Altered corticolimbic connectivity reveals sex-specific adolescent outcomes in a rat model of early life adversity

Abstract

Exposure to early-life adversity (ELA) increases the risk for psychopathologies associated with amygdala-prefrontal cortex (PFC) circuits. While sex differences in vulnerability have been identified with a clear need for individualized intervention strategies, the neurobiological substrates of ELA-attributable differences remain unknown due to a paucity of translational investigations taking both development and sex into account. Male and female rats exposed to maternal separation ELA were analyzed with anterograde tracing from basolateral amygdala (BLA) to PFC to identify sex-specific innervation trajectories through juvenility (PD28) and adolescence (PD38;PD48). Resting-state functional connectivity (rsFC) was assessed longitudinally (PD28;PD48) in a separate cohort. All measures were related to anxiety-like behavior. ELA-exposed rats showed precocial maturation of BLA-PFC innervation, with females affected earlier than males. ELA also disrupted maturation of female rsFC, with enduring relationships between rsFC and anxiety-like behavior. This study is the first providing both anatomical and functional evidence for sex- and experience-dependent corticolimbic development.

Data availability

All data generated for Figures 1, 2, 3, 4, and S4 are provided as source data files. Data generated for Figures 5 and 6 will be made available once an ongoing additional analysis is completed for another research report.Data deposited to Dryad, doi:10.5061/dryad.jdfn2z371

The following data sets were generated

Article and author information

Author details

  1. Jennifer A Honeycutt

    Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, United States
    For correspondence
    j.honeycutt@northeastern.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4879-0203
  2. Camila Demaestri

    Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, United States
    Competing interests
    No competing interests declared.
  3. Shayna Peterzell

    Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, United States
    Competing interests
    No competing interests declared.
  4. Marisa M Silveri

    Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital, Belmont, United States
    Competing interests
    No competing interests declared.
  5. Xuezhu Cai

    Center for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, United States
    Competing interests
    No competing interests declared.
  6. Praveen Kulkarni

    Center for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, United States
    Competing interests
    No competing interests declared.
  7. Miles G Cunningham

    Laboratory for Neural Reconstruction, Department of Psychiatry, McLean Hospital, Belmont, United States
    Competing interests
    No competing interests declared.
  8. Craig F Ferris

    Center for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, United States
    Competing interests
    Craig F Ferris, has a financial interest in Animal Imaging Research, the company that makes the rat imaging system.
  9. Heather C Brenhouse

    Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, United States
    For correspondence
    h.brenhouse@neu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7591-4964

Funding

National Institute of Mental Health (1R01MH107556-01)

  • Shayna Peterzell

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

Reviewing Editor

  1. Alexander Shackman, University of Maryland, United States

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 (#19-0313R) of Northeastern University. The protocol was approved by the IACUC of Northeastern University (Animal Welfare #: D16-00095). All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Version history

  1. Received: October 11, 2019
  2. Accepted: January 17, 2020
  3. Accepted Manuscript published: January 20, 2020 (version 1)
  4. Version of Record published: February 10, 2020 (version 2)

Copyright

© 2020, Honeycutt 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. Jennifer A Honeycutt
  2. Camila Demaestri
  3. Shayna Peterzell
  4. Marisa M Silveri
  5. Xuezhu Cai
  6. Praveen Kulkarni
  7. Miles G Cunningham
  8. Craig F Ferris
  9. Heather C Brenhouse
(2020)
Altered corticolimbic connectivity reveals sex-specific adolescent outcomes in a rat model of early life adversity
eLife 9:e52651.
https://doi.org/10.7554/eLife.52651

Share this article

https://doi.org/10.7554/eLife.52651

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