Aberrant cortical projections to amygdala GABAergic neurons contribute to developmental circuit dysfunction following early life stress

Early life stress (ELS) results in enduring dysfunction of the corticolimbic circuitry, underlying emotional and social behavior. However, the neurobiological mecha-nisms involved remain elusive. Here, we have combined viral tracing and electro-physiological techniques to study the effects of maternal separation (MS) on fron-tolimbic connectivity and function in young (P14-21) rats. We report that aberrant prefrontal inputs to basolateral amygdala (BLA) GABAergic interneurons tran-siently increase the strength of feed-forward inhibition in the BLA, which raises LTP induction threshold in MS treated male rats. The enhanced GABAergic activ-ity after MS exposure associates with lower functional synchronization within prefrontal-amygdala networks in vivo. Intriguingly, no differences in these pa-rameters 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 func-tional changes in the prefrontal-amygdaloid circuitry that predispose to neuro-psychiatric conditions later on in life.

Automated summary

Early life stress leads to long-term dysfunction in the corticolimbic circuitry, affecting emotional and social behavior. The underlying neurobiological mechanisms are still not well understood.