Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment.
10.1007/s12264-022-00887-w
- Author:
Ziwei SHANG
1
;
Junhao HUANG
1
;
Nan LIU
1
;
Xiaohui ZHANG
2
Author Information
1. State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.
2. State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China. xhzhang@bnu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Axo-axonic cell;
Axon initial segment;
Chandelier cell;
Dynamic clamp;
GABAergic inputs;
NEURON simulation;
Synaptic integration
- MeSH:
Axon Initial Segment;
Axons/physiology*;
Neurons;
Synapses/physiology*;
Pyramidal Cells/physiology*;
Interneurons/physiology*;
Action Potentials/physiology*
- From:
Neuroscience Bulletin
2023;39(1):1-13
- CountryChina
- Language:English
-
Abstract:
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 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.
