Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsy-chiatric disorders.However,the molecular and circuit mechanisms underlying the dysregulation remain elusive.Here,by using a mouse model of chronic social defeat stress (CSDS),we observed that the dys-regulation varied drastically across individual projection neurons (PNs) in the basolateral amygdala(BLA),one of the kernel amygdala subregions critical for stress coping.While persistently reducing the extrasynaptic GABAA receptor (GABAAR)-mediated tonic current in the BLA PNs projecting to the ventral hippocampus (BLA → vHPC PNs),CSDS increased the current in those projecting to the anterodorsal bed nucleus of stria terminalis (BLA → adBNST PNs),suggesting projection-based dysregulation of tonic inhi-bition in BLA PNs by CSDS.Transcriptional and electrophysiological analysis revealed that the opposite CSDS influences were mediated by loss-and gain-of-function of δ-containing GABAARs (GABAA(δ)Rs) in BLA → vHPC and BLA → adBNST PNs,respectively.Importantly,it was the lost inhibition in the former population but not the augmentation in the latter population that correlated with the increased anxiety-like behavior in CSDS mice.Virally mediated maintenance of GABAA(δ)R currents in BLA → vHPC PNs occluded CSDS-induced anxiety-like behavior.These findings clarify the molecular sub-strate for the dysregulated GABAergic inhibition in amygdala circuits for stress-associated psychopathology.

Laboratory of Fear and Anxiety Disorders,Institute of Life Science,Nanchang University,Nanchang 330031,China;Jiangsu Provincial Key Laboratory of Anesthesiology,Xuzhou Medical University,Xuzhou 221004,China;Department of Biological Science,School of Life Science,Nanchang University,Nanchang 330031,China;Department of Ophthalmology,The Second Affiliated Hospital,Medical School of Nanchang University,Nanchang 330031,China

[1]Xia Qin;Han-Qing Pan;Shou-He Huang;Jia-Xin Zou;Zhi-Heng Zheng;Xiao-Xuan Liu;Wen-Jie You;Zhi-Peng Liu;Jun-Li Cao;Wen-Hua Zhang;Bing-Xing Pan-.GABAA(δ) receptor hypofunction in the amygdala-hippocampal circuit underlies stress-induced anxiety)[J].科学通报（英文版）,2022(01):97-110

neuropsy,chiatric,extrasynaptic,anterodorsal,adBNST,Virally,psychopathology

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