Upregulated inwardly rectifying K+current-mediated hypoactivity of parvalbumin interneurons underlies autism-like deficits in Bod1-deficient mice
Chen Li
Kerui Wang
Xingfeng Mao
Takuya Sasaki
Xiuxiu Liu
Yingmei Lu
Abstract：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 (Bod1) in PV+ interneurons led to an ASD-like phenotype in Pvalb-Cre; Bod1f/f mice. Mechanistically, we observed that Bod1 deficiency induced hypoactivity of PV+ interneurons and hyperactivity of calcium/calmodulin-dependent protein kinase II alpha (CaMK II α) neurons in the medial prefrontal cortex, as determined by whole-cell patch-clamp recording. Additionally, Bod1 deficiency decreased the power of high-gamma oscillation, assessed by in vivo multi-channel electrophysiological recording. Furthermore, we found that Bod1 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 Bod1 improved social deficits and stereotypical behaviors in Pvalb-Cre; Bod1f/f mice. These findings provide mechanistic insights into the PV+ interneuron dysfunction and suggest new strategies for developing PV+ interneuron-targeted therapies for ASD.
Keywords：parvalbumin neuronbiorientation defective 1inwardly rectifying K+currentautism spectrum disorder
Publication Date：2025-07-30
Online Publishing Date：2025-10-11(First online date of this platform, not the publication date of the document)
Pages：13( 417-429 )