Interactive effects of early life adversity and adolescent basolateral amygdala activity on corticolimbic connectivity and behavior

Corticolimbic development is shaped by the environment and relies on coordinated neuronal activity. Prior work revealed that early life adversity (ELA) leads to hyperinnervation of basolateral amygdala (BLA) projections to the prefrontal cortex (PFC) beginning in early adolescence. Both ELA and corticolimbic hyperconnectivity are associated with anxiety-like behavior, however the underlying developmental processes driving these effects are largely unknown. Here we investigated interactive impacts of rearing environment and neuronal activity on behavior and corticolimbic connectivity in rats. We first found that BLA-PFC hyperinnervation was associated with enhanced BLA-evoked PFC local field potentials in adolescents exposed to maternal separation (MS) ELA. Since ELA reportedly increases activity in the early-developing BLA, we further examined whether reducing BLA activity during adolescence influences behavior or enduring PFC innervation. During early adolescence, MS animals displayed heightened exploratory behaviors in an open field. Differences between rearing groups were not present during acute inhibition of glutamatergic BLA neurons, as BLA inhibition resembled the effects of MS on adolescent exploratory behaviors. To examine longer-lasting impacts of adolescent BLA activity on PFC innervation, BLA-originating axonal boutons were quantified in the PFC during emerging adulthood after adolescent BLA inhibition. We expanded previous findings to show that MS causes enduring BLA-PFC hyperinnervation. Surprisingly, adolescent BLA inhibition itself increased BLA-PFC innervation in control animals, suggesting that hyperpolarization of output neurons during early adolescence may contribute to aberrant development of efferent projections. Taken together, our results indicate that ELA yields increased BLA-PFC innervation in adulthood that may involve enhanced inhibitory signaling within developing BLA circuitry.