NMDA receptor-dependent plasticity in the nucleus accumbens connects reward-predictive cues to approach responses

Learning associations between environmental cues and rewards is a fundamental adaptive function. Via such learning, reward-predictive cues come to activate approach to locations where reward is available. The nucleus accumbens (NAc) is essential for cued approach behavior in trained subjects, and cue-evoked excitations in NAc neurons are critical for the expression of this behavior. Excitatory synapses within the NAc undergo synaptic plasticity that presumably contributes to cued approach acquisition, but a direct link between synaptic plasticity within the NAc and the development of cue-evoked neural activity during learning has not been established. Here we show that, with repeated cue-reward pairings, cue-evoked excitations in the NAc emerge and grow in the trials prior to the detectable expression of cued approach behavior. We demonstrate that the growth of these signals requires NMDA receptor-dependent plasticity within the NAc, revealing a neural mechanism by which the NAc participates in learning of conditioned reward-seeking behaviors.