Impacts of Early Life Stress on Adult Emotive Behavior and the PFC-Amygdala Circuit

Abstract

Fear responses in mammals are ancient and adaptive responses. Specialized neural systems have evolved to support adaptive responses, and these have critical developmental time points. Disrupting development of these systems with environmental stress impacts mood and conduct, and as adults, stressed individuals demonstrate depressive or anxiety -like behavior. This project investigates impacts of early life stress (ELS) on behavior and the synaptic physiology of the basolateral amygdala and prelimbic (PL) and infralimbic (IL) areas of the prefrontal cortex (PFC) in rodents. C57/BL6 male and female mouse pups were subjected to maternal separation (with concurrent maternal stress) and isolation during the critical neurodevelopmental period of postnatal day 10 to 17 (PND10-17) and then housed normally until adulthood (ELS group). Another cohort of male and female mice grew under normal conditions but underwent forced swim stress in adulthood (Adult stress group). Both groups of animals plus a home-cage control group (male and female) were assessed with a battery of tests to measure depressive and anxiety- like behaviors, and subsequently sacrificed for electrophysiological experiments. Behavioral analyses show ELS mice exhibited phenotypes consistent with depressive and anxiety- like behaviors that appear to match those observed in adult stressed mice. Analysis for sex differences revealed performance-specific differences between groups. Electrophysiological analyses indicate ELS mice show increased postsynaptic excitability in the basolateral amygdala and increased presynaptic drive in PL and IL PFC compared with control animals, as well as sex differences. Our findings indicate that ELS causes behavioral disruptions and dysregulation of synaptic function in amygdala and PFC that lasts into adulthood.