| Project/Area Number |
23H05478
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Review Section |
Broad Section G
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
McHugh Thomas 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, チームリーダー (50553731)
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| Project Period (FY) |
2023-04-12 – 2028-03-31
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| Project Status |
Granted (Fiscal Year 2024)
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| Budget Amount *help |
¥173,940,000 (Direct Cost: ¥133,800,000、Indirect Cost: ¥40,140,000)
Fiscal Year 2024: ¥34,970,000 (Direct Cost: ¥26,900,000、Indirect Cost: ¥8,070,000)
Fiscal Year 2023: ¥36,010,000 (Direct Cost: ¥27,700,000、Indirect Cost: ¥8,310,000)
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| Keywords | memory / knowledge / schema / learning speed / inference |
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| Outline of Research at the Start |
Although it is well established that pre-existing knowledge impacts the speed and efficacy of new learning, most animal experiments have examined learning in isolation from previous experience. These limitations have precluded our understanding of the circuits and mechanisms underlying the interplay between slow learning in the past and fast learning in the present. Here we will examine how the brain integrates experiences across time and quickly extract regularities. focusing on the use of memory schemas, inferential learning, long-term memory storage and mechanism of fast learning.
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| Outline of Annual Research Achievements |
We have made excellent progress on all four aims of the grant and published one related manuscript during the last fiscal year. The published work (Adaikkan et al, 2024) focused on local circuit control of feedback inhibition in the CA1 region of the hippocampus, related to aim 1 of the project. Ongoing work on all four aims of the project have been progressing nicely and are summarized in more detail below. Anatomical characterization of the noncanonical circuits in aims 1, 2 and 3 is nearly complete and behavioral, electrophysiological and calcium imaging data is currently beging collected. In addition I have presented various aspects of our research progress at multiple international meetings in Germany, Australia, China, Korea, Singapore and Mexico.
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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 work on Aim 1 has gone very smoothly and I anticipate the initial manuscript linking medial septum modulation to learning speed will be published within a year. For Aim2 we have begun in vivo multisite neuropixel 2 recordings in behaving animals and established new useful genetic tools. For Aim 3 we have completed anatomical characterization of layer 5b neurons and identified a behavioral phenotype based on their manipulation. For Aim 4 we continue to refine an optimal behavioral paradigm, however this is expected due to the complexity of the task, and we are now positioned to start the initial manipulation experiments. Overall progress has been excellent.
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| Strategy for Future Research Activity |
In FY2024 we will : Aim1 (learning speed): Focus on the analysis of the physiological and imaging data collected showing septal based modulation of learning speed with the goal of submitting the first manuscript. Aim2 (long term storage) we will continue to collect high-density multisite recording data during learning and consolidation and validate newly engineered virus to specifically target subpopulations of thalamic neurons. Aim 3(inferential learning) Building on our anatomical and behavioral data, we will conduct in vivo imaging of neuronal activity in the hippocampus and entorhinal cortex in behaving mice during manipulation of MEC layer 5b neurons. Aim 4(memory schema) Building on our behavioral paradigm we will begin engram inactivation experiments in the CA1 and the PFC regions.
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