Nucleus accumbens dopamine tracks aversive stimulus duration and prediction but not value or prediction error.

There is active debate on the role of dopamine in processing aversive stimuli, where inferred roles range from no involvement at all, to signaling an aversive prediction error (APE). Here, we systematically investigate dopamine release in the nucleus accumbens core (NAC), which is closely linked to reward prediction errors, in rats exposed to white noise (WN, a versatile, underutilized, aversive stimulus) and its predictive cues. Both induced a negative dopamine ramp, followed by slow signal recovery upon stimulus cessation. In contrast to reward conditioning, this dopamine signal was unaffected by WN value, context valence, or probabilistic contingencies, and the WN dopamine response shifted only partially toward its predictive cue. However, unpredicted WN provoked slower post-stimulus signal recovery than predicted WN. Despite differing signal qualities, dopamine responses to simultaneous presentation of rewarding and aversive stimuli were additive. Together, our findings demonstrate that instead of an APE, NAC dopamine primarily tracks prediction and duration of aversive events.

A unidirectional but not uniform striatal landscape of dopamine signaling for motivational stimuli.

Dopamine signals in the striatum are critical for motivated behavior. However, their regional specificity and precise information content are actively debated. Dopaminergic projections to the striatum are topographically organized. Thus, we quantified dopamine release in response to motivational stimuli and associated predictive cues in six principal striatal regions of unrestrained, behaving rats. Absolute signal size and its modulation by stimulus value and by subjective state of the animal were interregionally heterogeneous on a medial to lateral gradient. In contrast, dopamine-concentration direction of change was homogeneous across all regions: appetitive stimuli increased and aversive stimuli decreased dopamine concentration. Although cues predictive of such motivational stimuli acquired the same influence over dopamine homogeneously across all regions, dopamine-mediated prediction-error signals were restricted to the ventromedial, limbic striatum. Together, our findings demonstrate a nuanced striatal landscape of unidirectional but not uniform dopamine signals, topographically encoding distinct aspects of motivational stimuli and their prediction.

Striatal dopamine signals are region specific and temporally stable across action-sequence habit formation.

Habits are automatic, inflexible behaviors that develop slowly with repeated performance. Striatal dopamine signaling instantiates this habit-formation process, presumably region specifically and via ventral-to-dorsal and medial-to-lateral signal shifts. Here, we quantify dopamine release in regions implicated in these presumed shifts (ventromedial striatum [VMS], dorsomedial striatum [DMS], and dorsolateral striatum [DLS]) in rats performing an action-sequence task and characterize habit development throughout a 10-week training. Surprisingly, all regions exhibited stable dopamine dynamics throughout habit development. VMS and DLS signals did not differ between habitual and non-habitual animals, but DMS dopamine release increased during action-sequence initiation and decreased during action-sequence completion in habitual rats, whereas non-habitual rats showed opposite effects. Consistently, optogenetic stimulation of DMS dopamine release accelerated habit formation. Thus, we demonstrate that dopamine signals do not shift regionally during habit formation and that dopamine in DMS, but not VMS or DLS, determines habit bias, attributing "habit functions" to a region previously associated exclusively with non-habitual behavior.