
disturbances.},
Doi = {10.1111/ejn.12540},
Key = {fds254749}
}
@article{fds254746,
Author = {Hayrapetyan, V and Castro, S and Sukharnikova, T and Yu, C and Cao, X and Jiang, Y-H and Yin, HH},
Title = {Region-specific impairments in striatal synaptic
transmission and impaired instrumental learning in a mouse
model of Angelman syndrome.},
Journal = {The European journal of neuroscience},
Volume = {39},
Number = {6},
Pages = {1018-1025},
Year = {2014},
Month = {March},
ISSN = {0953-816X},
url = {http://dx.doi.org/10.1111/ejn.12442},
Abstract = {Angelman syndrome (AS) is a neurodevelopmental disorder
characterized by mental retardation and impaired speech.
Because patients with this disorder often exhibit motor
tremor and stereotypical behaviors, which are associated
with basal ganglia pathology, we hypothesized that AS is
accompanied by abnormal functioning of the striatum, the
input nucleus of the basal ganglia. Using mutant mice with
maternal deficiency of AS E6-AP ubiquitin protein ligase
Ube3a (Ube3a(m-/p+) ), we assessed the effects of Ube3a
deficiency on instrumental conditioning, a
striatum-dependent task. We used whole-cell patch-clamp
recording to measure glutamatergic transmission in the
dorsomedial striatum (DMS) and dorsolateral striatum (DLS).
Ube3a(m-/p+) mice were severely impaired in initial
acquisition of lever pressing. Whereas the lever pressing of
wild-type controls was reduced by outcome devaluation and
instrumental contingency reversal, the performance of
Ube3a(m-/p+) mice were more habitual, impervious to changes
in outcome value and action-outcome contingency. In the DMS,
but not the DLS, Ube3a(m-/p+) mice showed reduced amplitude
and frequency of miniature excitatory postsynaptic currents.
These results show for the first time a selective deficit in
instrumental conditioning in the Ube3a deficient mouse
model, and suggest a specific impairment in glutmatergic
transmission in the associative corticostriatal circuit in
AS.},
Doi = {10.1111/ejn.12442},
Key = {fds254746}
}
@article{fds254751,
Author = {Yin, HH},
Title = {Action, time and the basal ganglia.},
Journal = {Philosophical transactions of the Royal Society of London.
Series B, Biological sciences},
Volume = {369},
Number = {1637},
Pages = {20120473},
Year = {2014},
Month = {March},
ISSN = {0962-8436},
url = {http://dx.doi.org/10.1098/rstb.2012.0473},
Abstract = {The ability to control the speed of movement is compromised
in neurological disorders involving the basal ganglia, a set
of subcortical cerebral nuclei that receive prominent
dopaminergic projections from the midbrain. For example,
bradykinesia, slowness of movement, is a major symptom of
Parkinson's disease, whereas rapid tics are observed in
patients with Tourette syndrome. Recent experimental work
has also implicated dopamine (DA) and the basal ganglia in
action timing. Here, I advance the hypothesis that the basal
ganglia control the rate of change in kinaesthetic
perceptual variables. In particular, the sensorimotor
cortico-basal ganglia network implements a feedback circuit
for the control of movement velocity. By modulating activity
in this network, DA can change the gain of velocity
reference signals. The lack of DA thus reduces the output of
the velocity control system which specifies the rate of
change in body configurations, slowing the transition from
one body configuration to another.},
Doi = {10.1098/rstb.2012.0473},
Key = {fds254751}
}
@article{fds254745,
Author = {Yin, HH},
Title = {Cortico-Basal Ganglia Networks and the Neural Substrates of
Actions},
Pages = {29-47},
Booktitle = {Neurobiology of alcohol dependence},
Publisher = {Elsevier},
Year = {2014},
Month = {January},
url = {http://dx.doi.org/10.1016/B978-0-12-405941-2.00002-X},
Abstract = {This chapter reviews the mechanisms underlying reward-guided
behavior and their implications for alcohol addiction. It
can be divided into three parts. First, I review recent
innovations in the analysis of goal-directed behavior using
instrumental conditioning procedures and outline a model of
motivated behavior based on hierarchical negative-feedback
control systems. Secondly, I describe the anatomy and
function of the cerebral cortico-basal ganglia networks, the
neural implementations of motivational and motor-control
hierarchies. And finally, I discuss the implications of the
hierarchical model for our understanding of addiction in
general and alcohol addiction in particular. © 2014
Elsevier Inc. All rights reserved.},
Doi = {10.1016/B978-0-12-405941-2.00002-X},
Key = {fds254745}
}
@article{fds254750,
Author = {Leblond, M and Sukharnikova, T and Yu, C and Rossi, MA and Yin,
HH},
Title = {The role of pedunculopontine nucleus in choice behavior
under risk},
Journal = {European Journal of Neuroscience},
Volume = {39},
Number = {10},
Pages = {1664-1670},
Year = {2014},
ISSN = {0953-816X},
url = {http://dx.doi.org/10.1111/ejn.12529},
Doi = {10.1111/ejn.12529},
Key = {fds254750}
}
@article{fds254753,
Author = {Rossi, MA and Fan, D and Barter, JW and Yin, HH},
Title = {Bidirectional modulation of substantia nigra activity by
motivational state.},
Journal = {PloS one},
Volume = {8},
Number = {8},
Pages = {e71598},
Year = {2013},
Month = {January},
ISSN = {1932-6203},
url = {http://dx.doi.org/10.1371/journal.pone.0071598},
Abstract = {A major output nucleus of the basal ganglia is the
substantia nigra pars reticulata, which sends GABAergic
projections to brainstem and thalamic nuclei. The GABAergic
(GABA) neurons are reciprocally connected with nearby
dopaminergic neurons, which project mainly to the basal
ganglia, a set of subcortical nuclei critical for
goal-directed behaviors. Here we examined the impact of
motivational states on the activity of GABA neurons in the
substantia nigra pars reticulata and the neighboring
dopaminergic (DA) neurons in the pars compacta. Both types
of neurons show short-latency bursts to a cue predicting a
food reward. As mice became sated by repeated consumption of
food pellets, one class of neurons reduced cue-elicited
firing, whereas another class of neurons progressively
increased firing. Extinction or pre-feeding just before the
test session dramatically reduced the phasic responses and
their motivational modulation. These results suggest that
signals related to the current motivational state
bidirectionally modulate behavior and the magnitude of
phasic response of both DA and GABA neurons in the
substantia nigra.},
Doi = {10.1371/journal.pone.0071598},
Key = {fds254753}
}
@article{fds254754,
Author = {Rossi, MA and Sukharnikova, T and Hayrapetyan, VY and Yang, L and Yin,
HH},
Title = {Operant self-stimulation of dopamine neurons in the
substantia nigra.},
Journal = {PloS one},
Volume = {8},
Number = {6},
Pages = {e65799},
Year = {2013},
Month = {January},
ISSN = {1932-6203},
url = {http://dx.doi.org/10.1371/journal.pone.0065799},
Abstract = {We examined the contribution of the nigrostriatal DA system
to instrumental learning and behavior using optogenetics in
awake, behaving mice. Using Cre-inducible channelrhodopsin-2
(ChR2) in mice expressing Cre recombinase driven by the
tyrosine hydroxylase promoter (Th-Cre), we tested whether
selective stimulation of DA neurons in the substantia nigra
pars compacta (SNC), in the absence of any natural rewards,
was sufficient to promote instrumental learning in naive
mice. Mice expressing ChR2 in SNC DA neurons readily learned
to press a lever to receive laser stimulation, but unlike
natural food rewards the lever pressing did not decline with
satiation. When the number of presses required to receive a
stimulation was altered, mice adjusted their rate of
pressing accordingly, suggesting that the rate of
stimulation was a controlled variable. Moreover, extinction,
i.e. the cessation of action-contingent stimulation, and the
complete reversal of the relationship between action and
outcome by the imposition of an omission contingency,
rapidly abolished lever pressing. Together these results
suggest that selective activation of SNC DA neurons can be
sufficient for acquisition and maintenance of a new
instrumental action.},
Doi = {10.1371/journal.pone.0065799},
Key = {fds254754}
}
@article{fds254765,
Author = {Barter, JW and Rossi, MA and Yin, HH},
Title = {Waiting for rewards: neural adaptation in substantia nigra
neurons under fixed interval feedback},
Journal = {Journal of neuroscience},
Year = {2013},
Key = {fds254765}
}
@article{fds254763,
Author = {H. Yin and Rossi, MA and Hayrapetyan, VY and Maimon, B and Mak, K and Je, HS and Yin,
HH},
Title = {Prefrontal cortical mechanisms underlying delayed
alternation in mice.},
Journal = {Journal of neurophysiology},
Volume = {108},
Number = {4},
Pages = {1211-1222},
Year = {2012},
Month = {August},
ISSN = {0022-3077},
url = {http://dx.doi.org/10.1152/jn.01060.2011},
Abstract = {The prefrontal cortex (PFC) has been implicated in the
maintenance of task-relevant information during
goal-directed behavior. Using a combination of lesions,
local inactivation, and optogenetics, we investigated the
functional role of the medial prefrontal cortex (mPFC) in
mice with a novel operant delayed alternation task. Task
difficulty was manipulated by changing the duration of the
delay between two sequential actions. In experiment 1, we
showed that excitotoxic lesions of the mPFC impaired
acquisition of delayed alternation with long delays (16 s),
whereas lesions of the dorsal hippocampus and ventral
