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

Brenhouse, Heather, Northeastern University, https://orcid.org/0000-0001-7591-4964

Honeycutt, Jennifer, Northeastern University

Demaestri, Camila, Northeastern University

Peterzell, Shayna, Northeastern University

Silveri, Marisa, McLean Hospital

Cai, Xuezhu, Northeastern University

Kulkarni, Praveen, Northeastern University

Ferris, Craig F, Northeastern University

Honeycutt, Jennifer A, Northeastern University, https://orcid.org/0000-0002-4879-0203

Cunningham, Miles G, McLean Hospital

Brenhouse, Heather C, Northeastern University, https://orcid.org/0000-0001-7591-4964

h.brenhouse@neu.edu, j.honeycutt@neu.edu, demaestri.c@husky.neu.edu, peterzell.s@husky.neu.edu, msilveri@mclean.harvard.edu, cai.xu@husky.neu.edu, P.Kulkarni@northeastern.edu, c.ferris@neu.edu

Publication date: May 4, 2020

Publisher: Dryad

https://doi.org/10.5061/dryad.jdfn2z371

Citation

Brenhouse, Heather et al. (2020), Altered corticolimbic connectivity reveals sex-specific adolescent outcomes in a rat model of early life adversity, Dryad, Dataset, https://doi.org/10.5061/dryad.jdfn2z371

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.

Funding

National Institute of Mental Health, Award: 1R01MH107556-01