UCSF

Basolateral amygdala (BLA) neurons are excited by conditioned cues after appetitive or aversive Pavlovian conditioning, and these neuronal excitations are considered to be a substrate for cue- outcome associative learning. However, an equal or greater number of BLA neurons can be inhibited by conditioned cues, and the role and mechanism of this inhibitory signal are not understood. Here we show that 77% of BLA neurons demonstrate long-lasting inhibition during a reward-predictive cue that is positively correlated with both learning and extinction of reward seeking. Optogenetic activation of BLA projection neurons during cue presentation impaired conditioned behavior, consistent with cue-evoked inhibition in BLA causally contributing to this behavior. Pharmacological inactivation of the orbitofrontal cortex (OFC) and optogenetic inactivation of OFC axon terminals in BLA also reduced conditioned behavior, with pharmacological inactivation of OFC additionally diminishing BLA cue-evoked inhibitions. Together, these data reveal a new role for BLA neuronal inhibitions in conditioned behavior, and suggest that this signal is mediated in part by OFC axon projections to BLA, which may activate local interneurons.