| Project/Area Number |
19H03553
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Middleton Steven 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, 研究員 (60526797)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Keywords | Hippocampus / Prefrontal cortex / Memory / Autism / Sharp-wave ripples / SCN2A / hippocampus / memory / autism / disease / rescue / learning / Sharp- wave ripples |
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| Outline of Research at the Start |
The key purpose of this research is to understand the neural basis of learning and how this is altered in autism. We will study two brain regions that are key for the learning (prefrontal cortex and hippocampus) and how they differ in a transgenic mouse model of autism.
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| Outline of Final Research Achievements |
This project aims to reverse the impaired learning in a mouse model of autism. To address this I first aimed to characterize in detail the differences between normal and the autism model mice, in two specific brain areas (hippocampus and prefrontal cortex) that are important in working memory tasks. Here, I found in line with the original first hypothesis, that in normal healthy mice, a specific type of activity that occurs in the brain called sharp-wave ripples have a dual role with respect to learning. When animals make a correct vs an incorrect decision, activity within the brain networks that connect these two areas change in a systematic way, dependent on the trial outcome. However, in line with hypothesis 2, when the same experiments are done in the autism model mice the networks appear to be overly rigid, meaning that sharp-wave ripples cannot reconfigure the connections between the neurons appropriately, explaining why learning is impaired. The remaining data is being analysed
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| Academic Significance and Societal Importance of the Research Achievements |
This project demonstrates that by using large scale recording of neural activity and using the appropriate analytical techniques to understand the interaction of multiple brain regions, we can better understand disease states. Moreover, the results and follow up work aim to explore better treatments
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