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May, 2023;39 (5): 731-744.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal Networks.

Xiao-Wei Li, Yi Ren, Dong-Qing Shi, Lei Qi, Fang Xu, Yanyang Xiao, Pak-Ming Lau, Guo-Qiang Bi
Author Information
  1. Xiao-Wei Li: CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China. ORCID
  2. Yi Ren: CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China.
  3. Dong-Qing Shi: CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China. ORCID
  4. Lei Qi: CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China.
  5. Fang Xu: CAS Key Laboratory of Brain Connectome and Manipulation, Interdisciplinary Center for Brain Information, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.
  6. Yanyang Xiao: CAS Key Laboratory of Brain Connectome and Manipulation, Interdisciplinary Center for Brain Information, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China. yy.xiao@siat.ac.cn.
  7. Pak-Ming Lau: CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China. plau@ustc.edu.cn. ORCID
  8. Guo-Qiang Bi: CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China. ORCID
PMID: 36670292 DOI: 10.1007/s12264-022-01012-7

Abstract

Acetylcholine (ACh) is an important neuromodulator in various cognitive functions. However, it is unclear how ACh influences neural circuit dynamics by altering cellular properties. Here, we investigated how ACh influences reverberatory activity in cultured neuronal networks. We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses, but to a much lesser extent at high doses. Moreover, high doses of ACh caused a longer duration of evoked reverberation, and a higher occurrence of spontaneous activity. With whole-cell recording from single neurons, we found that ACh inhibited excitatory postsynaptic currents (EPSCs) while elevating neuronal firing in a dose-dependent manner. Furthermore, all ACh-induced cellular and network changes were blocked by muscarinic, but not nicotinic receptor antagonists. With computational modeling, we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations. Thus, ACh modulates network dynamics in a biphasic fashion, probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

Keywords

Acetylcholine Excitability Neuronal network Reverberation Synaptic current

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MeSH Term

Cholinergic Agents
Acetylcholine
Neurons
Synaptic Transmission

Chemicals

Cholinergic Agents
Acetylcholine
Journal Article
Article has an altmetric score of 1

Word Cloud

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