Pattern of dopamine signaling during aversive events predicts active avoidance learning.

Learning to avoid aversive outcomes is an adaptive strategy to limit one's future exposure to stressful events. However, there is considerable variance in active avoidance learning across a population. The mesolimbic dopamine system contributes to behaviors elicited by aversive stimuli, although it is unclear if the heterogeneity in active avoidance learning is explained by differences in dopamine transmission. Furthermore, it is not known how dopamine signals evolve throughout active avoidance learning. To address these questions, we performed voltammetry recordings of dopamine release in the ventral medial striatum throughout training on inescapable footshock and signaled active avoidance tasks. This approach revealed differences in the pattern of dopamine signaling during the aversive cue and the safety period that corresponded to subsequent task performance. Dopamine transmission throughout the footshock bout did not predict performance but rather was modulated by the prior stress exposure. Additionally, we demonstrate that dopamine encodes a safety prediction error signal, which illustrates that ventral medial striatal dopamine release conveys a learning signal during both appetitive and aversive conditions.

Critical periods when dopamine controls behavioral responding during Pavlovian learning.

RATIONALE: Learning the association between rewards and predictive cues is critical for appetitive behavioral responding. The mesolimbic dopamine system is thought to play an integral role in establishing these cue-reward associations. The dopamine response to cues can signal differences in reward value, though this emerges only after significant training. This suggests that the dopamine system may differentially regulate behavioral responding depending on the phase of training. OBJECTIVES: The purpose of this study was to determine whether antagonizing dopamine receptors elicited different effects on behavior depending on the phase of training or the type of Pavlovian task. METHODS: Separate groups of male rats were trained on Pavlovian tasks in which distinct audio cues signaled either differences in reward size or differences in reward rate. The dopamine receptor antagonist flupenthixol was systemically administered prior to either the first ten sessions of training (acquisition phase) or the second ten sessions of training (expression phase), and we monitored the effect of these manipulations for an additional ten training sessions. RESULTS: We identified acute effects of dopamine receptor antagonism on conditioned responding, the latency to respond, and post-reward head entries in both Pavlovian tasks. Interestingly, dopamine receptor antagonism during the expression phase produced persistent deficits in behavioral responding only in rats trained on the reward size Pavlovian task. CONCLUSIONS: Together, our results illustrate that dopamine's control over behavior in Pavlovian tasks depends upon one's prior training experience and the information signaled by the cues.

Dopamine release and its control over early Pavlovian learning differs between the NAc core and medial NAc shell.

Dopamine neurons respond to cues to reflect the value of associated outcomes. These cue-evoked dopamine responses can encode the relative rate of reward in rats with extensive Pavlovian training. Specifically, a cue that always follows the previous reward by a short delay (high reward rate) evokes a larger dopamine response in the nucleus accumbens (NAc) core relative to a distinct cue that always follows the prior reward by a long delay (low reward rate). However, it was unclear if these reward rate dopamine signals are evident during early Pavlovian training sessions and across NAc subregions. To address this, we performed fast-scan cyclic voltammetry recordings of dopamine levels to track the pattern of cue- and reward-evoked dopamine signals in the NAc core and medial NAc shell. We identified regional differences in the progression of cue-evoked dopamine signals across training. However, the dopamine response to cues did not reflect the reward rate in either the NAc core or the medial NAc shell during early training sessions. Pharmacological experiments found that dopamine-sensitive conditioned responding emerged in the NAc core before the medial NAc shell. Together, these findings illustrate regional differences in NAc dopamine release and its control over behavior during early Pavlovian learning.

Dopamine Encodes Retrospective Temporal Information in a Context-Independent Manner.

The dopamine system responds to reward-predictive cues to reflect a prospective estimation of reward value, although its role in encoding retrospective reward-related information is unclear. We report that cue-evoked dopamine release in the nucleus accumbens core encodes the time elapsed since the previous reward or rather the wait time. Specifically, a cue that always follows the preceding reward with a short wait time elicits a greater dopamine response relative to a distinct cue that always follows the preceding reward with a long wait time. Differences in the dopamine response between short wait and long wait cues were evident even when these cues were never experienced together within the same context. Conditioned responding updated accordingly with a change in cue-evoked dopamine release but was unrelated to a difference in the dopamine response between cues. Collectively, these findings illustrate that the cue-evoked dopamine response conveys a subjective estimation of the relative reward rate.