striatum, areas connected with the PFC, did not produce any
deficits. Lesions of dorsal hippocampus, however,
significantly impaired reversal learning when the rule was
changed from alternation to repetition. In experiment 2, we
showed that local infusions of muscimol (an agonist of the
GABA(A) receptor) into mPFC impaired performance even when
the animal was well trained, suggesting that the mPFC is
critical not only for acquisition but also for successful
performance. In experiment 3, to examine the mechanisms
underlying the role of GABAergic inhibition, we used
Cre-inducible Channelrhodopsin-2 to activate parvalbumin
(PV)-expressing GABAergic interneurons in the mPFC of PV-Cre
transgenic mice as they performed the task. Using whole cell
patch-clamp recording, we demonstrated that activation of
PV-expressing interneurons in vitro with blue light in brain
slices reliably produced spiking and inhibited nearby
pyramidal projection neurons. With similar stimulation
parameters, in vivo stimulation significantly impaired
delayed alternation performance. Together these results
demonstrate a critical role for the mPFC in the acquisition
and performance of the delayed alternation
task.},
Doi = {10.1152/jn.01060.2011},
Key = {fds254763}
}
@article{fds254764,
Author = {H. Yin and Rossi, MA},
Title = {Methods for studying habitual behavior in
mice},
Journal = {Current protocols in neuroscience},
Volume = {Chapter 8},
Pages = {Unit-8.29},
Year = {2012},
Month = {July},
url = {http://dx.doi.org/10.1002/0471142301.ns0829s60},
Abstract = {Habit formation refers to the process by which goal-directed
behavior becomes automatized and less sensitive to changes
in the value of the goal. It has clear relevance for our
understanding of skill learning and addiction. Recent
studies have begun to reveal the neural substrates
underlying this process. This unit summarizes what is known
about the experimental methods used, and provides a protocol
for generating and assessing habit formation in
mice.},
Doi = {10.1002/0471142301.ns0829s60},
Key = {fds254764}
}
@article{fds318801,
Author = {Fan, D and Rossi, MA and Yin, HH},
Title = {Mechanisms of action selection and timing in substantia
nigra neurons.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {32},
Number = {16},
Pages = {5534-5548},
Year = {2012},
Month = {April},
url = {http://dx.doi.org/10.1523/jneurosci.5924-11.2012},
Abstract = {The timing of actions is critical for adaptive behavior. In
this study we measured neural activity in the substantia
nigra as mice learned to change their action duration to
earn food rewards. We observed dramatic changes in single
unit activity during learning: both dopaminergic and
GABAergic neurons changed their activity in relation to
behavior to reflect the learned instrumental contingency and
the action duration. We found the emergence of "action-on"
neurons that increased firing for the duration of the lever
press and mirror-image "action-off" neurons that paused at
the same time. This pattern is especially common among
GABAergic neurons. The activity of many neurons also
reflected confidence about the just completed action and the
prospect of reward. Being correlated with the relative
duration of the completed action, their activity could
predict the likelihood of reward collection. Compared with
the GABAergic neurons, the activity of dopaminergic neurons
was more commonly modulated by the discriminative stimulus
signaling the start of each trial, suggesting that their
phasic activity reflected sensory salience rather than any
reward prediction error found in previous work. In short,
these results suggest that (1) nigral activity is highly
plastic and modified by the learning of the instrumental
contingency; (2) GABAergic output from the substantia nigra
can simultaneously inhibit and disinhibit downstream
structures, while the dopaminergic output also provide
bidirectional modulation of the corticostriatal circuits;
(3) dopaminergic and GABAergic neurons show similar
task-related activity, although DA neurons are more
responsive to the trial start signal.},
Doi = {10.1523/jneurosci.5924-11.2012},
Key = {fds318801}
}
@article{fds254766,
Author = {H. Yin and Yu, C and Fan, D and Lopez, A and Yin, HH},
Title = {Dynamic changes in single unit activity and γ oscillations
in a thalamocortical circuit during rapid instrumental
learning.},
Journal = {PloS one},
Volume = {7},
Number = {11},
Pages = {e50578},
Year = {2012},
Month = {January},
ISSN = {1932-6203},
url = {http://dx.doi.org/10.1371/journal.pone.0050578},
Abstract = {The medial prefrontal cortex (mPFC) and mediodorsal thalamus
(MD) together form a thalamocortical circuit that has been
implicated in the learning and production of goal-directed
actions. In this study we measured neural activity in both
regions simultaneously, as rats learned to press a lever to
earn food rewards. In both MD and mPFC, instrumental
learning was accompanied by dramatic changes in the firing
patterns of the neurons, in particular the rapid emergence
of single-unit neural activity reflecting the completion of
the action and reward delivery. In addition, we observed
distinct patterns of changes in the oscillatory LFP response
in MD and mPFC. With learning, there was a significant
increase in theta band oscillations (6-10 Hz) in the MD, but
not in the mPFC. By contrast, gamma band oscillations (40-55
Hz) increased in the mPFC, but not in the MD. Coherence
between these two regions also changed with learning: gamma
coherence in relation to reward delivery increased, whereas
theta coherence did not. Together these results suggest
that, as rats learned the instrumental contingency between
action and outcome, the emergence of task related neural
activity is accompanied by enhanced functional interaction
between MD and mPFC in response to the reward
feedback.},
Doi = {10.1371/journal.pone.0050578},
Key = {fds254766}
}
@article{fds254762,
Author = {Barter, JW and Castro, S and Sukharnikova, T and Rossi, MA and Ebenstein, W},
Title = {The role of the substantia nigra in posture
control},
Journal = {Journal of neuroscience},
Year = {2012},
Key = {fds254762}
}
@article{fds254767,
Author = {H. Yin and Rossi, MA and Fan, D},
Title = {Mechanisms of action selection and timing in substantia
nigra neurons.},
Journal = {Journal of neuroscience},
Volume = {2},
Number = {16},
Pages = {5534-5548},
Year = {2012},
ISSN = {0270-6474},
url = {http://dx.doi.org/10.1523/jneurosci.5924-11.2012},
Abstract = {The timing of actions is critical for adaptive behavior. In
this study we measured neural activity in the substantia
nigra as mice learned to change their action duration to
earn food rewards. We observed dramatic changes in single
unit activity during learning: both dopaminergic and
GABAergic neurons changed their activity in relation to
behavior to reflect the learned instrumental contingency and
the action duration. We found the emergence of "action-on"
neurons that increased firing for the duration of the lever
press and mirrorimage "action-off" neurons that paused at
the same time. This pattern is especially common among
GABAergic neurons. The activity of many neurons also
reflected confidence about the just completed action and the
prospect of reward. Being correlated with the relative
duration of the completed action, their activity could
predict the likelihood of reward collection. Compared with
the GABAergic neurons, the activity of dopaminergic neurons
was more commonly modulated by the discriminative stimulus
signaling the start of each trial, suggesting that their
phasic activity reflected sensory salience rather than any
reward prediction error found in previous work. In short,
these results suggest that (1) nigral activity is highly
plastic and modified by the learning of the instrumental
contingency; (2) GABAergic output from the substantia nigra
can simultaneously inhibit and disinhibit downstream
structures, while the dopaminergic output also provide
bidirectional modulation of the corticostriatal circuits;
(3) dopaminergic and GABAergic neurons show similar
task-related activity, although DA neurons are more
responsive to the trial start signal. © 2012 the
authors.},
Doi = {10.1523/jneurosci.5924-11.2012},
Key = {fds254767}
}
@article{fds254760,
Author = {Rossi, MA and Yin, HH},
Title = {The role of the dorsal striatum in instrumental
conditioning},
Journal = {Neuromethods},
Volume = {62},
Pages = {55-69},
Publisher = {Humana Press},
Year = {2011},
Month = {October},
ISSN = {0893-2336},
url = {http://dx.doi.org/10.1007/978-1-61779-301-1_4},
Abstract = {This chapter is divided into three parts. In the first part,
we introduce the theoretical foundation of instrumental
conditioning and the commonly used methods to study it. In
the second part, we review some recent work using these
methods to investigate the role of the dorsal striatum in
instrumental conditioning. In the third part, we describe in
detail the methods and considerations in defining precise
and informative experiments in operant analysis of striatal
function. © 2011 Springer Science+Business Media,
LLC.},
Doi = {10.1007/978-1-61779-301-1_4},
Key = {fds254760}
}
@article{fds254768,
Author = {Leblond, M and Fan, D and Brynildsen, JK and Yin,
HH},
Title = {Motivational state and reward content determine choice
behavior under risk in mice.},
Journal = {PloS one},
Volume = {6},
