{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:26:15Z","timestamp":1790857575861,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Autism spectrum disorder (ASD) is a group of diseases often characterized by poor sociability and challenges in social communication. The anterior cingulate cortex (ACC) is a core brain region for social function. Whether it contributes to the defects of social communication in ASD and whether it could be physiologically modulated to improve social communication have been poorly investigated. This study is aimed at addressing these questions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fragile X mental retardation 1 (FMR1) mutant and valproic acid (VPA)-induced ASD mice were used. Male\u2013female social interaction was adopted to elicit ultrasonic vocalization (USV). Immunohistochemistry was used to evaluate USV-activated neurons. Optogenetic and precise target transcranial magnetic stimulation (TMS) were utilized to modulate anterior cingulate cortex (ACC) neuronal activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In wild-type (WT) mice, USV elicited rapid expression of c-Fos in the excitatory neurons of the left but not the right ACC. Optogenetic inhibition of the left ACC neurons in WT mice effectively suppressed social-induced USV. In <jats:italic>FMR1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>- and VPA-induced ASD mice, significantly fewer c-Fos\/CaMKII-positive neurons were observed in the left ACC following USV compared to the control. Optogenetic activation of the left ACC neurons in <jats:italic>FMR1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> or VPA-pretreated mice significantly increased social activity elicited by USV. Furthermore, precisely stimulating neuronal activity in the left ACC, but not the right ACC, by repeated TMS effectively rescued the USV emission in these ASD mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The excitatory neurons in the left ACC are responsive to socially elicited USV. Their silence mediates the deficiency of social communication in <jats:italic>FMR1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> and VPA-induced ASD mice. Precisely modulating the left ACC neuronal activity by repeated TMS can promote the social communication in <jats:italic>FMR1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> and VPA-pretreated mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnbeh.2024.1387447","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T05:10:23Z","timestamp":1715749823000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Involvement and regulation of the left anterior cingulate cortex in the ultrasonic communication deficits of autistic mice"],"prefix":"10.3389","volume":"18","author":[{"given":"Yilin","family":"Hou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingding","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2019an","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Xian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.bandl.2012.10.002","article-title":"Mouse vocal communication system: are ultrasounds learned or innate?","volume":"124","author":"Arriaga","year":"2013","journal-title":"Brain Lang."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1264669","DOI":"10.3389\/fpsyt.2023.1264669","article-title":"Editorial: case reports in neuroimaging and stimulation","volume":"14","author":"Battaglia","year":"2023","journal-title":"Front. Psych."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"111161","DOI":"10.1016\/j.celrep.2022.111161","article-title":"Prenatal environmental stressors impair postnatal microglia function and adult behavior in males","volume":"40","author":"Block","year":"2022","journal-title":"Cell Rep."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/cns.13769","article-title":"Brain stimulation: a therapeutic approach for the treatment of neurological disorders","volume":"28","author":"Camacho-Conde","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"76","DOI":"10.3389\/fnbeh.2015.00076","article-title":"Male mice song syntax depends on social contexts and influences female preferences","volume":"9","author":"Chabout","year":"2015","journal-title":"Front. Behav. Neurosci."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s41586-021-03403-8","article-title":"Flexible scaling and persistence of social vocal communication","volume":"593","author":"Chen","year":"2021","journal-title":"Nature"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e1001767","DOI":"10.1371\/journal.pbio.1001767","article-title":"Left brain, right brain: facts and fantasies","volume":"12","author":"Corballis","year":"2014","journal-title":"PLoS Biol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1007\/s12264-022-00904-y","article-title":"Shanghai autism early development: an integrative Chinese ASD cohort","volume":"38","author":"Dai","year":"2022","journal-title":"Neurosci. Bull."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"787448","DOI":"10.3389\/fnsys.2022.787448","article-title":"Lateralized changes in language associated auditory and somatosensory cortices in autism","volume":"16","author":"Deemyad","year":"2022","journal-title":"Front. Syst. Neurosci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/325249a0","article-title":"Left hemisphere advantage in the mouse brain for recognizing ultrasonic communication calls","volume":"325","author":"Ehret","year":"1987","journal-title":"Nature"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1177\/1073858414550658","article-title":"Synaptic plasticity and memory: new insights from hippocampal left-right asymmetries","volume":"21","author":"El-Gaby","year":"2015","journal-title":"Neuroscientist"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"eade6992","DOI":"10.1126\/sciadv.ade6992","article-title":"Cortical circuits modulate mouse social vocalizations","volume":"9","author":"Gan-Or","year":"2023","journal-title":"Sci. Adv."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s12264-019-00365-w","article-title":"Medial preoptic area modulates courtship ultrasonic vocalization in adult male mice","volume":"35","author":"Gao","year":"2019","journal-title":"Neurosci. Bull."