1. Developmental Biology
  2. Neuroscience

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

  1. Jennifer A Honeycutt  Is a corresponding author
  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  Is a corresponding author
  1. Northeastern University, United States
  2. McLean Hospital, United States
https://doi.org/10.7554/eLife.52651
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

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.

Reviewing Editor

  1. Alexander Shackman, University of Maryland, United States

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.

Metrics

  • 4,384
    Page views
  • 519
    Downloads
  • 46
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Developmental Biology

    Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human

    Simon Schneider, Andjela Kovacevic ... Hubert Schorle
    Research Article

    Cylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (Cylc1/CYLC1) and the autosomal Cylicin 2 (Cylc2/CYLC2) genes, have been identified. Cylicins are cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While Cylicins have been localized in the acrosomal region of round spermatids, they resemble a major component of the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. However, the role of Cylicins during spermiogenesis has not yet been investigated. Here, we applied CRISPR/Cas9-mediated gene editing in zygotes to establish Cylc1- and Cylc2-deficient mouse lines as a model to study the function of these proteins. Cylc1 deficiency resulted in male subfertility, whereas Cylc2-/-, Cylc1-/yCylc2+/-, and Cylc1-/yCylc2-/- males were infertile. Phenotypical characterization revealed that loss of Cylicins prevents proper calyx assembly during spermiogenesis. This results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, and severe structural malformations, ultimately resulting in impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant in CYLC1 and a heterozygous variant in CYLC2, displaying morphological abnormalities of the sperm including the absence of the acrosome. Thus, our study highlights the relevance and importance of Cylicins for spermiogenic remodeling and male fertility in human and mouse, and provides the basis for further studies on unraveling the complex molecular interactions between perinuclear theca proteins required during spermiogenesis.

    1. Developmental Biology
    2. Stem Cells and Regenerative Medicine

    Microstructural differences in the osteochondral unit of terrestrial and aquatic mammals

    Irina AD Mancini, Riccardo Levato ... Jos Malda
    Research Article

    During evolution, animals have returned from land to water, adapting with morphological modifications to life in an aquatic environment. We compared the osteochondral units of the humeral head of marine and terrestrial mammals across species spanning a wide range of body weights, focusing on microstructural organization and biomechanical performance. Aquatic mammals feature cartilage with essentially random collagen fiber configuration, lacking the depth-dependent, arcade-like organization characteristic of terrestrial mammalian species. They have a less stiff articular cartilage at equilibrium with a significantly lower peak modulus, and at the osteochondral interface do not have a calcified cartilage layer, displaying only a thin, highly porous subchondral bone plate. This totally different constitution of the osteochondral unit in aquatic mammals reflects that accommodation of loading is the primordial function of the osteochondral unit. Recognizing the crucial importance of the microarchitecture-function relationship is pivotal for understanding articular biology and, hence, for the development of durable functional regenerative approaches for treatment of joint damage, which are thus far lacking.

    1. Cell Biology
    2. Developmental Biology

    Specific sensory neurons and insulin-like peptides modulate food type-dependent oogenesis and fertilization in Caenorhabditis elegans

    Shashwat Mishra, Mohamed Dabaja ... Joy Alcedo
    Research Article Updated

    An animal’s responses to environmental cues are critical for its reproductive program. Thus, a mechanism that allows the animal to sense and adjust to its environment should make for a more efficient reproductive physiology. Here, we demonstrate that in Caenorhabditis elegans specific sensory neurons influence onset of oogenesis through insulin signaling in response to food-derived cues. The chemosensory neurons ASJ modulate oogenesis onset through the insulin-like peptide (ILP) INS-6. In contrast, other sensory neurons, the olfactory neurons AWA, regulate food type-dependent differences in C. elegans fertilization rates, but not onset of oogenesis. AWA modulates fertilization rates at least partly in parallel to insulin receptor signaling, since the insulin receptor DAF-2 regulates fertilization independently of food type, which requires ILPs other than INS-6. Together our findings suggest that optimal reproduction requires the integration of diverse food-derived inputs through multiple neuronal signals acting on the C. elegans germline.