Number = {9},
Pages = {e25342},
Year = {2011},
Month = {January},
ISSN = {1932-6203},
url = {http://dx.doi.org/10.1371/journal.pone.0025342},
Abstract = {Risk is a ubiquitous feature of the environment for most
organisms, who must often choose between a small and certain
reward and a larger but less certain reward. To study choice
behavior under risk in a genetically well characterized
species, we trained mice (C57BL/6) on a discrete trial,
concurrent-choice task in which they must choose between two
levers. Pressing one lever (safe choice) is always followed
by a small reward. Pressing the other lever (risky choice)
is followed by a larger reward, but only on some of the
trials. The overall payoff is the same on both levers. When
mice were not food deprived, they were indifferent to risk,
choosing both levers with equal probability regardless of
the level of risk. In contrast, following food or water
deprivation, mice earning 10% sucrose solution were
risk-averse, though the addition of alcohol to the sucrose
solution dose-dependently reduced risk aversion, even before
the mice became intoxicated. Our results falsify the budget
rule in optimal foraging theory often used to explain
behavior under risk. Instead, they suggest that the overall
demand or desired amount for a particular reward determines
risk preference. Changes in motivational state or reward
identity affect risk preference by changing demand. Any
manipulation that increases the demand for a reward also
increases risk aversion, by selectively increasing the
frequency of safe choices without affecting frequency of
risky choices.},
Doi = {10.1371/journal.pone.0025342},
Key = {fds254768}
}
@article{fds254769,
Author = {Fan, D and Rich, D and Holtzman, T and Ruther, P and Dalley, JW and Lopez,
A and Rossi, MA and Barter, JW and Salas-Meza, D and Herwik, S and Holzhammer, T and Morizio, J and Yin, HH},
Title = {A wireless multi-channel recording system for freely
behaving mice and rats.},
Journal = {PloS one},
Volume = {6},
Number = {7},
Pages = {e22033},
Year = {2011},
Month = {January},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21765934},
Abstract = {To understand the neural basis of behavior, it is necessary
to record brain activity in freely moving animals. Advances
in implantable multi-electrode array technology have enabled
researchers to record the activity of neuronal ensembles
from multiple brain regions. The full potential of this
approach is currently limited by reliance on cable tethers,
with bundles of wires connecting the implanted electrodes to
the data acquisition system while impeding the natural
behavior of the animal. To overcome these limitations, here
we introduce a multi-channel wireless headstage system
designed for small animals such as rats and mice. A variety
of single unit and local field potential signals were
recorded from the dorsal striatum and substantia nigra in
mice and the ventral striatum and prefrontal cortex
simultaneously in rats. This wireless system could be
interfaced with commercially available data acquisition
systems, and the signals obtained were comparable in quality
to those acquired using cable tethers. On account of its
small size, light weight, and rechargeable battery, this
wireless headstage system is suitable for studying the
neural basis of natural behavior, eliminating the need for
wires, commutators, and other limitations associated with
traditional tethered recording systems.},
Doi = {10.1371/journal.pone.0022033},
Key = {fds254769}
}
@article{fds254772,
Author = {de Russo, AL and Fan, D and Gupta, J and Shelest, O and Costa, RM and Yin,
HH},
Title = {Instrumental uncertainty as a determinant of behavior under
interval schedules of reinforcement},
Journal = {Frontiers in Integrative Neuroscience},
Volume = {4},
Number = {MAY 2010},
Year = {2010},
Month = {December},
ISSN = {1662-5145},
url = {http://dx.doi.org/10.3389/fnint.2010.00017},
Abstract = {Interval schedules of reinforcement are known to generate
habitual behavior, the performance of which is less
sensitive to revaluation of the earned reward and to
alterations in the action-outcome contingency. Here we
report results from experiments using different types of
interval schedules of reinforcement in mice to assess the
effect of uncertainty, in the time of reward availability,
on habit formation. After limited training, lever pressing
under fixed interval (FI, low interval uncertainty) or
random interval schedules (RI, higher interval uncertainty)
was sensitive to devaluation, but with more extended
training, performance of animals trained under RI schedules
became more habitual, i.e. no longer sensitive to
devaluation, whereas performance of those trained under FI
schedules remained goal-directed. When the press-reward
contingency was reversed by omitting reward after pressing
but presenting reward in the absence of pressing, lever
pressing in mice previously trained under FI decreased more
rapidly than that of mice trained under RI schedules.
Further analysis revealed that action-reward contiguity is
significantly reduced in lever pressing under RI schedules,
whereas action-reward correlation is similar for the
different schedules. Thus the extent of goal-directedness
could vary as a function of uncertainty about the time of
reward availability. We hypothesize that the reduced
action-reward contiguity found in behavior generated under
high uncertainty is responsible for habit formation. © 2010
DeRusso, Fan, Gupta, Shelest, Costa and Yin.},
Doi = {10.3389/fnint.2010.00017},
Key = {fds254772}
}
@article{fds254770,
Author = {Yin, HH},
Title = {The sensorimotor striatum is necessary for serial order
learning.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {30},
Number = {44},
Pages = {14719-14723},
Year = {2010},
Month = {November},
ISSN = {0270-6474},
url = {http://dx.doi.org/10.1523/jneurosci.3989-10.2010},
Abstract = {Central to the production of adaptive behavior is the
ability to learn the temporal order of behavioral elements
(e.g., A, B, C). Yet little is known about neural substrates
of serial order in self-initiated behavioral sequences. The
present study assessed the contributions of specific dorsal
striatal regions to the acquisition of serial order in mice,
using a two-action sequence task without instructive cues.
Excitotoxic lesions of the sensorimotor (dorsolateral)
striatum dramatically impaired the acquisition of a simple
sequence; in contrast, lesions of the associative
(dorsomedial) striatum had no significant effect. Neither
lesion caused gross motor impairments or affected the
learning of nonsequential actions. These results demonstrate
for the first time a critical role of the sensorimotor
striatum in the learning of serial order.},
Doi = {10.1523/jneurosci.3989-10.2010},
Key = {fds254770}
}
@article{fds254771,
Author = {YU, C and Gupta, J and Yin, HH},
Title = {The role of mediodorsal thalamus in temporal differentiation
of reward-guided actions},
Journal = {Frontiers in Integrative Neuroscience},
Volume = {4},
Number = {MAY 2010},
Publisher = {FRONTIERS MEDIA SA},
Year = {2010},
Month = {May},
ISSN = {1662-5145},
url = {http://dx.doi.org/10.3389/fnint.2010.00014},
Abstract = {The mediodorsal thalamus (MD) is a crucial component of the
neural network involved in the learning and generation of
goal-directed actions. A series of experiments reported here
examined the contributions of MD to the temporal
differentiation of reward-guided actions. In Experiment 1,
we trained rats on a discrete-trial, fixed-criterion
temporal differentiation task, in which only lever presses
exceeding a threshold duration value were rewarded.
Pre-training MD lesions impaired temporal differentiation of
action duration, by increasing the dispersion of the
duration distribution. Post-training MD lesions also
impaired differentiation, but by reducing the average
emitted press durations, thus shifting the distribution
without increasing the dispersion. In Experiment 2, we
trained rats to space their lever pressing above criterion
inter-press-intervals in order to earn rewards. Both
pre-training and post-training MD lesions impaired the
differentiation of inter-press-intervals. These results show
that MD plays an important role in the acquisition and
expression of action differentiation.},
Doi = {10.3389/fnint.2010.00014},
Key = {fds254771}
}
@article{fds340934,
Author = {DeRusso, AL and Fan, D and Gupta, J and Shelest, O and Costa, RM and Yin,
HH},
Title = {Instrumental uncertainty as a determinant of behavior under
interval schedules of reinforcement},
Journal = {Frontiers in Integrative Neuroscience},
Number = {MAY 2010},
Year = {2010},
Key = {fds340934}
}
@article{fds254775,
Author = {Yu, C and Gupta, J and Chen, JF and Yin, HH},
Title = {Genetic deletion of A2A adenosine receptors in the striatum
selectively impairs habit formation},
Journal = {Journal of Neuroscience},
Volume = {29},
Number = {48},
Pages = {15100-15103},
Year = {2009},
Month = {December},
ISSN = {0270-6474},
url = {http://dx.doi.org/10.1523/jneurosci.4215-09.2009},
Abstract = {A(2A) receptors are a major class of G-protein-coupled
receptors for adenosine. Highly expressed in the striatum,
on the projection neurons giving rise to the striatopallidal
or "indirect" pathway, they have been implicated in sleep,
addiction, and other processes, yet their role in the
control of striatal circuits and behavior remains unclear.
