Dysregulation of the Synaptic Cytoskeleton in the PFC Drives Neural Circuit Pathology, Leading to Social Dysfunction.
Arp2/3
ArpC3
basolateral amygdala
circuit pathology
cytoskeleton
neural circuit
prefrontal cortex
schizophrenia
social behavior
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
28 07 2020
28 07 2020
Historique:
received:
18
02
2020
revised:
15
05
2020
accepted:
07
07
2020
entrez:
30
7
2020
pubmed:
30
7
2020
medline:
11
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32726629
pii: S2211-1247(20)30946-3
doi: 10.1016/j.celrep.2020.107965
pmc: PMC8000056
mid: NIHMS1617641
pii:
doi:
Substances chimiques
Actin-Related Protein 2-3 Complex
0
Arpc3 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107965Subventions
Organisme : NINDS NIH HHS
ID : R01 NS059957
Pays : United States
Organisme : NINDS NIH HHS
ID : R56 NS059957
Pays : United States
Organisme : NIMH NIH HHS
ID : R56 MH117429
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH117429
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH112883
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH103374
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007171
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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