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Elucidating the circuits of functional lateralization in the hippocampus

Research Project

Project/Area Number 22K15234
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Guan Hefei  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, 特別研究員 (00930273)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Granted (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsSpatial memory / Hippocampus / Lateralization / Memory mechanisms
Outline of Research at the Start

I'll test whether left and right CA3 play distinct and complementary roles in memory which will be a significant step forward in the field, demonstrating that functional lateralization in the hippocampal circuit is evolutionary conserved across rodents and humans.

Outline of Annual Research Achievements

The first stage of the project involved characterizing the inhibitory effects and time course of viral expression of Gi-DREADD and KOR-DREADD in the hippocampus, as well as examining their corresponding ligand effects on in vivo hippocampal activity.
For the second stage, behavioral tasks were conducted to investigate the different functions of the left and right CA3 regions in spatial navigation and memory. In the object location test, mice were trained with two familiar objects, and during the second session of recall, one of the objects was moved to a different location after the left CA3 was silenced instead of the right CA3. The mice spent more time exploring the object in the novel location, which is attributed to their innate preference for novelty. These findings suggest that the left CA3 region is more crucial for the acquisition of spatial memory.

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 research project is progressing relatively smoothly. The planned assessment of DREADD-mediated silencing of neural activity in the bilateral hippocampus has been completed as scheduled, as have the behavioral tasks designed to test the spatial navigation and memory functions of the left and right CA3 regions. However, there has been a delay in starting the in vivo recording experiment due to the late delivery of a camera necessary for detecting animal behavior in the object location test. We are expecting to receive the new camera soon, and to ensure that we stay on track with the planned schedule, a part-time student has been hired to assist with the preparation of the recording experiment.

Strategy for Future Research Activity

As outlined in the grant proposal, the first step of the study will be to investigate whether the output of the left and right CA3 regions plays differential roles in the coordination of bilateral CA1 spatial coding. This will be achieved by injecting different viruses in the left and right CA3 regions and recording simultaneously in the bilateral CA1 regions while mice navigate a linear track.
Additionally, the study will involve recording from bilateral CA1 regions while mice perform object location tasks, in order to further understand the mechanisms underlying the differences between the left and right CA3 regions in spatial memory. I will adhere to the plan outlined in the grant proposal throughout the study.

Report

(1 results)
  • 2022 Research-status Report
  • Research Products

    (1 results)

All 2023

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results)

  • [Journal Article] The expanded circuitry of hippocampal ripples and replay2023

    • Author(s)
      He Hongshen、Guan Hefei、McHugh Thomas J.
    • Journal Title

      Neuroscience Research

      Volume: 189 Pages: 13-19

    • DOI

      10.1016/j.neures.2022.12.010

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research

URL: 

Published: 2022-04-19   Modified: 2023-12-25  

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