Sex-dependent effects of early life stress on reinforcement learning and limbic cortico-striatal functional connectivity

• DOI: 10.1016/j.ynstr.2022.100507
• Publication Date: 2022-12-05T18:41:19Z
• Authors: Katharina Zühlsdorff; Laura López-Cruz; Ethan G. Dutcher; Jolyon A. Jones; Claudia Pama; Stephen Sawiak; Shahid Khan; Amy L. Milton; Trevor W. Robbins; Edward T. Bullmore; Jeffrey W. Dalley
• Keywords: Basolateral amygdala; Stressor; Dorsolateral prefrontal cortex

Major depressive disorder (MDD) is a stress-related condition hypothesized to involve aberrant reinforcement learning (RL) with positive and negative stimuli. The present study investigated whether repeated early maternal separation (REMS) stress, procedure widely recognized cause depression-like behaviour, affects how subjects learn from feedback. REMS was implemented by separating male female rats their dam for 6 h each day post-natal 5-19. Control rat offspring were left undisturbed during this period. Rats tested as adults behavioral flexibility feedback sensitivity on probabilistic reversal task. A computational approach based RL theory used derive latent variables related reward flexibility. To assess underlying brain substrates, seed-based functional MRI connectivity analysis applied both before after an additional adulthood stressor in control rats. Female but not exposed stress showed increased response 'stickiness' (repeated responses regardless of outcome). Following reduced the basolateral amygdala (BLA) dorsolateral striatum (DLS), cingulate cortex (Cg), anterior insula (AI) observed females. By contrast, second impaired (i.e., non-reward) BLA DLS AI compared maternally separated males. unaffected. fMRI data further revealed that between mOFC other prefrontal cortical subcortical structures positively correlated 'stickiness'. These findings reveal differences females males respond life adversity subsequent stress. effects may be mediated divergence resting-state fronto-striatal regions.