Using established assays from the instrumental learning
paradigm, we showed that mice with striatum-specific
deletion of A(2A) receptors were selectively impaired in
habit formation. After training that generated habitual
lever pressing in wild-type controls, the performance of
striatum-specific A(2A) knock-out mice remained goal
directed, being highly sensitive to outcome devaluation and
reversal of the action-outcome contingency. These data
demonstrate a critical role for A(2A) receptors on
striatopallidal medium spiny projection neurons in shaping
behavior and decision making, providing the first instance
of a selective alteration in instrumental learning after
striatum-specific genetic manipulations.},
Doi = {10.1523/jneurosci.4215-09.2009},
Key = {fds254775}
}
@article{fds304757,
Author = {Yin, HH},
Title = {The role of the murine motor cortex in action duration and
order},
Journal = {Frontiers in Integrative Neuroscience},
Volume = {3},
Number = {OCT},
Publisher = {FRONTIERS MEDIA SA},
Year = {2009},
Month = {October},
ISSN = {1662-5145},
url = {http://dx.doi.org/10.3389/neuro.07.023.2009},
Abstract = {This study examined the contributions of the primary and
secondary motor cortices (M1 and M2) to action
differentiation and sequencing in mice. In Experiment 1,
mice with excitotoxic lesions of M1 and M2 and sham controls
learned to emit lever presses exceeding a criterion duration
to earn food rewards. Duration differentiation obeys Weber's
law - i.e. the spread of the distribution is proportional to
the average duration. M1 or M2 lesions did not affect
differentiation of press durations. Experiment 2 studied the
effects of the same lesions on the learning of a simple
sequence consisting of two lever presses, one distal, and
the other proximal, to the reward. M2 lesions impaired the
acquisition and reversal of this sequence. M1 lesions, by
contrast, had no effect on acquisition but impaired sequence
reversal. Moreover, duration of the first press in a
sequence was on average twice as long as that of the second
press, though this ratio was not affected by motor cortex
lesions. Together these results offer a first glimpse into
the cortical substrates of instrumental differentiation in
mice. © 2009 Yin.},
Doi = {10.3389/neuro.07.023.2009},
Key = {fds304757}
}
@article{fds254774,
Author = {Yin, HH},
Title = {The role of the murine motor cortex in action duration and
order},
Journal = {Frontiers in integrative neuroscience},
Volume = {3},
Number = {23},
Year = {2009},
Month = {October},
ISSN = {1662-5145},
url = {http://dx.doi.org/10.3389/neuro.07.023.2009},
Abstract = {This study examined the contributions of the primary and
secondary motor cortices (M1 and M2) to action
differentiation and sequencing in mice. In Experiment 1,
mice with excitotoxic lesions of M1 and M2 and sham controls
learned to emit lever presses exceeding a criterion duration
to earn food rewards. Duration differentiation obeys Weber's
law - i.e. the spread of the distribution is proportional to
the average duration. M1 or M2 lesions did not affect
differentiation of press durations. Experiment 2 studied the
effects of the same lesions on the learning of a simple
sequence consisting of two lever presses, one distal, and
the other proximal, to the reward. M2 lesions impaired the
acquisition and reversal of this sequence. M1 lesions, by
contrast, had no effect on acquisition but impaired sequence
reversal. Moreover, duration of the first press in a
sequence was on average twice as long as that of the second
press, though this ratio was not affected by motor cortex
lesions. Together these results offer a first glimpse into
the cortical substrates of instrumental differentiation in
mice. © 2009 Yin.},
Doi = {10.3389/neuro.07.023.2009},
Key = {fds254774}
}
@article{fds304758,
Author = {Yin, H},
Title = {From actions to habits},
Journal = {Alcohol Research and Health},
Volume = {31},
Number = {4},
Pages = {340-344},
Year = {2009},
Month = {May},
ISSN = {1535-7414},
Abstract = {Recent work on the role of overlapping cerebral networks in
action selection and habit formation has important
implications for alcohol addiction research. As reviewed
below, (1) these networks, which all involve a group of
deep-brain structures called the basal ganglia, are
associated with distinct behavioral control processes, such
as reward-guided Pavlovian conditional responses,
goal-directed instrumental actions, and stimulus-driven
habits; (2) different stages of action learning are
associated with different networks, which have the ability
to change (i.e., plasticity); and (3) exposure to alcohol
and other addictive drugs can have profound effects on these
networks by influencing the mechanisms underlying neural
plasticity.},
Key = {fds304758}
}
@article{fds254776,
Author = {Yin, HH and Mulcare, SP and Hilário, MRF and Clouse, E and Holloway, T and Davis, MI and Hansson, AC and Lovinger, DM and Costa,
RM},
Title = {Dynamic reorganization of striatal circuits during the
acquisition and consolidation of a skill.},
Journal = {Nature neuroscience},
Volume = {12},
Number = {3},
Pages = {333-341},
Year = {2009},
Month = {March},
ISSN = {1097-6256},
url = {http://dx.doi.org/10.1038/nn.2261},
Abstract = {The learning of new skills is characterized by an initial
phase of rapid improvement in performance and a phase of
more gradual improvements as skills are automatized and
performance asymptotes. Using in vivo striatal recordings,
we observed region-specific changes in neural activity
during the different phases of skill learning, with the
associative or dorsomedial striatum being preferentially
engaged early in training and the sensorimotor or
dorsolateral striatum being engaged later in training. Ex
vivo recordings from medium spiny striatal neurons in brain
slices of trained mice revealed that the changes observed in
vivo corresponded to regional- and training-specific changes
in excitatory synaptic transmission in the striatum.
Furthermore, the potentiation of glutamatergic transmission
observed in dorsolateral striatum after extensive training
was preferentially expressed in striatopallidal neurons,
rather than striatonigral neurons. These findings
demonstrate that region- and pathway-specific plasticity
sculpts the circuits involved in the performance of the
skill as it becomes automatized.},
Doi = {10.1038/nn.2261},
Key = {fds254776}
}
@article{fds254773,
Author = {Yin, HH},
Title = {Neuroadaptations leading to alcohol addiction and
dependence.},
Journal = {Alcohol Research and Health},
Volume = {31},
Number = {4},
Pages = {340-344},
Year = {2009},
ISSN = {1535-7414},
Abstract = {Recent work on the role of overlapping cerebral networks in
action selection and habit formation has important
implications for alcohol addiction research. As reviewed
below, (1) these networks, which all involve a group of
deep-brain structures called the basal ganglia, are
associated with distinct behavioral control processes, such
as reward-guided Pavlovian conditional responses,
goal-directed instrumental actions, and stimulus-driven
habits; (2) different stages of action learning are
associated with different networks, which have the ability
to change (i.e., plasticity); and (3) exposure to alcohol
and other addictive drugs can have profound effects on these
networks by influencing the mechanisms underlying neural
plasticity.},
Key = {fds254773}
}
@article{fds254777,
Author = {Yin, HH and Ostlund, SB and Balleine, BW},
Title = {Reward-guided learning beyond dopamine in the nucleus
accumbens: the integrative functions of cortico-basal
ganglia networks.},
Journal = {The European journal of neuroscience},
Volume = {28},
Number = {8},
Pages = {1437-1448},
Year = {2008},
Month = {October},
ISSN = {0953-816X},
url = {http://dx.doi.org/10.1111/j.1460-9568.2008.06422.x},
Abstract = {Here we challenge the view that reward-guided learning is
solely controlled by the mesoaccumbens pathway arising from
dopaminergic neurons in the ventral tegmental area and
projecting to the nucleus accumbens. This widely accepted
view assumes that reward is a monolithic concept, but recent
work has suggested otherwise. It now appears that, in
reward-guided learning, the functions of ventral and dorsal
striata, and the cortico-basal ganglia circuitry associated
with them, can be dissociated. Whereas the nucleus accumbens
is necessary for the acquisition and expression of certain
appetitive Pavlovian responses and contributes to the
motivational control of instrumental performance, the dorsal
striatum is necessary for the acquisition and expression of
instrumental actions. Such findings suggest the existence of
multiple independent yet interacting functional systems that
are implemented in iterating and hierarchically organized
cortico-basal ganglia networks engaged in appetitive
behaviors ranging from Pavlovian approach responses to
goal-directed instrumental actions controlled by
action-outcome contingencies.},
Doi = {10.1111/j.1460-9568.2008.06422.x},
Key = {fds254777}
}
@article{fds254757,
Author = {Yin, H},
Title = {The elephantine shape of addiction},
Journal = {Behavioral and Brain Sciences},
Volume = {31},
Number = {4},
Pages = {461},
Publisher = {Cambridge University Press (CUP)},
Year = {2008},
Month = {August},
ISSN = {0140-525X},
url = {http://dx.doi.org/10.1017/S0140525X08004974},
Abstract = {By summarizing, in a single piece, various current
perspectives on addiction, Redish et al. have performed a
useful service to the field. Their central message is that
addiction comprises many vulnerabilities rather than a
single vulnerability. Such a message may not be new, but it
is worth repeating. © 2008 Cambridge University
Press.},
Doi = {10.1017/S0140525X08004974},
Key = {fds254757}
}
@article{fds254734,
Author = {Yin, HH},
Title = {From actions to habits: neuroadaptations leading to
dependence.},
Journal = {Alcohol research & health : the journal of the National
Institute on Alcohol Abuse and Alcoholism},
Volume = {31},
Number = {4},
Pages = {340-344},
Year = {2008},
Month = {January},
ISSN = {1535-7414},
