2022 Fiscal Year Research-status Report
Revealing the Role of Postnatal Theta Rhythm in Establishing Memory Consolidation Mechanism during REM Sleep
| Project/Area Number |
21K06419
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Kumar Deependra 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (20747696)
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| Co-Investigator(Kenkyū-buntansha) |
船戸 弘正 筑波大学, 国際統合睡眠医科学研究機構, 客員教授 (90363118)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | Sleep / memory / Theta / hippocampus / neonates / TRAP2 / Dreamless / Fear expression |
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| Outline of Annual Research Achievements |
We found dreamless mice display low freezing behavior during fear conditioning, which could be due to chronic loss of REM sleep. Early data indicates their REM sleep duration gets further shortened during the postconditioning sleep, which can influence the memory consolidation. Furthermore, hippocampal theta shows low spectral power during REM sleep, that required for memory storage.
Indeed dreamless show low-freezing behavior one day or two weeks later. Dreamless shows a larger loss of memory at two weeks time, indicating faster memory decay compared with wild type littermates . Upon remote memory retrieval, the number of c-fos positive cells in the anterior cingulate cortex (ACC), a center for remote memory storage, was low in dreamless, which agrees with lower freezing behavior.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
Customized tetrode required to measure LFP in the neonatal brain is established.
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| Strategy for Future Research Activity |
In mutant mice, LFP will be measured simultaneously from the medial septum (theta generator) and hippocampus (prominent theta in REM) to narrow the region and cause-related with low theta in mutant mice.
Theta synchronicity between the hippocampus, amygdala, and medial prefrontal cortex is essential for memory task performance. LFP will be measured during fear learning, sleep, and memory retrieval period.
Can theta wave enhancement rescue fear memory in mutant mice? To test, dreamless mutants expressing channelrhodopsin in medial septum cholinergic neurons will receive laser light to induce hippocampal theta during task performance and sleep artificially.
How does theta enhancement affect the activity of learning tag cells? Imaging and optogenetics techniques will be combined to understand theta's role in the consolidation mechanism.
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| Causes of Carryover |
We need to procure consumables items for optogenetics and LFP/EEG/EMG surgery. For example, optic fibre, platinum-iridium wire for preparing tetrode, miniature EEG screw for neonates, dental cement and solution, IC sockets, etc.
The imaging experiment requires a sufficient number of green lenses (inscopix) and baseplates, which are not reusable. Up to three dummy microscopes are needed for habituation purposes.
Antibodies (RFP, FOS, GFP, DCx, and ChAT) for immunohistochemistry and Tamoxifen for tagging activated cell is required. Several types of primers for genotyping various transgenic mice are needed.
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[Journal Article] Kinase signalling in excitatory neurons regulates sleep quantity and depth2022
Author(s)
Kim SJ, Hotta-Hirashima N, Asano F, Kitazono T, Iwasaki K, Nakata S, Komiya H, Asama N, Matsuoka T, Fujiyama T, Ikkyu A, Kakizaki M, Kanno S, Choi J, Kumar D, Tsukamoto T, Elhosainy A, Mizuno S, Miyazaki S, Tsuneoka Y, Sugiyama F, Takahashi S, Hayashi Y, Muratani M, Liu Q, Miyoshi C, Yanagisawa M, Funato H.
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Journal Title
Nature
Volume: 612
Pages: 512-518
DOI
Peer Reviewed / Int'l Joint Research
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