EFFECTS OF TSC2 KNOCK-DOWN IN JUVENILE AMYGDALA ON AMYGDALA AND PREFRONTAL CORTEX ACTIVITY IN ADOLESCENT RATS

Several anxiety-related disorders are associated with amygdala dysfunction during early periods of postnatal development, and adolescence is a particularly vulnerable emotional period. The mTOR signaling pathway has been proposed as a molecular regulator of emotional memories and could thus constitute a mechanistic source of the emergence of anxiety symptoms in these disorders. Given that the basolateral amygdala (BLA) matures earlier than the prefrontal cortex (PFC), both crucial to fear-related processes, we hypothesize that amygdala mTOR dysfunction during infancy can initiate a cascade of aberrant signaling processes, disrupting the normal development of the BLA – PFC fear circuit. Our aim is to determine the effects of mTOR over-activation in the BLA during infancy on BLA and PFC functionality and the emergence of behavioral alterations during adolescence. Rat pups (PN6-PN8) received bilateral BLA injections of either a control lentivirus or a lentivirus producing a partial knock-down of the Tsc2 gene (Tsc2-kd), resulting in hyperactivation of the mTOR signaling pathway, possibly altering BLA excitability. At adolescence, ex vivo electrophysiology investigated changes in BLA and PFC neural properties induced by Tsc2-kd. Our results show progressive changes in excitability of BLA pyramidal neurons throughout adolescence, associated with changes in firing properties of PFC neurons in late adolescence. Thus, changes observed in the PFC may have resulted from the gradual adaptation of BLA neurons to mTOR hyperactivation, attesting network malleability. fMRI and behavioral experiments are under way to assess BLA-PFC network connectivity in vivo, and their associated changes in anxiety-related behavior during adolescence. Funding: GS-LSH, FRC