Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks

作者：Sarra Djemil, Xin Chen, Ziyue Zhang, Jisoo Lee, Mikael Rauf, Daniel T.S. Pak, Rhonda Dzakpasu · 发表于：Journal of Neurochemistry · 年份：2019 · DOI：10.1111/jnc.14938 · 被引用次数：11 · 研究领域：Nicotinic Acetylcholine Receptors Study、Neuroscience and Neuropharmacology Research、Photoreceptor and optogenetics research

Abstract 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 γ‐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 β4‐containing nAChRs are necessary for the observed increases in spiking, bursting, and synchrony, while the activation of α7 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 ...