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 g-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.