The entorhinal cortex modulates trace fear memory formation and neuroplasticity in the mouse lateral amygdala via cholecystokinin

  1. Hemin Feng
  2. Junfeng Su
  3. Wei Fang
  4. Xi Chen
  5. Jufang He  Is a corresponding author
  1. City University of Hong Kong, Hong Kong

Abstract

Although fear memory formation is essential for survival and fear-related mental disorders, the neural circuitry and mechanism are incompletely understood. Here, we utilized trace fear conditioning to study the formation of trace fear memory in mice. We identified the entorhinal cortex (EC) as a critical component of sensory signaling to the amygdala. We adopted both loss-of-function and gain-of-function experiments to demonstrate that release of the cholecystokinin (CCK) from the EC is required for trace fear memory formation. We discovered that CCK-positive neurons project from the EC to the lateral nuclei of the amygdala (LA), and inhibition of CCK-dependent signaling in the EC prevented long-term potentiation of the auditory response in the LA and formation of trace fear memory. In summary, high-frequency activation of EC neurons triggers the release of CCK in their projection terminals in the LA, potentiating auditory response in LA neurons. The neural plasticity in the LA leads to trace fear memory formation.

Data availability

Data for this submission has been uploaded to the Dryad Digital Repository,available once published: doi:10.5061/dryad.0p2ngf217

The following data sets were generated

Article and author information

Author details

  1. Hemin Feng

    Department of Neuroscience, City University of Hong Kong, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  2. Junfeng Su

    Department of Neuroscience, City University of Hong Kong, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  3. Wei Fang

    Department of Neuroscience, City University of Hong Kong, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
  4. Xi Chen

    Departments of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2144-6584
  5. Jufang He

    Department of Neuroscience, City University of Hong Kong, Kowloon, Hong Kong
    For correspondence
    jufanghe@cityu.edu.hk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4288-5957

Funding

Hong Kong Research Grants Council (T13-605/18-W,11102417M,11101818M,11103220)

  • Jufang He

Natural Science Foundation of China (31671102)

  • Jufang He

Health and Medical Research Fund (06172456,31571096)

  • Jufang He

Innovation and Technology Fund (MRP/101/17X,MPF/053/18X,GHP_075_19GD)

  • Jufang He

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental procedures were approved by the Animal Subjects Ethics Sub-Committee of the City University of Hong Kong (Reference number of animal ethics review: A-0529 and A-0282)

Reviewing Editor

  1. Joshua Johansen, RIKEN Center for Brain Science, Japan

Version history

  1. Received: April 12, 2021
  2. Preprint posted: April 18, 2021 (view preprint)
  3. Accepted: November 12, 2021
  4. Accepted Manuscript published: November 15, 2021 (version 1)
  5. Version of Record published: November 29, 2021 (version 2)

Copyright

© 2021, Feng et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Hemin Feng
  2. Junfeng Su
  3. Wei Fang
  4. Xi Chen
  5. Jufang He
(2021)
The entorhinal cortex modulates trace fear memory formation and neuroplasticity in the mouse lateral amygdala via cholecystokinin
eLife 10:e69333.
https://doi.org/10.7554/eLife.69333

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https://doi.org/10.7554/eLife.69333

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