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.

The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of pre-frontal cue-reward associations are unresolved. We trained headfixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding, including coding of trial-by-trial reward history, in all regions we sampled. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.

The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of neural cue-reward associations are unresolved. We trained headfixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues and licks were most common in olfactory and motor cortex, respectively. By classifying cue-encoding neurons according to their responses to the six odor cues, we unexpectedly found value coding, including coding of trial-by-trial reward history, in all regions we sampled. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.

The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of pre-frontal cue-reward associations are unresolved. We trained headfixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding, including coding of trial-by-trial reward history, in all regions we sampled. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.

The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of prefrontal cue-reward associations are unresolved. We trained head-fixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in the olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding in all regions we sampled, with some enrichment in the prefrontal cortex. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.