Dorsal tegmental dopamine neurons gate associative learning of fear

Functional neuroanatomy of Pavlovian fear has identified neuronal circuits and synapses associating conditioned stimuli with aversive events. Hebbian plasticity within these networks requires additional reinforcement to store particularly salient experiences into long-term memory. Here, we have identified a circuit reciprocally connecting the ventral periaqueductal grey (vPAG)/dorsal raphe (DR) region and the central amygdala (CE) that gates fear learning. We found that vPAG/DR dopaminergic (vPdRD) neurons encode a positive prediction error in response to unpredicted shocks, and may reshape intra-amygdala connectivity via a dopamine-dependent form of long-term potentiation (LTP). Negative feedback from the CE to vPdRD neurons might limit reinforcement to events that have not been predicted. These findings add a new module to the midbrain DA circuit architecture underlying associative reinforcement learning and identify vPdRD neurons as critical component of Pavlovian fear conditioning. We propose that dysregulation of vPdRD neuronal activity may contribute to fear-related psychiatric disorders.