The Firing of Theta State-Related Septal Cholinergic Neurons Disrupt Hippocampal Ripple Oscillations via Muscarinic Receptors
The Firing of Theta State-Related Septal Cholinergic Neurons Disrupt Hippocampal Ripple Oscillations via Muscarinic Receptors
复制标题
与 Theta 状态相关的间隔胆碱能神经元的放电通过毒蕈碱受体扰乱海马波纹振荡
DOI：
10.1523/jneurosci.1568-19.2020
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发表时间：
2020-04-29
影响因子：
5.3
通讯作者：
Xu，Jiamin
中科院分区：
文献类型：
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作者：
Ma，Xiaoyu;Zhang，Yiyao;Xu，Jiamin
隔海胆碱能系统对海马体的学习和记忆至关重要。然而，对中隔胆碱能神经元的体内放电模式和生理功能的定量描述仍然缺失。在这项研究中，我们将光遗传学与多通道体内记录相结合，记录了自由行为雄性小鼠5.5-72 h的MS胆碱能神经元放电活动，我们发现它们的放电活动与海马theta状态高度相关。MS胆碱能神经元在theta优势期（如主动探索和快速眼动睡眠）高度活跃，而在非theta期（如慢波睡眠）几乎沉默。有趣的是，在SWS期间，这些MS胆碱能神经元的光遗传激活抑制了CA1纹波振荡。这种抑制可通过毒蕈碱M2或M4受体拮抗剂恢复。这些结果表明MS胆碱能神经元具有以下重要的生理功能：通过在θ波时期持续放电来维持高水平的海马乙酰胆碱水平，从而抑制波纹并使θ波振荡占主导地位。意义：海马中乙酰胆碱的主要来源是内侧隔。早期实验发现，MS病变导致海马theta振荡消失，由此推测中隔-海马胆碱能投射导致theta振荡。在本文中，通过长期记录MS胆碱能神经元，我们发现它们表现出与θ波状态相关的放电模式。然而，光遗传学激活这些神经元对海马的θ节律几乎没有影响。相反，我们发现在慢波睡眠期间激活MS胆碱能神经元可以抑制海马纹波振荡。这种抑制是由毒蕈碱M2和M4受体介导的。
The septo-hippocampal cholinergic system is critical for hippocampal learning and memory. However, a quantitative description of the in vivo firing patterns and physiological function of medial septal (MS) cholinergic neurons is still missing. In this study, we combined optogenetics with multichannel in vivo recording and recorded MS cholinergic neuron firings in freely behaving male mice for 5.5–72 h. We found that their firing activities were highly correlated with hippocampal theta states. MS cholinergic neurons were highly active during theta-dominant epochs, such as active exploration and rapid eye movement sleep, but almost silent during non-theta epochs, such as slow-wave sleep (SWS). Interestingly, optogenetic activation of these MS cholinergic neurons during SWS suppressed CA1 ripple oscillations. This suppression could be rescued by muscarinic M2 or M4 receptor antagonists. These results suggest the following important physiological function of MS cholinergic neurons: maintaining high hippocampal acetylcholine level by persistent firing during theta epochs, consequently suppressing ripples and allowing theta oscillations to dominate. SIGNIFICANCE STATEMENT The major source of acetylcholine in the hippocampus comes from the medial septum. Early experiments found that lesions to the MS result in the disappearance of hippocampal theta oscillation, which leads to speculation that the septo-hippocampal cholinergic projection contributing to theta oscillation. In this article, by long-term recording of MS cholinergic neurons, we found that they show a theta state-related firing pattern. However, optogenetically activating these neurons shows little effect on theta rhythm in the hippocampus. Instead, we found that activating MS cholinergic neurons during slow-wave sleep could suppress hippocampal ripple oscillations. This suppression is mediated by muscarinic M2 and M4 receptors.