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Elucidating the mechanisms of fast learning

Research Project

Project/Area Number 23H05478
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Review Section Broad Section G
Research InstitutionInstitute of Physical and Chemical Research

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)

Project Period (FY) 2023-04-12 – 2028-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥173,940,000 (Direct Cost: ¥133,800,000、Indirect Cost: ¥40,140,000)
Fiscal Year 2025: ¥34,580,000 (Direct Cost: ¥26,600,000、Indirect Cost: ¥7,980,000)
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)
Keywordsmemory / knowledge / schema / learning speed / inference
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.

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.

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.

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.

Report

(3 results)
  • 2023 Abstract ( PDF )   Comments on the Screening Results   Annual Research Report
  • Research Products

    (9 results)

All 2024 2023 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] MIT(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Indian Institute of Science(インド)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations2024

    • Author(s)
      Adaikkan Chinnakkaruppan、Joseph Justin、Foustoukos Georgios、Wang Jun、Polygalov Denis、Boehringer Roman、Middleton Steven J.、Huang Arthur J. Y.、Tsai Li-Huei、McHugh Thomas J.
    • Journal Title

      Nature Communications

      Volume: 15 Issue: 1 Pages: 2190-2190

    • DOI

      10.1038/s41467-024-46478-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] what does the hippocampal engram encode?2024

    • Author(s)
      Thomas McHugh
    • Organizer
      Winter Conference on Neural Plasticity
    • Related Report
      2023 Annual Research Report
  • [Presentation] Subcortical modulation of hippocampal memory2023

    • Author(s)
      Thomas McHugh
    • Organizer
      LKC School of Medicine Invited Lecture Series
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Subcortical modulation of hippocampal memory2023

    • Author(s)
      Thomas McHugh
    • Organizer
      Guangyang Bay Conference on Brain and Intelligence
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] hippocampal memory: engrams, inhibition & oscillations2023

    • Author(s)
      Thomas McHugh
    • Organizer
      NEURONAL REPRESENTATION: FROM SYNAPSES & MICROCIRCUITS TO BEHAVIOR
    • Related Report
      2023 Annual Research Report
  • [Presentation] cortical-hippocampal interactions across learning2023

    • Author(s)
      Thomas McHugh
    • Organizer
      The International Conference on Learning and Memory
    • Related Report
      2023 Annual Research Report
  • [Presentation] impact of bidirectional manipulation of local dendrite-targeting interneurons on hippocampal memory formation2023

    • Author(s)
      Thomas McHugh
    • Organizer
      IMC20
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2023-04-13   Modified: 2025-04-17  

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