Abstract = {Recent work on the role of overlapping cerebral networks in
action selection and habit formation has important
implications for alcohol addiction research. As reviewed
below, (1) these networks, which all involve a group of
deep-brain structures called the basal ganglia, are
associated with distinct behavioral control processes, such
as reward-guided Pavlovian conditional responses,
goal-directed instrumental actions, and stimulus-driven
habits; (2) different stages of action learning are
associated with different networks, which have the ability
to change (i.e., plasticity); and (3) exposure to alcohol
and other addictive drugs can have profound effects on these
networks by influencing the mechanisms underlying neural
plasticity.},
Key = {fds254734}
}
@article{fds254778,
Author = {Yin, HH and Adermark, L and Lovinger, DM},
Title = {Neurotensin reduces glutamatergic transmission in the
dorsolateral striatum via retrograde endocannabinoid
signaling.},
Journal = {Neuropharmacology},
Volume = {54},
Number = {1},
Pages = {79-86},
Year = {2008},
Month = {January},
ISSN = {0028-3908},
url = {http://dx.doi.org/10.1016/j.neuropharm.2007.06.004},
Abstract = {Neurotensin is a peptide that has been suggested to mimic
the actions of antipsychotics, but little is known about how
it affects synaptic transmission in the striatum, the major
input nucleus of the basal ganglia. In this study we
measured the effects of neurotensin on EPSCs from medium
spiny projection neurons in the sensorimotor striatum, a
region implicated in habit formation and control of motor
sequences. We found that bath-applied neurotensin reduced
glutamate release from presynaptic terminals, and that this
effect required retrograde endocannabinoid signaling, as it
was prevented by the CB1 cannabinoid receptor antagonist
AM251. Neurotensin-mediated inhibition of striatal EPSCs was
also blocked by antagonists of D2-like dopamine receptors
and group I metabotropic glutamate receptors, as well as by
intracellular calcium chelation and phospholipase C
inhibition. These results suggest that neurotensin can
indirectly engage an endocannabinoid-mediated negative
feedback signal to control glutamatergic input to the basal
ganglia.},
Doi = {10.1016/j.neuropharm.2007.06.004},
Key = {fds254778}
}
@article{fds254747,
Author = {Hilário, MRF and Clouse, E and Yin, HH and Costa,
RM},
Title = {Endocannabinoid signaling is critical for habit
formation},
Journal = {Frontiers in Integrative Neuroscience},
Volume = {1},
Number = {NOV},
Publisher = {FRONTIERS MEDIA SA},
Year = {2007},
Month = {November},
url = {http://dx.doi.org/10.3389/neuro.07.006.2007},
Abstract = {Extended training can induce a shift in behavioral control
from goal-directed actions, which are governed by
action-outcome contingencies and sensitive to change in the
expected value of the outcome, to habits which are less
dependent on action-outcome relations and insensitive to
changes in outcome value. Previous studies in rats have
shown that interval schedules of reinforcement favor habit
formation while ratio schedules favor goal-directed
behavior. However, the molecular mechanisms underlying habit
formation are not well understood. Endocannabinoids, which
can function as retrograde messengers acting through
presynaptic CB1 receptors, are highly expressed in the
dorsolateral striatum, a key region involved in habit
formation. Using a reversible devaluation paradigm, we
confirmed that in mice random interval schedules also favor
habit formation compared with random ratio schedules. We
also found that training with interval schedules resulted in
a preference for exploration of a novel lever, whereas
training with ratio schedules resulted in less
generalization and more exploitation of the reinforced
lever. Furthermore, mice carrying either a heterozygous or a
homozygous null mutation of the cannabinoid receptor type I
(CB1) showed reduced habit formation and enhanced
exploitation. The impaired habit formation in CB1 mutant
mice cannot be attributed to chronic developmental or
behavioral abnormalities because pharmacological blockade of
CB1 receptors specifically during training also impairs
habit formation. Taken together our data suggest that
endocannabinoid signaling is critical for habit formation.
© 2007 Hilário, Clouse, Yin, Costa.},
Doi = {10.3389/neuro.07.006.2007},
Key = {fds254747}
}
@article{fds254782,
Author = {Yin, HH and Park, BS and Adermark, L and Lovinger,
DM},
Title = {Ethanol reverses the direction of long-term synaptic
plasticity in the dorsomedial striatum.},
Journal = {The European journal of neuroscience},
Volume = {25},
Number = {11},
Pages = {3226-3232},
Year = {2007},
Month = {June},
ISSN = {0953-816X},
url = {http://dx.doi.org/10.1111/j.1460-9568.2007.05606.x},
Abstract = {The striatum is a critical structure for the control of
voluntary behaviour, and striatal synaptic plasticity has
been implicated in instrumental learning. As ethanol
consumption can cause impairments in cognition, learning,
and action selection, it is important to understand the
effects of this drug on striatal function. In this study we
examined the effects of ethanol on long-term synaptic
plasticity in the dorsomedial striatum (DMS), a striatal
subregion that plays a central role in the acquisition and
selection of goal-directed actions. Ethanol was found to
impair N-methyl-d-aspartic acid receptor (NMDAR)-dependent
long-term potentiation (LTP) dose-dependently in the DMS,
and to promote long-term depression (LTD) at the highest
concentration (50 mm) used. These results suggest that
ethanol, at a concentration usually associated with mild
intoxication, could significantly change
experience-dependent modification of corticostriatal
circuits underlying the learning of goal-directed
instrumental actions.},
Doi = {10.1111/j.1460-9568.2007.05606.x},
Key = {fds254782}
}
@article{fds254779,
Author = {Hilario, M and Clouse, E and Yin, HH and Costa, RM},
Title = {Endocannabinoid signaling is required for habit
formation},
Journal = {Frontiers in Integrative Neuroscience},
Volume = {1(6)},
Number = {NOV},
Year = {2007},
url = {http://dx.doi.org/10.3389/neuro.07/006.2007},
Abstract = {Extended training can induce a shift in behavioral control
from goal-directed actions, which are governed by
action-outcome contingencies and sensitive to change in the
expected value of the outcome, to habits which are less
dependent on action-outcome relations and insensitive to
changes in outcome value. Previous studies in rats have
shown that interval schedules of reinforcement favor habit
formation while ratio schedules favor goal-directed
behavior. However, the molecular mechanisms underlying habit
formation are not well understood. Endocannabinoids, which
can function as retrograde messengers acting through
presynaptic CB1 receptors, are highly expressed in the
dorsolateral striatum, a key region involved in habit
formation. Using a reversible devaluation paradigm, we
confirmed that in mice random interval schedules also favor
habit formation compared with random ratio schedules. We
also found that training with interval schedules resulted in
a preference for exploration of a novel lever, whereas
training with ratio schedules resulted in less
generalization and more exploitation of the reinforced
lever. Furthermore, mice carrying either a heterozygous or a
homozygous null mutation of the cannabinoid receptor type I
(CB1) showed reduced habit formation and enhanced
exploitation. The impaired habit formation in CB1 mutant
mice cannot be attributed to chronic developmental or
behavioral abnormalities because pharmacological blockade of
CB1 receptors specifically during training also impairs
habit formation. Taken together our data suggest that
endocannabinoid signaling is critical for habit formation.
© 2007 Hilário, Clouse, Yin, Costa.},
Doi = {10.3389/neuro.07/006.2007},
Key = {fds254779}
}
@article{fds254793,
Author = {Yin, HH and Davis, MI and Ronesi, JA and Lovinger,
DM},
Title = {The role of protein synthesis in striatal long-term
depression.},
Journal = {The Journal of neuroscience : the official journal of the
Society for Neuroscience},
Volume = {26},
Number = {46},
Pages = {11811-11820},
Year = {2006},
Month = {November},
ISSN = {0270-6474},
url = {http://dx.doi.org/10.1523/jneurosci.3196-06.2006},
Abstract = {Long-term depression (LTD) at the corticostriatal synapse is
postsynaptically induced but presynaptically expressed, the
depression being a result of retrograde endocannabinoid
signaling that activates presynaptic cannabinoid CB1
receptors and reduces the probability of glutamate release.
To study the role of protein synthesis in striatal LTD, we
used a striatum-only preparation in which the presynaptic
cell body is cut off, leaving intact only its axons, whose
terminals synapse on medium spiny neurons. LTD (duration
>150 min) was induced in this preparation, thus providing
evidence that transcription in the presynaptic cell nucleus
is not necessary for this form of plasticity. The
maintenance of striatal LTD, however, was blocked by bath
application of protein translation inhibitors but not by the
same inhibitors loaded into the postsynaptic cell. These
results suggest that local translation is critical for the
expression of striatal LTD, distinguishing this form of
mammalian synaptic plasticity from other forms that require
postsynaptic protein synthesis. Possible roles of axonal or
glial translation in striatal LTD are considered.},
Doi = {10.1523/jneurosci.3196-06.2006},
Key = {fds254793}
}
@article{fds254792,
Author = {Dang, MT and Yokoi, F and Yin, HH and Lovinger, DM and Wang, Y and Li,
Y},
Title = {Disrupted motor learning and long-term synaptic plasticity
in mice lacking NMDAR1 in the striatum.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {103},
Number = {41},
Pages = {15254-15259},
Year = {2006},
Month = {October},
ISSN = {0027-8424},
url = {http://dx.doi.org/10.1073/pnas.0601758103},
Abstract = {Much research has implicated the striatum in motor learning,
but the underlying mechanisms have not been identified.
