Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction.

Il Hwan Kim, Namsoo Kim, Sunwhi Kim, Koji Toda, Christina M Catavero, Jamie L Courtland, Henry H Yin, Scott H Soderling

Cell reports 2020 Jul 28

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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. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Il Hwan Kim, Namsoo Kim, Sunwhi Kim, Koji Toda, Christina M Catavero, Jamie L Courtland, Henry H Yin, Scott H Soderling. Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction. Cell reports. 2020 Jul 28;32(4):107965