2021 Fiscal Year Final Research Report

Rescuing impaired learning in a mouse model for autism

Research Project

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Project/Area Number	19H03553
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 51030:Pathophysiologic neuroscience-related
Research Institution	Institute of Physical and Chemical Research
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)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	Hippocampus / Prefrontal cortex / Memory / Autism / Sharp-wave ripples
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
Free Research Field	Neurosciecne
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