Kim Chae Young, Kim Sang Jeong, Kloosterman Fabian
Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.
NERF, Leuven 3000, Belgium.
Exp Neurobiol. 2022 Jun 30;31(3):208-220. doi: 10.5607/en22011.
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.
海马体尖波涟漪活动（SWRs）以及相关的神经活动模式重放在记忆巩固中的作用广为人知。由于需要高时间分辨率来识别神经元信号中的SWRs，因此一直使用电生理方法来研究这种活动。然而，分析神经元对特定任务SWRs的个体贡献一直很困难，因为用电生理记录很难长时间跟踪神经元。在本研究中，我们记录了自由活动小鼠海马体CA1区的局部场电位（LFP）信号，并同时对同侧CA1区的钙信号进行成像，以利用电生理和成像方法的优势。我们制作了一个定制设计的微驱动阵列，将四极管靶向左侧海马体CA1区进行LFP记录，并在腹侧海马连合（VHC）施加电刺激以闭环破坏SWRs。使用微型荧光显微镜（Miniscope）和基因编码钙指示剂对右侧海马体CA1区的神经元群体进行成像。由于SWRs显示出高度同步的双侧发生，因此在自发或SWRs被破坏的情况下，可以识别和跟踪参与SWRs的神经元的钙信号。使用这种方法，我们确定了一个CA1神经元亚群，其显示出与SWRs同步的钙升高。我们的结果表明，与非SWR相关的钙瞬变相比，电刺激对SWR相关的钙瞬变破坏更大，这验证了该系统检测和破坏SWRs的能力。我们的双记录方法可用于揭示单个神经元在SWRs中的动态参与以及在延长的时间窗口内的重放。
