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作 者:Xiao-Wei Li Yi Ren Dong-Qing Shi Lei Qi Fang Xu Yanyang Xiao Pak-Ming Lau Guo-Qiang Bi
机构地区:[1]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 [2]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
出 处:《Neuroscience Bulletin》2023年第5期731-744,共14页神经科学通报(英文版)
基 金:supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32030200);the National Natural Science Foundation of China(31070935 and 62173326);the National Basic Research Program of China(2013CB835100);the Youth Innovation Promotion Association,CAS(2022367)。
摘 要:Acetylcholine(ACh)is an important neuromod-ulator in various cognitive functions.However,it is unclear how ACh influences neural circuit dynamics by altering cellular properties.Here,we investigated how ACh influ-ences 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 occur-rence of spontaneous activity.With whole-cell recording from single neurons,we found that ACh inhibited excita-tory postsynaptic currents(EPSCs)while elevating neu-ronal 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.
关 键 词:ACETYLCHOLINE Neuronal network REVERBERATION Synaptic current EXCITABILITY
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