Hippocampal sharp-wave ripple activity (SWRs) and the associated replay of neural activity patterns are well-known for their role in memory consolidation. This activity has been studied using electrophysiological approaches, as high temporal resolution is required to recognize SWRs in the neuronal signals. However, it has been difficult to analyze the individual contribution of neurons to task-specific SWRs, because it is hard to track neurons across a long time with electrophysiological recording. In this study, we recorded local field potential (LFP) signals in the hippocampal CA1 of freely behaving mice and simultaneously imaged calcium signals in contralateral CA1 to leverage the advantages of both electrophysiological and imaging approaches. We manufactured a custom-designed microdrive array and targeted tetrodes to the left hippocampus CA1 for LFP recording and applied electrical stimulation in the ventral hippocampal commissure (VHC) for closed-loop disruption of SWRs. Neuronal population imaging in the right hippocampal CA1 was performed using a miniature fluorescent microscope (Miniscope) and a genetically encoded calcium indicator. As SWRs show highly synchronized bilateral occurrence, calcium signals of SWR-participating neurons could be identified and tracked in spontaneous or SWR-disrupted conditions. Using this approach, we identified a subpopulation of CA1 neurons showing synchronous calcium elevation to SWRs. Our results showed that SWR-related calcium transients are more disrupted by electrical stimulation than non-SWRrelated calcium transients, validating the capability of the system to detect and disrupt SWRs. Our dual recording method can be used to uncover the dynamic participation of individual neurons in SWRs and replay over extended time windows.

中文翻译：

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自由行为小鼠的同时细胞成像、电记录和海马活动刺激。

海马尖波波纹活动 (SWR) 和相关的神经活动模式重放以其在记忆巩固中的作用而闻名。已经使用电生理学方法研究了这种活动，因为需要高时间分辨率来识别神经元信号中的 SWR。然而，很难分析神经元对特定任务 SWR 的个体贡献，因为很难通过电生理记录长时间跟踪神经元。在这项研究中，我们记录了自由行为小鼠海马 CA1 中的局部场电位 (LFP) 信号，并同时在对侧 CA1 中成像钙信号，以利用电生理学和成像方法的优势。我们制造了一个定制设计的微驱动器阵列，并将 tetrodes 定位到左侧海马 CA1 用于 LFP 记录，并在腹侧海马连合 (VHC) 中应用电刺激以实现 SWR 的闭环中断。使用微型荧光显微镜 (Miniscope) 和基因编码的钙指示剂进行右侧海马 CA1 中的神经元群体成像。由于 SWR 显示出高度同步的双边发生，因此可以在自发或 SWR 中断的条件下识别和跟踪 SWR 参与神经元的钙信号。使用这种方法，我们确定了一个 CA1 神经元亚群，显示出与 SWR 同步的钙升高。我们的结果表明，与非 SWR 相关的钙瞬变相比，与 SWR 相关的钙瞬变更容易受到电刺激的破坏，验证系统检测和中断 SWR 的能力。我们的双重记录方法可用于揭示单个神经元在 SWR 中的动态参与，并在延长的时间窗口内回放。