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1038\/s41593-019-0445-9","article-title":"Anterior cingulate cortex dysfunction underlies social deficits in shank 3 mutant mice","volume":"22","author":"Guo","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.bbr.2016.05.042","article-title":"Non-parametric analysis of neurochemical effects and arc expression in amphetamine-induced 50-kHz ultrasonic vocalization","volume":"312","author":"Hamed","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.bbr.2017.05.052","article-title":"Spectral and temporal properties of calls reveal deficits in ultrasonic vocalizations of adult Fmr 1 knockout mice","volume":"332","author":"Hodges","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.bbrc.2021.02.086","article-title":"LF-rTMS ameliorates social dysfunction of FMR1(\u2212\/\u2212) mice via modulating Akt\/GSK-3beta signaling","volume":"550","author":"Hou","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.neuropsychologia.2017.06.008","article-title":"Neural networks underlying language and social cognition during self-other processing in autism spectrum disorders","volume":"102","author":"Kana","year":"2017","journal-title":"Neuropsychologia"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nrn.2017.15","article-title":"Integration of optogenetics with complementary methodologies in systems neuroscience","volume":"18","author":"Kim","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/j.1601-183X.2010.00603.x","article-title":"Translating mouse vocalizations: prosody and frequency modulation","volume":"10","author":"Lahvis","year":"2011","journal-title":"Genes Brain Behav."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/S0140-6736(18)31129-2","article-title":"Autism spectrum disorder","volume":"392","author":"Lord","year":"2018","journal-title":"Lancet"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/jcpp.13497","article-title":"Perceived child impairment and the 'autism epidemic'","volume":"63","author":"Lundstrom","year":"2022","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.brs.2016.03.010","article-title":"The clinical TMS Society consensus review and treatment recommendations for TMS therapy for major depressive disorder","volume":"9","author":"Perera","year":"2016","journal-title":"Brain Stimul."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/7854_2015_433","article-title":"Treatment approaches in rodent models for autism Spectrum disorder","volume":"30","author":"Pietropaolo","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1007\/s10803-020-04853-1","article-title":"Structural and pragmatic language impairments in children evaluated for autism Spectrum disorder (ASD)","volume":"53","author":"Reindal","year":"2023","journal-title":"J. Autism Dev. Disord."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.1007\/s00429-019-01945-2","article-title":"The cingulate cortex and limbic systems for emotion, action, and memory","volume":"224","author":"Rolls","year":"2019","journal-title":"Brain Struct. Funct."},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-030-21293-3_1","article-title":"SimNIBS 2.1: a comprehensive pipeline for individualized electric field modelling for transcranial brain stimulation","volume-title":"Brain and human body modeling: Computational human modeling at EMBC 2018","author":"Saturnino","year":"2019"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"5326","DOI":"10.1109\/EMBC44109.2020.9175802","article-title":"Accurate TMS head modeling: interfacing SimNIBS and BEM-FMM in a MATLAB-based module","volume":"2020","author":"Saturnino","year":"2020","journal-title":"Annu. Int. Conf. IEEE Eng. Med. Biol. Soc."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"3724","DOI":"10.1016\/j.cub.2020.07.039","article-title":"Anterior cingulate cortex signals attention in a social paradigm that manipulates reward and shock","volume":"30","author":"Schneider","year":"2020","journal-title":"Curr. Biol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/7854_2015_407","article-title":"Genetic animal models for autism Spectrum disorder","volume":"30","author":"Schroeder","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1002\/aur.2268","article-title":"Identifying language and cognitive profiles in children with ASD via a cluster analysis exploration: implications for the new ICD-11","volume":"13","author":"Silleresi","year":"2020","journal-title":"Autism Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.brs.2022.01.009","article-title":"TMS with fast and accurate electronic control: measuring the orientation sensitivity of corticomotor pathways","volume":"15","author":"Souza","year":"2022","journal-title":"Brain Stimul."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1002\/aur.1564","article-title":"Early communication deficits in the shank 1 knockout mouse model for autism spectrum disorder: developmental aspects and effects of social context","volume":"9","author":"Sungur","year":"2016","journal-title":"Autism Res."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neubiorev.2019.04.012","article-title":"Behavioral neuroscience of autism","volume":"110","author":"Takumi","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3389\/fncel.2018.00046","article-title":"Low-frequency rTMS ameliorates autistic-like behaviors in rats induced by neonatal isolation through regulating the synaptic GABA transmission","volume":"12","author":"Tan","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1038\/s41467-018-03183-2","article-title":"Genetic tagging of active neurons in auditory cortex reveals maternal plasticity of coding ultrasonic vocalizations","volume":"9","author":"Tasaka","year":"2018","journal-title":"Nat. Commun."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cell.2014.08.037","article-title":"Behavioral variability through stochastic choice and its gating by anterior cingulate cortex","volume":"159","author":"Tervo","year":"2014","journal-title":"Cell"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.neuron.2019.05.025","article-title":"A specialized neural circuit gates social vocalizations in the mouse","volume":"103","author":"Tschida","year":"2019","journal-title":"Neuron"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"135985","DOI":"10.1016\/j.neulet.2021.135985","article-title":"Oxytocin administration modulates the complex type of ultrasonic vocalisation of mice pups prenatally exposed to valproic acid","volume":"758","author":"Tsuji","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e97244","DOI":"10.1371\/journal.pone.0097244","article-title":"A role for ultrasonic vocalisation in social communication and divergence of natural populations of the house mouse (Mus musculus domesticus)","volume":"9","author":"Von Merten","year":"2014","journal-title":"PLoS One"}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2024.1387447\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T05:10:25Z","timestamp":1715749825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2024.1387447\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":40,"alternative-id":["10.3389\/fnbeh.2024.1387447"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2024.1387447","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"article-number":"1387447"}}