Sensory integration in mouse insular cortex reflects GABA circuit maturation

Neuron. 2014 Aug 20;83(4):894-905. doi: 10.1016/j.neuron.2014.06.033. Epub 2014 Jul 31.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / genetics
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / physiology*
  • Diazepam / pharmacology
  • Disease Models, Animal
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / physiology*
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / physiology
  • Male
  • Methyl-CpG-Binding Protein 2 / genetics
  • Methyl-CpG-Binding Protein 2 / physiology
  • Mice
  • Mice, Knockout
  • Microfilament Proteins
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / growth & development*
  • Neural Pathways / physiology
  • Sensation / drug effects
  • Sensation / genetics
  • Sensation / physiology*
  • Species Specificity


  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Shank3 protein, mouse
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2
  • Diazepam