Publications [#333937] of Namsoo Kim

Journal Articles

1. Kim, IH; Rossi, MA; Aryal, DK; Racz, B; Kim, N; Uezu, A; Wang, F; Wetsel, WC; Weinberg, RJ; Yin, H; Soderling, SH (2015). Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine.. Nat Neurosci, 18(6), 883-891. [doi]
   (last updated on 2023/08/08)

   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.