Upregulated inwardly rectifying K current-mediated hypoactivity of parvalbumin interneurons underlies autism-like deficits in -deficient mice.

Parvalbumin-positive (PV ) interneuron dysfunction is believed to be linked to autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors. However, the mechanisms behind PV interneuron dysfunction remain largely unclear. Here, we found that a deficiency of Biorientation Defective 1 ( ) in PV interneurons led to an ASD-like phenotype in ; mice. Mechanistically, we observed that deficiency induced hypoactivity of PV interneurons and hyperactivity of calcium/calmodulin-dependent protein kinase Ⅱ alpha (CaMKⅡα) neurons in the medial prefrontal cortex, as determined by whole-cell patch-clamp recording. Additionally, deficiency decreased the power of high-gamma oscillation, assessed by multi-channel electrophysiological recording. Furthermore, we found that deficiency enhanced the inwardly rectifying K current, leading to an increase in the resting membrane potential of PV interneurons. Importantly, the gain-of-function of improved social deficits and stereotypical behaviors in ; mice. These findings provide mechanistic insights into the PV interneuron dysfunction and suggest new strategies for developing PV interneuron-targeted therapies for ASD.