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Mechanisms of memory consolidation during sleep

Our brains perform various processes during sleep, such as consolidating necessary memories and regulating emotional responses to unpleasant memories. Our laboratory is studying memory processing during sleep in two directions. The first is studying how neurons that continue to regenerate in the adult brain consolidate memories during sleep (Kumar et al., Neuron, 2020, etc.). This research aims to contribute to future technologies for functional reconstruction of neural circuits lost in Alzheimer's disease. Second, we are investigating techniques to facilitate the processing of fear memories by sound during sleep (Purple et al., Sci Rep, 2017). Based on the achivements of those basic research, we are currently conducting a clinical study with PTSD patients. This research aims to demonstrate that PTSD can be treated during sleep and to develop a new technology that would allow patients suffering from traumatic memories to be treated at home.

For these research, we utilizes in vivo calcium imaging using original miniscope (Srinivasan,et al., BBRC 2019), optogenetics (Kumar et al., Neuron, 2020) and AI-assisted full-automatic real-time sleep stage specific interevention (Tezuka et al., Sci Rep, 2021). Our sthrength is to be able to integrate these technique to provide solid causal evidence between neuronal activities and behavioral changes.

 

Integration of adult-born neurons into memory circuitry during sleep

In contrast to other brain regions in which neurogenesis is terminated at adulthood, the dentate gyrus of the hippocampus continues to generate new neurons across the human lifespan (e.g., Eriksson et al., Nat. Med., 1998). Several lines of evidence indicate that adult-born neurons can be used to regenerate damaged brain tissue (Sakaguchi and Okano, Dev. Neurobiol., 2012). To utilize adult-born neurons in clinical settings, it is essential to understand how new neurons integrate into existing neuronal circuits.

Previous studies suggest that sleep is important for memory formation. For example, neurons that are activated during learning are re-activated during sleep (e.g., Wilson and McNaughton, Science, 1994). This reactivation is thought to be responsible for memory consolidation. However, evidence that adult-born neurons participate in memory formation during specific stages of sleep was lacking. In rodents, each sleep episode is very short in duration, (e.g., REM occurs for 60 seconds on average), making sleep stage-specific investigation of the function of adult-born neurons technically challenging.

Our group has overcome these challenges by utilizing the advanced techniques of optogenetics to manipulate adult-born neurons during specific stage of sleep and found that sparse activity of the adult-born neurons is necessary for memory consolidation during REM sleep (Kumar et al., Neuron, 2020).
Our goal is to further clarify the mechanisms by which adult-born neurons integrate into memory circuitry during sleep, which could contribute to the prevention or treatment of neurodegenerative diseases.


 

 

睡眠中の記憶処理メカニズムの解明

私たちの脳は、睡眠中に必要な記憶を定着したり、嫌な記憶に対して生じる感情の反応を調整したりと、様々な処理を行っています。私たちの研究室では二つの方向性で睡眠中の記憶処理の研究を行っています。一つ目は、成体脳で再生を続けるニューロンが、睡眠中に記憶を固定化する仕組みを研究しています (Kumar et al,. Neuron, 2020など)。この研究は将来、アルツハイマー病などで失われた神経回路の機能的な再建技術に貢献することを目指しています。二つ目は、睡眠中に音によって恐怖記憶の処理を促進する技術の研究をしています(Purple et al., Sci Rep, 2017)。さらにこれらの基礎研究成果を応用することで、PTSDの新しい治療法の技術開発を目指した臨床研究を行っています。見学や短期訪問も可能ですので、お気軽にメール等でお問い合わせください。

 

研究案内はこちら(日本語)

 

ユーチューブ番組はこちら(日本語)