Medial accumbens shell spiny projection neurons encode relative reward preference

Medial nucleus accumbens shell (mNAcSh) is a critical brain region for driving motivated behaviors. Despite this well-established role, the underlying reward processing of individual neurons, circuits and cell-types within mNAcSh remains largely unknown. Here, we leverage deep brain 2-photon calcium imaging through endoscopic lenses to record mNAcSh spiny projection neuron (SPN) ensemble responses to rewards of different preference and to reward-predictive cues across cue-reward learning. Reward responses were found to be heterogeneous and particularly differentiated based on reward preference and cell type. A large subpopulation of reward-excited enkephalinergic SPNs were found to be specifically recruited during consumption of unpreferred rewards. A major enkephalinergic efferent projection from mNAcSh to ventral pallidum (VP) was also found to be recruited to unpreferred rewards and to causally drive low positive reward preference. Enkephalin and dynorphinergic SPNs in mNAcSh distinctly represent rewards of different preference and propagate distinct signals through efferent projections to drive consummatory behavior.