title: Sensory integration in mouse insular cortex reflects GABA circuit maturation.
abstract: Insular cortex (IC) contributes to a variety of complex brain functions, such as communication, social behavior, and self-awareness through the integration of sensory, emotional, and cognitive content. How the IC acquires its integrative properties remains unexplored. We compared the emergence of multisensory integration (MSI) in the IC of behaviorally distinct mouse strains. While adult C57BL/6 mice exhibited robust MSI, this capacity was impaired in the inbred BTBR T+tf/J mouse model of idiopathic autism. The deficit reflected weakened γ-aminobutyric acid (GABA) circuits and compromised postnatal pruning of cross-modal input. Transient pharmacological enhancement by diazepam in BTBR mice during an early sensitive period rescued inhibition and integration in the adult IC. Moreover, impaired MSI was common across three other monogenic models (GAD65, Shank3, and Mecp2 knockout mice) displaying behavioral phenotypes and parvalbumin-circuit abnormalities. Our findings offer developmental insight into a key neural circuit relevant to neuropsychiatric conditions like schizophrenia and autism.
authors.affiliation: Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gogolla
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Canadian Institute for Advanced Research, 180 Dundas Street West, Toronto ON M5G 1Z8, Canada.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Takesian
authors.affiliation: Department of Brain and Cognitive Sciences, McGovern Institute for Brain Research, MIT, 43 Vassar Street, Cambridge, MA 02139, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Fagiolini
authors.affiliation: Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA; Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Canadian Institute for Advanced Research, 180 Dundas Street West, Toronto ON M5G 1Z8, Canada. Electronic address: hensch@mcb.harvard.edu.
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000502:physiology; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D012677:Sensation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C492356:Shank3 protein, mouse; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D003975:Diazepam
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