FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes

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<jats:title>Abstract</jats:title><jats:p>Abnormalities in GABAergic inhibitory circuits have been implicated in the aetiology of autism spectrum disorder (ASD). ASD is caused by genetic and environmental factors. Several genes have been associated with syndromic forms of ASD, including <jats:italic>FOXG1</jats:italic>. However, when and how dysregulation of <jats:italic>FOXG1</jats:italic> can result in defects in inhibitory circuit development and ASD-like social impairments is unclear. Here, we show that increased or decreased <jats:italic>FoxG1</jats:italic> expression in both excitatory and inhibitory neurons results in ASD-related circuit and social behavior deficits in our mouse models. We observe that the second postnatal week is the critical period when regulation of <jats:italic>FoxG1</jats:italic> expression is required to prevent subsequent ASD-like social impairments. Transplantation of GABAergic precursor cells prior to this critical period and reduction in GABAergic tone via <jats:italic>Gad2</jats:italic> mutation ameliorates and exacerbates circuit functionality and social behavioral defects, respectively. Our results provide mechanistic insight into the developmental timing of inhibitory circuit formation underlying ASD-like phenotypes in mouse models.</jats:p>

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