Nucleus accumbens dopamine encodes the trace period during appetitive Pavlovian conditioning

Abstract

Pavlovian conditioning tasks have been used to identify the neural systems involved with learning cue-outcome relationships. In delay conditioning, the conditioned stimulus (CS) overlaps or co-terminates with the delivery of the unconditioned stimulus (US). Prior studies demonstrate that dopamine in the nucleus accumbens (NAc) regulates behavioral responding during delay conditioning. Furthermore, the dopamine response to the CS reflects the relative value of the upcoming reward in these tasks. In contrast to delay conditioning, trace conditioning involves a 'trace' period separating the end of the CS and the US delivery. While dopamine has been implicated in trace conditioning, no studies have examined how NAc dopamine responds to reward-related stimuli in these tasks. Here, we developed a within-subject trace conditioning task where distinct CSs signaled either a short trace period (5s) or a long trace period (55s) prior to food reward delivery. Male rats exhibited greater conditioned responding and a faster response latency to the Short Trace CS relative to the Long Trace CS. Voltammetry recordings in the NAc found that the CS-evoked dopamine response increased on Short Trace trials but decreased on Long Trace trials. Conversely, US-evoked dopamine responses were greater on Long Trace trials relative to Short Trace trials. The CS dopamine response correlated with the response latency and not with conditioned responding. Furthermore, the relationship between CS dopamine and latency was best explained by an exponential function. Our results collectively illustrate that the trace period is encoded by the bidirectional NAc dopamine response to the CS during Pavlovian conditioning.

Significance statement: Learning to associate a cue with given outcome is a fundamental process underlying reward seeking behavior. Striatal dopamine is important for associating cues with rewards during Pavlovian conditioning. However, it is unclear how the dopamine system responds to cues during trace conditioning when there is temporal gap between the cue and reward. Here, we performed voltammetry recordings of striatal dopamine levels in male rats during trace conditioning. We find that cue-evoked dopamine signals encode the trace period and is related to the response latency. While prior reports find dopamine neurons signal the relative reward value by increases in dopamine levels, we demonstrate that the dopamine response to reward-predictive cues can signal the reward value through bidirectional changes in dopamine transmission.