Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, United States
Camila Demaestri
Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, United States
Shayna Peterzell
Developmental Neuropsychobiology Laboratory, Department of Psychology, Northeastern University, Boston, United States
Marisa M Silveri
Neurodevelopmental Laboratory on Addictions and Mental Health, McLean Hospital, Belmont, United States; Department of Psychiatry, Harvard Medical School, Boston, United States
Xuezhu Cai
Center for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, United States
Praveen Kulkarni
Center for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, United States
Miles G Cunningham
Laboratory for Neural Reconstruction, Department of Psychiatry, McLean Hospital, Belmont, United States
Craig F Ferris
Center for Translational Neuroimaging, Department of Psychology, Northeastern University, Boston, United States
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.
