Abstract
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.
基金项目
National Natural Science Foundation of China(32130043)
National Natural Science Foundation of China(32071025)
Interdisciplinary Research Fund of Beijing Normal University,China()
维普
万方数据