Nucleus accumbens neurons dynamically encode positive and aversive associative learning

Abstract To survive, individuals must learn to associate cues in the environment with emotionally relevant outcomes. This association is partially mediated by the nucleus accumbens (NAc), a key brain region of the reward circuit that is mainly composed by GABAergic medium spiny neurons (MSNs), that express either dopamine receptor D1 or D2. Recent studies showed that both populations can drive reward and aversion, however, the activity of these neurons during appetitive and aversive Pavlovian conditioning remains to be determined. Here, we investigated the relevance of D1- and D2-neurons in Pavlovian associations, by measuring calcium transients with fiber photometry during appetitive and aversive Pavlovian tasks. Sucrose was used as a positive unconditioned stimulus (US) and foot shock was used as a negative US. We show that during appetitive Pavlovian conditioning, D1- and D2-neurons exhibit a general decrease in activity in response to CS and to US across learning, with dynamic, and partially overlapping, activity responses to CS and US. During the aversive Pavlovian conditioning, D1- and D2-neurons showed an increase in the activity in response to the CS and to the US (shock). Our data supports a synchronous role for D1- and D2-neurons in appetitive and aversion processing.