EARLY LIFE STRESS IS ASSOCIATED WITH PRECOCIOUS AMYGDALA DEVELOPMENT AND AN UNEXPECTED DIP IN THREAT-ASSOCIATED FREEZING

Kevin G. Bath, Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, RI, USA.

Early life stress (ELS) increases the lifetime risk for affective pathology in humans and animal models. The mechanisms underlying increased risk for later pathology are not well understood. Here, we investigate the effect of ELS on the development of cued and contextual threat-associated learning in a mouse model of ELS. Stress was induced through the use of a maternal bedding restriction paradigm from P4-P11. Development of threat associated learning and neural circuitry underlying these behaviors was assessed in separate cohorts of mice at P16, 21, 28, and 50 days of age. In the contextual fear learning paradigm, ELS was associated with a significant acceleration in the development of contextual fear suppression, an effect that was associated with precocious maturation of the hippocampus. Interestingly, for auditory cued fear, we observed what appeared to be a delay in development of tone-associated freezing, as ELS mice failed to show normal levels of freezing at postnatal day 21, compared with control reared mice. To understand the mechanisms underlying this observation, we tracked the effects of ELS on circuit development, and found asymmetries in the effect of ELS on the timing of cortical and basolateral amygdala (BLA) development (accelerated maturation of the BLA, but delays in PL connections to BLA). These data support the notion that ELS can significantly alter the timing of regional brain development, but may not do so uniformly across the brain.  Such effect have significant consequences for behavioral maturation, and the development of appropriate responding to environmental cues.