Neural circuit pathology driven by Shank3 mutation disrupts social behaviors

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dc.contributor.authorKim, Sunwhien
dc.contributor.authorKim, Yong-Eunen
dc.contributor.authorSong, Inuken
dc.contributor.authorUjihara, Yusukeen
dc.contributor.authorKim, Namsooen
dc.contributor.authorJiang, Yong-Huien
dc.contributor.authorYin, Henry H.en
dc.contributor.authorLee, Tae-Hoen
dc.contributor.authorKim, Il Hwanen
dc.date.accessioned2022-12-13T13:27:42Zen
dc.date.available2022-12-13T13:27:42Zen
dc.date.issued2022-06-07en
dc.date.updated2022-12-13T03:09:42Zen
dc.description.abstractDysfunctional 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.en
dc.description.notesSource info: CP-COMMUNITY-D-21-00183en
dc.description.versionAccepted versionen
dc.format.mimetypeapplication/pdfen
dc.identifier110906 (Article number)en
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2022.110906en
dc.identifier.eissn2211-1247en
dc.identifier.issn2211-1247en
dc.identifier.issue10en
dc.identifier.orcidLee, Tae-Ho [0000-0001-6458-0620]en
dc.identifier.otherS2211-1247(22)00681-7 (PII)en
dc.identifier.pmid35675770en
dc.identifier.urihttp://hdl.handle.net/10919/112863en
dc.identifier.volume39en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35675770en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectNeuroscienceen
dc.subjectShank3en
dc.subjectAmygdalaen
dc.subjectAutism spectrum disorderen
dc.subjectHuman fMRIen
dc.subjectin vivo Ca(2+) imagingen
dc.subjectNeural circuiten
dc.subjectOptogeneticsen
dc.subjectPrefrontal cortexen
dc.subjectRound social arenaen
dc.subjectSocial behavioren
dc.subjectBrain disordersen
dc.subjectIntellectual and Developmental Disabilities (IDD)en
dc.subjectMental Healthen
dc.subjectAutismen
dc.subjectPediatricen
dc.subjectNeurosciencesen
dc.subjectPediatric Research Initiativeen
dc.subjectBehavioral and Social Scienceen
dc.subjectNeurologicalen
dc.subject.meshPrefrontal Cortexen
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshDisease Models, Animalen
dc.subject.meshMicrofilament Proteinsen
dc.subject.meshNerve Tissue Proteinsen
dc.subject.meshSocial Behavioren
dc.subject.meshMutationen
dc.subject.meshOptogeneticsen
dc.subject.meshAutism Spectrum Disorderen
dc.titleNeural circuit pathology driven by Shank3 mutation disrupts social behaviorsen
dc.title.serialCell Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2022-05-10en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Psychologyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen

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