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

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

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Differing from other subtypes of inhibitory interneuron,chandelier or axo-axonic cells form depolar-izing 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 gluta-matergic 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 gluta-matergic inputs by[15 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.

GABAergic inputsAxon initial segmentSynaptic integrationAxo-axonic cellChandelier cellNEURON simulationDynamic clamp

Ziwei Shang、Junhao Huang、Nan Liu、Xiaohui Zhang

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State Key Laboratory of Cognitive Neuroscience and Learning,IDG/McGovern Institute for Brain Research,Beijing Normal University,Beijing 100875,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaInterdisciplinary Research Fund of Beijing Normal University,China

3213004332071025

2023

10.1007/s12264-022-00887-w

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(1)
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