Although NMDA receptor (NMDAR)-dependent long-term
potentiation has been observed in the striatum, its
involvement in motor learning remains unclear. To examine
the role of striatal NMDAR in motor learning, we created
striatum-specific NMDAR1 subunit knockout mice, analyzed the
striatal anatomy and neuronal morphology of these mice,
evaluated their performance on well established motor tasks,
and performed electrophysiological recordings to assay
striatal NMDAR function and long-term synaptic plasticity.
Our results show that deleting the NMDAR1 subunit of the
NMDAR specifically in the striatum, which virtually
abolished NMDAR-mediated currents, resulted in only small
changes in striatal neuronal morphology but severely
impaired motor learning and disrupted dorsal striatal
long-term potentiation and ventral striatal long-term
depression.},
Doi = {10.1073/pnas.0601758103},
Key = {fds254792}
}
@article{fds254791,
Author = {Yin, HH and Knowlton, BJ},
Title = {The role of the basal ganglia in habit formation.},
Journal = {Nature reviews. Neuroscience},
Volume = {7},
Number = {6},
Pages = {464-476},
Year = {2006},
Month = {June},
ISSN = {1471-003X},
url = {http://dx.doi.org/10.1038/nrn1919},
Abstract = {Many organisms, especially humans, are characterized by
their capacity for intentional, goal-directed actions.
However, similar behaviours often proceed automatically, as
habitual responses to antecedent stimuli. How are
goal-directed actions transformed into habitual responses?
Recent work combining modern behavioural assays and
neurobiological analysis of the basal ganglia has begun to
yield insights into the neural basis of habit
formation.},
Doi = {10.1038/nrn1919},
Key = {fds254791}
}
@article{fds254788,
Author = {Yin, HH and Zhuang, X and Balleine, BW},
Title = {Instrumental learning in hyperdopaminergic
mice.},
Journal = {Neurobiology of learning and memory},
Volume = {85},
Number = {3},
Pages = {283-288},
Year = {2006},
Month = {May},
ISSN = {1074-7427},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16423542},
Abstract = {In two experiments we investigated the effects of elevated
dopaminergic tone on instrumental learning and performance
using dopamine transporter knockdown (DAT KD) mice. In
Experiment 1, we showed that both DAT KD mice and wild-type
controls were similarly sensitive to outcome devaluation
induced by sensory specific satiety, indicating normal
action-outcome learning in both groups. In Experiment 2, we
used a Pavlovian-to-instrumental transfer procedure to
assess the potentiation of instrumental responding by
Pavlovian conditional stimuli (CS). Although during the
Pavlovian training phase the DAT KD mice entered the food
magazine more frequently in the absence of the CS, when
tested later both groups showed outcome-selective PIT. These
results suggest that the elevated dopaminergic tone reduced
the selectivity of stimulus control over conditioned
behavior, but did not affect instrumental
learning.},
Doi = {10.1016/j.nlm.2005.12.001},
Key = {fds254788}
}
@article{fds254789,
Author = {Wang, Z and Kai, L and Day, M and Ronesi, J and Yin, HH and Ding, J and Tkatch, T and Lovinger, DM and Surmeier, DJ},
Title = {Dopaminergic control of corticostriatal long-term synaptic
depression in medium spiny neurons is mediated by
cholinergic interneurons.},
Journal = {Neuron},
Volume = {50},
Number = {3},
Pages = {443-452},
Year = {2006},
Month = {May},
ISSN = {0896-6273},
url = {http://dx.doi.org/10.1016/j.neuron.2006.04.010},
Abstract = {Long-term depression (LTD) of the synapse formed between
cortical pyramidal neurons and striatal medium spiny neurons
is central to many theories of motor plasticity and
associative learning. The induction of LTD at this synapse
is thought to depend upon D(2) dopamine receptors localized
in the postsynaptic membrane. If this were true, LTD should
be inducible in neurons from only one of the two projection
systems of the striatum. Using transgenic mice in which
neurons that contribute to these two systems are labeled, we
show that this is not the case. Rather, in both cell types,
the D(2) receptor dependence of LTD induction reflects the
need to lower M(1) muscarinic receptor activity-a goal
accomplished by D(2) receptors on cholinergic interneurons.
In addition to reconciling discordant tracts of the striatal
literature, these findings point to cholinergic interneurons
as key mediators of dopamine-dependent striatal plasticity
and learning.},
Doi = {10.1016/j.neuron.2006.04.010},
Key = {fds254789}
}
@article{fds254790,
Author = {Yin, HH and Lovinger, DM},
Title = {Frequency-specific and D2 receptor-mediated inhibition of
glutamate release by retrograde endocannabinoid
signaling.},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {103},
Number = {21},
Pages = {8251-8256},
Year = {2006},
Month = {May},
ISSN = {0027-8424},
url = {http://dx.doi.org/10.1073/pnas.0510797103},
Abstract = {The mechanisms underlying modulation of corticostriatal
synaptic transmission by D2-like receptors (D2Rs) have been
controversial. A recent study suggested that D2Rs inhibit
glutamate release at this synapse, but only during
high-frequency synaptic activation. Because the release of
postsynaptic endocannabinoids (eCBs), which act as
retrograde messengers to inhibit presynaptic glutamate
release, can be triggered by D2R activation and intense
synaptic activation, such a mechanism could mediate
dopaminergic modulation of corticostriatal transmission.
Here, we show that D2R activation reduces excitatory
transmission onto striatal medium spiny neurons at a
stimulation frequency of 20 Hz but not at 1 Hz. This form of
inhibition requires CB1 receptor activation, as evidenced by
the fact that it is blocked by AM251 [N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide],
a CB1 antagonist, and is absent in CB1 knockout mice. It is
also blocked by postsynaptic intracellular calcium
chelation, by group I metabotropic glutamate receptor
antagonism, and by inhibition of postsynaptic phospholipase
C. These results demonstrate a previously unrecognized role
for retrograde eCB signaling in reversible and
frequency-specific inhibition of glutamate release by the
activation of striatal D2Rs.},
Doi = {10.1073/pnas.0510797103},
Key = {fds254790}
}
@article{fds254756,
Author = {Yin, HH and Knowlton, BJ and Balleine, BW},
Title = {Inactivation of dorsolateral striatum enhances sensitivity
to changes in the action-outcome contingency in instrumental
conditioning.},
Journal = {Behavioural brain research},
Volume = {166},
Number = {2},
Pages = {189-196},
Year = {2006},
Month = {January},
ISSN = {0166-4328},
url = {http://dx.doi.org/10.1016/j.bbr.2005.07.012},
Abstract = {Actions become compulsive when they are no longer controlled
by their consequences. Compulsivity can be assessed using
the omission procedure in which animals are required to
withhold a previously reinforced action to earn reward. The
current study tested the hypothesis that inactivation of the
dorsolateral striatum (DLS), a structure implicated in
habitual behavior, can enhance sensitivity to changes in the
action-outcome contingency during omission training, thus
leading to a reduction in compulsive responding. Over 10
days rats were trained to press a freely available lever for
sucrose reward delivered on interval schedules of
reinforcement. After learning to press the lever at a stable
and high rate, rats in the omission group received a session
in which the rewards were now delayed by pressing the lever;
i.e. withholding lever pressing resulted in increased access
to reward. A control group was yoked to the omission group
and received the same number and pattern of reward delivery
but without the omission contingency. Half the rats in each
group received infusions of vehicle into the DLS prior to
this training whereas the remainder received an infusion of
the GABA-A receptor agonist muscimol. On the next day, the
effect of these treatments was assessed on a probe test in
which the tendency of the various groups to press the lever
was assessed in extinction and without drug infusion. Rats
that received vehicle infusions prior to the omission
session showed complete insensitivity to the newly imposed
omission contingency. In contrast, rats given the infusion
of muscimol selectively reduced lever pressing compared to
yoked controls. Thus, extended training with interval
schedules resulted in compulsive lever pressing that
prevented the learning of the omission contingency, whereas
inactivation of the DLS appeared to enhance the rats'
sensitivity to this change in the action-outcome
contingency.},
Doi = {10.1016/j.bbr.2005.07.012},
Key = {fds254756}
}
@article{fds254781,
Author = {Yin, HH and Knowlton, BJ and Balleine, BW},
Title = {Reversible inactivation of dorsolateral striatum enhances
sensitivity to changes in action-outcome contingency in
instrumental conditioning},
Journal = {Behavioural Brain Research},
Volume = {66},
Number = {2},
Pages = {189-196},
Year = {2006},
Key = {fds254781}
}
@article{fds254786,
Author = {Yin, HH and Ostlund, SB and Knowlton, BJ and Balleine,
BW},
Title = {The role of the dorsomedial striatum in instrumental
conditioning.},
Journal = {The European journal of neuroscience},
Volume = {22},
Number = {2},
Pages = {513-523},
Year = {2005},
Month = {July},
url = {http://dx.doi.org/10.1111/j.1460-9568.2005.04218.x},
Abstract = {Considerable evidence suggests that, in instrumental
