Physiological state gates acquisition and expression of mesolimbic reward prediction signals

Associating environmental cues with their outcomes occurs through multiple strategies relying on different neural substrates. Unpredicted reward evokes dopamine release, which also develops to predictive cues, suggesting that predictive dopamine signals arise only after extensive pairings of cues with appetitive outcomes. However, recent work suggests that dopamine may also contribute to model-based learning, which does not require that cues and their appetitive outcomes be experienced in tandem. Taking advantage of the appetitive value of a hypertonic sodium solution, which radically and reversibly changes with physiological state, we show that dopamine differentially encodes hypertonic NaCl depending on sodium balance independent of prior experience. Conversely, dopamine only encoded a NaCl cue after extensive, state-dependent experience, firmly supporting dopamine’s role in experience-dependent learning