Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment

作     者：Ziwei Shang Junhao Huang Nan Liu Xiaohui Zhang 

作者机构：State Key Laboratory of Cognitive Neuroscience and LearningIDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2023年第39卷第1期

页      面：1-13页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(32130043 and 32071025) the Interdisciplinary Research Fund of Beijing Normal University,China. 

主　　题：GABAergic inputs Axon initial segment Synaptic integration Axo-axonic cell Chandelier cell NEURON simulation Dynamic clamp 

摘      要：Differing from other subtypes of inhibitory interneuron,chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment(AIS)of targeted pyramidal cells(PCs).However,the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved.Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs,we quantitatively demonstrate that the onset-timing of AIS-GABAergic input,relative to dendritic excitatory glutamatergic inputs,determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC.More specifically,AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+channels on summed synaptic excitation when they precede glutamatergic inputs by15 ms,while for nearly concurrent excitatory inputs,they primarily produce a shunting inhibition at the AIS.Thus,our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.