| 研究課題/領域番号 |
19H05646
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| 研究機関 | 国立研究開発法人理化学研究所 |
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研究代表者 |
McHugh Thomas 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (50553731)
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| 研究期間 (年度) |
2019-06-26 – 2024-03-31
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| キーワード | hippocampus / cortex / engram / memory / oscillations |
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| 研究実績の概要 |
Related to Aim 3 of the proposal, we recently published our initial findings on the identification of a physiological signature of memory age in the prefrontal-hippocampal circuits (Makino et al, 2019). In that study we performed simultaneous electrophysiological recordings from anterior cingulate cortex (ACC) and hippocampal CA1 in mice during recall of recent and remote contextual fear memory and found that in contrast to recent memory, remote recall was accompanied by increased ACC-CA1 synchronization at multiple frequency bands. Our findings revealed that memory consolidation alters the dynamic coupling of the prefrontal-hippocampal circuit and results in a physiological signature of memory age. Next, this project has contributed to a second significant achievement, a study published in Nature in late 2020 (Chen et al.). Although that study began prior to the adoption of the current grant, it focused on novelty detection and memory encoding and the methodological approaches developed in this project, namely transgenic cFos labeling and optogenetic cell identification techniques, were key to the successful completion of this work. Moreover, these data have led to our incorporation of understanding novelty signaling and its influence on the hippocampal engram neurons into the goals of the project.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Despite the challenges accompanying the world-wide COVID-19 pandemic, detailed in section 9 above, I feel our research progress remains on schedule and we are fully capable of reaching our objectives. We have already published two manuscripts, a Cell Reports paper directly related to Aim 3 of this project and a study in Nature, which began outside of the scope of the original plan, but due to technology development spurred by the project, has proven highly synergistic to our ongoing work. The main finding in that study is the identification of parallel hypothalamic circuits that can signal novelty to the dorsal hippocampus. This identification of a hitherto unidentified novelty circuit in the mammalian brain has motivated us to understand the impact of these circuits on hippocampal physiology and memory dynamics in our future experiments. Further, despite the challenges in data collection and personnel the last year, our progress on both short and long-term goals is on track. I anticipate four studies will be published in the next fiscal year, two related to the circuit mechanisms of temporal coordination of memory reactivation in the hippocampus and two examining the impact of disease and stress on the dynamics of memory. The next stage of large scale data collection is ready to begin in FY2021 and should position us well to reach our objectives and publish our results in the final two years of the project.
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| 今後の研究の推進方策 |
To achieve the aims of this project we have added several important features to our experimental approaches over the last year, including the incorporation of custom software built on the Neuralynx Hardware Processing Platform which allows real-time detection of physiological events on-line (such as ripples; 120-180Hz oscillation in the CA1 LFP) and subsequent triggering of lasers for time-locked optogenetic intervention with millisecond precision, as well as the further development of transgenic and viral-based methods for activity-dependent cell labeling using both the cFos and Npas4 promoter systems. As described in the research results below, these advances, in combination with our established expertise in specific neuronal and circuit manipulations and high density activity monitoring, have allowed us to identify small populations of neurons involved in the encoding or modulation of memories or behaviors and analyze their circuit connectivity and function.
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