conditioning, rats learn the relationship between actions
and their specific consequences or outcomes. The present
study examined the role of the dorsomedial striatum (DMS) in
this type of learning after excitotoxic lesions and
reversible, muscimol-induced inactivation. In three
experiments, rats were first trained to press two levers for
distinct outcomes, and then tested after training using a
variety of behavioural assays that have been established to
detect action-outcome learning. In Experiment 1,
pre-training lesions of the posterior DMS abolished the
sensitivity of rats' instrumental performance to both
outcome devaluation and contingency degradation when tested
in extinction, whereas lesions of the anterior DMS had no
effect. In Experiment 2, both pre-training and post-training
lesions of the posterior DMS were equally effective in
reducing the sensitivity of performance both to devaluation
and degradation treatments. In Experiment 3, the infusion of
muscimol into the posterior DMS selectively abolished
sensitivity of performance to devaluation and contingency
degradation without impairing the ability of rats to
discriminate either the instrumental actions performed or
the identity of the earned outcomes. Taken together, these
results suggest that the posterior region of the DMS is a
crucial neural substrate for the acquisition and expression
of action-outcome associations in instrumental
conditioning.},
Doi = {10.1111/j.1460-9568.2005.04218.x},
Key = {fds254786}
}
@article{fds254787,
Author = {Yin, HH and Knowlton, BJ and Balleine, BW},
Title = {Blockade of NMDA receptors in the dorsomedial striatum
prevents action-outcome learning in instrumental
conditioning.},
Journal = {The European journal of neuroscience},
Volume = {22},
Number = {2},
Pages = {505-512},
Year = {2005},
Month = {July},
url = {http://dx.doi.org/10.1111/j.1460-9568.2005.04219.x},
Abstract = {Although there is consensus that instrumental conditioning
depends on the encoding of action-outcome associations, it
is not known where this learning process is localized in the
brain. Recent research suggests that the posterior
dorsomedial striatum (pDMS) may be the critical locus of
these associations. We tested this hypothesis by examining
the contribution of N-methyl-D-aspartate receptors (NMDARs)
in the pDMS to action-outcome learning. Rats with bilateral
cannulae in the pDMS were first trained to perform two
actions (left and right lever presses), for sucrose
solution. After the pre-training phase, they were given an
infusion of the NMDA antagonist 2-amino-5-phosphonopentanoic
acid (APV, 1 mg/mL) or artificial cerebral spinal fluid
(ACSF) before a 30-min session in which pressing one lever
delivered food pellets and pressing the other delivered
fruit punch. Learning during this session was tested the
next day by sating the animals on either the pellets or
fruit punch before assessing their performance on the two
levers in extinction. The ACSF group selectively reduced
responding on the lever that, in training, had earned the
now devalued outcome, whereas the APV group did not.
Experiment 2 replicated the effect of APV during the
critical training session but found no effect of APV given
after acquisition and before test. Furthermore, Experiment 3
showed that the effect of APV on instrumental learning was
restricted to the pDMS; infusion into the dorsolateral
striatum did not prevent learning. These experiments provide
the first direct evidence that, in instrumental
conditioning, NMDARs in the dorsomedial striatum are
involved in encoding action-outcome associations.},
Doi = {10.1111/j.1460-9568.2005.04219.x},
Key = {fds254787}
}
@article{fds254785,
Author = {Yin, HH and Knowlton, BJ},
Title = {Contributions of striatal subregions to place and response
learning.},
Journal = {Learning & memory (Cold Spring Harbor, N.Y.)},
Volume = {11},
Number = {4},
Pages = {459-463},
Year = {2004},
Month = {July},
url = {http://dx.doi.org/10.1101/lm.81004},
Abstract = {The involvement of different subregions of the striatum in
place and response learning was examined using a T-maze.
Rats were given NMDA lesions of the dorsolateral striatum
(DLS), anterior dorsomedial striatum (ADMS), posterior
dorsomedial striatum (PDMS), or sham surgery. They were then
trained to retrieve food from the west arm of the maze,
starting from the south arm, by turning left at the choice
point. After 7 d of training, with four trials a day, a
probe test was given in which the starting arm is inserted
as the north arm, at the opposite side of the maze. A left
turn would indicate a "response" strategy; a right turn, a
"place" strategy. The rats were then trained for 7 more
days, followed by a second probe test. Unlike rats in the
other groups, most of the rats in the PDMS group turned
left, using the response strategy on both probe tests. These
results suggest that the PDMS plays a role in spatially
guided behavior.},
Doi = {10.1101/lm.81004},
Key = {fds254785}
}
@article{fds254755,
Author = {Yin, HH and Knowlton, BJ and Balleine, BW},
Title = {Lesions of dorsolateral striatum preserve outcome expectancy
but disrupt habit formation in instrumental
learning.},
Journal = {The European journal of neuroscience},
Volume = {19},
Number = {1},
Pages = {181-189},
Year = {2004},
Month = {January},
url = {http://dx.doi.org/10.1111/j.1460-9568.2004.03095.x},
Abstract = {Habits are controlled by antecedent stimuli rather than by
goal expectancy. Interval schedules of feedback have been
shown to generate habits, as revealed by the insensitivity
of behaviour acquired under this schedule to outcome
devaluation treatments. Two experiments were conducted to
assess the role of the dorsolateral striatum in habit
learning. In Experiment 1, sham operated controls and rats
with dorsolateral striatum lesions were trained to press a
lever for sucrose under interval schedules. After training,
the sucrose was devalued by inducing taste aversion to it
using lithium chloride, whereas saline injections were given
to the controls. Only rats given the devaluation treatment
reduced their consumption of sucrose and this reduction was
similar in both the sham and the lesioned groups. All rats
were then returned to the instrumental chamber for an
extinction test, in which the lever was extended but no
sucrose was delivered. In contrast to sham operated
controls, rats with dorsolateral striatum lesions refrained
from pressing the lever if the outcome was devalued. To
assess the specificity of the role of dorsolateral striatum
in this effect a second experiment was conducted in which a
group with lesions of dorsomedial striatum was added. In
relation now to both the sham and the dorsomedial lesioned
groups, only rats with lesions of dorsolateral striatum
significantly reduced responding after outcome devaluation.
In conclusion, this study provides direct evidence that the
dorsolateral striatum is necessary for habit formation.
Furthermore, it suggests that, when the habit system is
disrupted, control over instrumental performance reverts to
the system controlling the performance of goal-directed
instrumental actions.},
Doi = {10.1111/j.1460-9568.2004.03095.x},
Key = {fds254755}
}
@article{fds254784,
Author = {Yin, HH and Knowlton, BJ and Balleine, BW},
Title = {Lesions of the dorsolateral striatum abolish habits and
preserve goal expectancy},
Journal = {European Journal of Neuroscience},
Volume = {19},
Pages = {1-9},
Year = {2004},
Key = {fds254784}
}
@article{fds254783,
Author = {Yin, H and Bardgett, ME and Csernansky, JG},
Title = {Kainic acid lesions disrupt fear-mediated memory
processing.},
Journal = {Neurobiology of learning and memory},
Volume = {77},
Number = {3},
Pages = {389-401},
Year = {2002},
Month = {May},
ISSN = {1074-7427},
url = {http://dx.doi.org/10.1006/nlme.2001.4037},
Abstract = {Previous research has shown that hippocampal lesions impair
the expression of fear conditioning. This fear conditioning
deficit may be due to memory impairment or a reduction in
fear in lesioned animals. To address these possibilities,
the authors examined unconditioned and conditioned fear in
male Sprague-Dawley rats that had received
intracerebroventricular (ICV) infusions of kainic acid (KA)
30 days prior to testing. Animals that had received
bilateral ICV infusions of KA (1.0 microl of 0.8 mg/ml
solution per side) exhibited cell loss that was primarily
confined to the CA3 region of the dorsal hippocampus. Kainic
acid lesions impaired contextual and cued fear conditioning
but did not affect unconditioned fear in a light:dark test
of anxiety. Moreover, animals with KA lesions did not
habituate to the light:dark apparatus when tested over a
3-day period. These data suggest that decreases in fear
conditioning produced by hippocampal lesions reflect a
memory deficit and not a lack of fear.},
Doi = {10.1006/nlme.2001.4037},
Key = {fds254783}
}
@article{fds254780,
Author = {Yin, HH and Knowlton, BJ},
Title = {Reinforcer devaluation abolishes conditioned cue preference:
evidence for stimulus-stimulus associations.},
Journal = {Behavioral neuroscience},
Volume = {116},
Number = {1},
Pages = {174-177},
Year = {2002},
Month = {February},
ISSN = {0735-7044},
url = {http://dx.doi.org/10.1037//0735-7044.116.1.174},
Abstract = {In the conditioned cue preference (CCP) task, the subject is
presented with a cue paired with food reward, resulting in a
preference for the paired cue when allowed to choose later.
