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.
- Shayna Peterzell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Alexander Shackman, University of Maryland, United States
© 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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