2020 Fiscal Year Annual Research Report
Rescuing impaired learning in a mouse model for autism
| Project/Area Number |
19H03553
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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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| Keywords | Hippocampus / Prefrontal cortex / SCN2A / Autism |
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| Outline of Annual Research Achievements |
Data has been collected for the first two goals of the proposed grant. The bulk of this data has already been analysed and indeed we find patterns of activity in control mice that differentiate correct from incorrect trials in control mice. These changes are so consistent that we are able to decode the outcome of a trial (either success or failure) based on changes that occur within the hippocampo-cortico network. Our analysis of the data from SCN mice, shows that this is not the case in this group and we are unable to reliably predict trial outcome, based on changes occurring within the network. Our data suggest these mice are unable to reliably update the network in response to correct or incorrect trials in an appropriate manner, which leads to the impaired learning phenotype they show.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The current status of the research is approximately in line with the original plan outlined in the proposal. There has been a slight delay in the experimental schedule, due to the pandemic which led to some delays in acquiring equipment and experiments having to be scheduled appropriately to minimize social contact within the laboratory. However, the progress of the project is still almost exactly where it had been projected to be at this stage in the proposal. We envisage any slight delays that were incurred owing to the restrictions from COVID, can easily be made up in the next year.
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| Strategy for Future Research Activity |
The plan for the upcoming year will be to complete goal 3 of the original proposal which involves manipulating the activity of the neurons in SCN2A mice with the DREADD system in order to rescue the learning deficits we observe. This will involve virally expressing the DREADD receptors in a cell type specific manner in SCN2A, which will then allow us to artificially upregulate or downregulate their activity. At the same time, the activity of the neurons will be recorded in both hippocampus and prefrontal cortex. This will allow us to establish if this manipulation, restores the ability of the network to appropriately update itself, depending on the outcome of a learning trial. We are currently preparing a manuscript detailing the findings related to goals 1&2.
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