Upregulated inwardly rectifying K+current-mediated hypoactivity of parvalbumin interneurons underlies autism-like deficits in Bod1-deficient mice
Chen Li1
Kerui Wang1
Xingfeng Mao2
Takuya Sasaki3
Xiuxiu Liu4
Yingmei Lu1
1.Key Laboratory of Modern Toxicology of Ministry of Education;School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China3.Department of Pharmacology,Graduate School of Pharmaceutical Sciences,Tohoku University,Sendai 980-8578,Japan4.Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases,Ministry of Education;International Joint Laboratory for Drug Target of Critical Illnesses;Key Laboratory of Cardiovascular &Cerebrovascular Medicine;School of Pharmacy,Nanjing Medical University,Nanjing,Jiangsu 211166,China
摘要：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.
机标关键词：parvalbumincurrentmiceautism-likebod1-deficientdeficitshypoactivityinterneurons
分类号：R749.94(精神病学)
论文发表日期：2025-07-30
在线出版日期：2025-10-11（本平台首次上网日期，不代表文献的发表时间）
页数：13( 417-429 )
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