To clarify the learning involved, the authors devalued the
reinforcer after training by inducing a taste aversion to
the food. In five 30-min sessions, rats were confined in 1
arm of a radial arm maze and presented with food. These
reinforced sessions alternated with 5 unreinforced sessions
in a nonadjacent arm. Devaluation was then accomplished in 1
group by inducing taste aversion; controls received either
saline or unpaired lithium chloride treatment. When tested
later, both the saline group and the unpaired group
preferred the previously reinforced arm, but the devalued
group showed aversion to it. Thus, CCP is mediated by the
stimulus-reinforcer association; when the reinforcer is
devalued, the preference is also abolished.},
Doi = {10.1037//0735-7044.116.1.174},
Key = {fds254780}
}
@article{fds336565,
Author = {Kwong-yin Fock and H},
Title = {Retail outlet location decision maker – franchisor or
franchisee?},
Journal = {Marketing Intelligence & Planning},
Volume = {19},
Number = {3},
Pages = {171-179},
Publisher = {Emerald},
Year = {2001},
Month = {June},
url = {http://dx.doi.org/10.1108/02634500110391717},
Abstract = {This study focuses on a unique retail outlet location
decision-making problem found in business format franchising
industries. The problem is derived from the latent conflict
in the relationship between franchisor and franchisees. An
empirical study was carried out to compare benefits of two
different outlet allocation decision modes: centralised
planning mode (locations allocated by the franchisor) and
decentralised planning mode (franchisees given autonomy to
select the location of their own outlets). Research findings
revealed that the decentralised location decision mode is
more beneficial to the franchise system with a lower level
of customer loyalty. © 2001, MCB UP Limited},
Doi = {10.1108/02634500110391717},
Key = {fds336565}
}
%% Books
@book{fds373559,
Author = {Yin, HH},
Title = {The integrative functions of the basal ganglia},
Pages = {1-319},
Year = {2023},
Month = {November},
ISBN = {9781498768696},
url = {http://dx.doi.org/10.1201/9780429154461},
Abstract = {This volume is the first comprehensive and single-authored
book on the functions of the basal ganglia. The goal is to
provide a new synthesis of diverse areas of research on the
basal ganglia, from cellular mechanisms of synaptic
transmission and plasticity to neural circuit mechanisms
underlying behavior. A global theory of basal ganglia
function incorporating research from the last 40 years is
presented. I hope to explain for the first time how the
basal ganglia generate behavior, how they contribute to
learning and memory, and how impairments in basal ganglia
function can lead to neurological and psychiatric disorders.
Features: • The only single-authored book on the basal
ganglia with coverage of the latest literature • Spans
multiple levels of analysis, from cellular physiology to
behavior • Includes coverage of clinical symptoms,
encompassing neuropsychology, movement disorders, and
psychiatric disorders • Discusses the role of the basal
ganglia in learning and memory.},
Doi = {10.1201/9780429154461},
Key = {fds373559}
}
%% Chapters in Books
@misc{fds368072,
Author = {Yin, H},
Title = {The crisis in neuroscience},
Pages = {23-48},
Booktitle = {The Interdisciplinary Handbook of Perceptual Control Theory:
Living Control Systems IV},
Year = {2020},
Month = {January},
ISBN = {9780128189498},
url = {http://dx.doi.org/10.1016/B978-0-12-818948-1.00003-4},
Abstract = {The dominant paradigm in neuroscience, the linear causation
paradigm, has led to a number of conceptual confusions about
how the brain generates behavior. Because biological
organisms are collections of closed loop control systems,
their behaviors cannot be explained by a sequence of causes
and effects. On account of simultaneous actions of forward
and feedback paths in the closed loop, a major emergent
property of control systems is circular causation. Methods
used to analyze input-output systems are not only inadequate
for understanding circular causation; they can produce
misleading results. I shall use specific examples from the
history of neuroscience to illustrate the fallacy of the
conventional input/output analysis of behavior. I shall also
discuss why a seemingly simple mechanism like negative
feedback control can have complex and counterintuitive
properties, and why generations of students, influenced by
modern engineering conventions and the cybernetic tradition,
have misunderstood the central features of control
theory.},
Doi = {10.1016/B978-0-12-818948-1.00003-4},
Key = {fds368072}
}
@misc{fds254737,
Author = {Yin, HH},
Title = {Restoring purpose in behavior},
Volume = {9783642398759},
Pages = {319-347},
Booktitle = {Computational and Robotic Models of the Hierarchical
Organization of Behavior},
Publisher = {Springer Berlin Heidelberg},
Editor = {Baldassare G},
Year = {2013},
Month = {January},
ISBN = {9783642398742},
url = {http://dx.doi.org/10.1007/978-3-642-39875-9_14},
Abstract = {The dominant paradigm in the study of behavior today is the
linear causation paradigm. This paradigm, inspired by
classical physics, assumes that causes precede effects, that
the behavior of organisms is caused by antecedent events
inside and outside the organism, and that future states such
as goals and purposes cannot possibly cause behavior. It is
the basis of the general linear model in psychology and the
input/output analysis in neuroscience. But linear causation
does not apply to any control system with negative feedback.
Here I shall argue that organisms are collections of such
negative feedback systems that control their perceptual
inputs. The chief difference between the behavior of living
organisms and that of non-living things is the presence of
control. Rather than the effect of some prior cause,
behavior is the observable manifestation of control in
teleological systems that act on the environment to make
inputs match their internal reference values. The previous
rejection of control theory in the behavioral sciences was
largely based on a misunderstanding of the principles of
negative feedback control. I discuss the types of behavioral
control enabled by the hierarchical organization and the
experimental method for testing the controlled
variable.},
Doi = {10.1007/978-3-642-39875-9_14},
Key = {fds254737}
}
@misc{fds197634,
Author = {Rossi MA and Yin HH},
Title = {The role of the dorsal striatum in instrumental
learning},
Volume = {2},
Booktitle = {Animal models of movement disorders},
Publisher = {Humana Press},
Year = {2011},
Key = {fds197634}
}
@misc{fds211329,
Author = {H. Yin and Costa RM},
Title = {Dopamine and glutamate interactions in the
striatum},
Booktitle = {Dopamine-glutamate interactions in the basal
ganglia},
Year = {2011},
Key = {fds211329}
}
@misc{fds330364,
Author = {Yin, HH and Knowlton, BJ},
Title = {Addiction and learning in the brain},
Pages = {167-184},
Booktitle = {Handbook of Implicit Cognition and Addiction},
Publisher = {SAGE PUBLICATIONS INC},
Year = {2005},
Month = {January},
ISBN = {9781412909747},
url = {http://dx.doi.org/10.4135/9781412976237.n12},
Abstract = {Addiction can be viewed as a maladaptive form of learning.
This chapter discusses the relevant types of learning
implicated in addiction and their neural substrates. First,
we describe the associative structures of various learning
processes-abstract descriptions of the content of learning
based on behavioral studies. We then attempt to link various
types of adaptive behavior and their modification by
distinct learning processes to specific neural substrates.
In particular, we argue that parallel but interacting
cortico-basal ganglia networks in the cerebrum provide the
neural implementations of associative structures from
learning theory, and that abnormal interactions between
these networks could result in addictive behavior. Finally,
we discuss the implications of such a conceptual framework
for our understanding of addiction. © 2006 by Sage
Publications, Inc.},
Doi = {10.4135/9781412976237.n12},
Key = {fds330364}
}
@misc{fds70708,
Author = {Yin, H. H. and Knowlton, B. J},
Title = {Addiction and learning},
Booktitle = {The Handbook of implicit cognition and addiction},
Publisher = {Thousand Oaks, CA: Sage Publications},
Editor = {R.W. Wiers and A.W. Stacy},
Year = {2005},
Key = {fds70708}
}
@misc{fds323504,
Author = {Yin, HH and Knowlton, BJ and Balleine, BW},
Title = {From habits to actions: Dorsolateral striatum lesions alter
the content of learning},
Journal = {ICONIP 2002 - Proceedings of the 9th International
Conference on Neural Information Processing: Computational
Intelligence for the E-Age},
Volume = {3},
Pages = {1579-1581},
Publisher = {Nanyang Technol. Univ},
Year = {2002},
Month = {January},
ISBN = {9789810475246},
url = {http://dx.doi.org/10.1109/ICONIP.2002.1202887},
Abstract = {Actions are controlled by the expectation of an outcome,
whereas habits are elicited by the prevailing stimuli,
autonomous of the outcome. In this study, the dorsolateral
striatum is shown to be necessary for the formation of a
habit. Rats were trained to press a lever under interval
schedules, which generated habitual responses in sham
operated controls. These rats showed similar response rates
whether or not the outcome had been independently made
aversive to them In contrast, although rats with
dorsolateral striatal lesions acquired the instrumental
response, they refrained from responding almost completely
after the goal had been devalued. Thus, damage to the
dorsolateral striatum prevented habit formation, resulting
in goal-directed behavior under conditions which generated
habits in normal animals.},
Doi = {10.1109/ICONIP.2002.1202887},
Key = {fds323504}
}
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