Transient developmental increase in cortical projections to amygdala GABAergic neurons contribute to circuit dysfunction following early life stress

Abstract

Early life stress (ELS) results in enduring dysfunction of the cortico-limbic circuitry, underlying emotional and social behavior. However, the neurobiological mechanisms by which ELS affects development of the circuitry remain elusive. Here, we have combined viral tracing and electrophysiological techniques to study the effects of maternal separation (MS) on fronto-limbic connectivity and function in young (P14-21) rats. We report that aberrant prefrontal (mPFC) inputs to basolateral amygdala (BLA) GABAergic interneurons transiently increase the strength of feedforward inhibition in the BLA, which raises LTP induction threshold in MS treated male rats. The enhanced GABAergic activity after MS exposure associates with lower functional synchronization within prefrontal-amygdala networks in vivo. Intriguingly, no differences in these parameters were detected in females, which were also resistant to MS dependent changes in anxiety-like behaviors. Impaired plasticity and synchronization during the sensitive period of circuit refinement may contribute to long-lasting functional changes in the prefrontal-amygdaloid circuitry that predispose to neuropsychiatric conditions later on in life.