Early life adversity decreases pre-adolescent fear expression by accelerating amygdala PV cell development

Abstract

Early life adversity (ELA) is associated with increased risk for stress-related disorders later in life. The link between ELA and risk for psychopathology is well established but the developmental mechanisms remain unclear. Using a mouse model of resource insecurity, limited bedding (LB), we tested the effects of LB on the development of fear learning and neuronal structures involved in emotional regulation, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). LB delayed the ability of peri-weanling (21 days old) mice to express, but not form, an auditory conditioned fear memory. LB accelerated the developmental emergence of parvalbumin (PV) positive cells in the BLA and increased anatomical connections between PL and BLA. Fear expression in LB mice was rescued through optogenetic inactivation of PV positive cells in the BLA. The current results provide a model of transiently blunted emotional reactivity in early development, with latent fear-associated memories emerging later in adolescence.

Data availability

Data has been deposited in the Brown Digital Repository with the following DOI: https://doi.org/10.26300/9krc-h052

The following data sets were generated

Article and author information

Author details

  1. Gabriela Manzano Nieves

    Neuroscience, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marilyn Bravo

    Neuroscience, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Saba Baskoylu

    Neuroscience, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kevin G Bath

    Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, United States
    For correspondence
    Kevin_Bath@Brown.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2229-177X

Funding

National Institutes of Health (MH115914)

  • Kevin G Bath

National Institutes of Health (MH115049)

  • Kevin G Bath

National Institutes of Health (NS105219)

  • Gabriela Manzano Nieves

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#19-10-0003) of Brown University.

Reviewing Editor

  1. Matthew N Hill, University of Calgary, Canada

Version history

  1. Received: January 17, 2020
  2. Accepted: July 20, 2020
  3. Accepted Manuscript published: July 21, 2020 (version 1)
  4. Version of Record published: August 7, 2020 (version 2)

Copyright

© 2020, Manzano Nieves 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. Gabriela Manzano Nieves
  2. Marilyn Bravo
  3. Saba Baskoylu
  4. Kevin G Bath
(2020)
Early life adversity decreases pre-adolescent fear expression by accelerating amygdala PV cell development
eLife 9:e55263.
https://doi.org/10.7554/eLife.55263

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