Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks
Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks
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DOI：
10.1111/jnc.14938
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发表时间：
2019-12-29
影响因子：
4.7
通讯作者：
Dzakpasu, Rhonda
中科院分区：
文献类型：
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作者：
Djemil, Sarra;Chen, Xin;Dzakpasu, Rhonda
已知烟碱型乙酰胆碱受体（nAChR）在海马的认知功能中起作用，例如记忆巩固。考虑到它们传导Ca 2+并能够调节海马内谷氨酸和γ-氨基丁酸（GABA）的释放，从而改变兴奋-抑制比，我们假设nAChRs的激活将导致海马网络的增强并改变同步。我们使用尼古丁作为一种工具，以探讨nAChRs的激活对神经元网络动力学的影响，在原代胚胎大鼠海马培养从定时怀孕的Sprague-Dawley大鼠。我们扰动培养的海马网络与增加浓度的浴应用尼古丁和进行网络细胞外记录的动作电位使用微电极阵列。我们发现尼古丁以浓度依赖性方式调节网络动力学;它增强了动作电位的放电，并促进了爆发活动。此外，我们使用药理学试剂来确定离散的nAChR亚型对所观察到的网络动态的贡献。我们发现，含β 4的nAChRs是观察到的尖峰，爆发和同步性增加所必需的，而α 7 nAChRs的激活增强尼古丁介导的网络增强，但不是必要的表现。我们还观察到N-甲基-D-天冬氨酸受体（NMDAR）和I组代谢型谷氨酸受体（mGluRs）的拮抗剂部分阻断尼古丁的作用。此外，尼古丁暴露促进Ca 2 +/钙调蛋白依赖性激酶II（CaMKII）的自磷酸化和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）亚基GluA 1的丝氨酸831磷酸化。这些结果表明，烟碱受体诱导的增强和同步化的海马网络和突触传递。这项工作的发现突出了胆碱能信号在产生网络范围内的增强作用的影响，增强的尖峰和爆发动力学的形式，与记忆的分子相关性，如增加磷酸化的CaMKII和GluA 1。这篇文章获得了 *Open Materials* 的徽章，因为它提供了所有相关信息来复制手稿中的研究。有关开放实践徽章的更多信息，请访问
Nicotinic acetylcholine receptors (nAChRs) are known to play a role in cognitive functions of the hippocampus, such as memory consolidation. Given that they conduct Ca2+ and are capable of regulating the release of glutamate and gamma-aminobutyric acid (GABA) within the hippocampus, thereby shifting the excitatory-inhibitory ratio, we hypothesized that the activation of nAChRs will result in the potentiation of hippocampal networks and alter synchronization. We used nicotine as a tool to investigate the impact of activation of nAChRs on neuronal network dynamics in primary embryonic rat hippocampal cultures prepared from timed-pregnant Sprague-Dawley rats. We perturbed cultured hippocampal networks with increasing concentrations of bath-applied nicotine and performed network extracellular recordings of action potentials using a microelectrode array. We found that nicotine modulated network dynamics in a concentration-dependent manner; it enhanced firing of action potentials as well as facilitated bursting activity. In addition, we used pharmacological agents to determine the contributions of discrete nAChR subtypes to the observed network dynamics. We found that beta 4-containing nAChRs are necessary for the observed increases in spiking, bursting, and synchrony, while the activation of alpha 7 nAChRs augments nicotine-mediated network potentiation but is not necessary for its manifestation. We also observed that antagonists of N-methyl-D-aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs) partially blocked the effects of nicotine. Furthermore, nicotine exposure promoted autophosphorylation of Ca2+/calmodulin-dependent kinase II (CaMKII) and serine 831 phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit GluA1. These results suggest that nicotinic receptors induce potentiation and synchronization of hippocampal networks and glutamatergic synaptic transmission. Findings from this work highlight the impact of cholinergic signaling in generating network-wide potentiation in the form of enhanced spiking and bursting dynamics that coincide with molecular correlates of memory such as increased phosphorylation of CaMKII and GluA1. Open science badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. More information about the Open Practices badges can be found at