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

Abstract

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.

Sex differences in behavioral responding and dopamine release during Pavlovian learning

“…For example, cue-evoked dopamine release conveys differences in the reward rate after extensive training (Fonzi et al, 2017). However, cue-evoked dopamine release does not signal differences in reward rate during early Pavlovian training sessions (Stelly et al, 2021). Our current results extend on these findings and demonstrate that cue-evoked dopamine release does not signal differences in reward size during early training sessions.…”

“…1A). Conditioned responding was quantified as the change in the rate of head entries during the 5 s CS relative to the rate of head entries during the 5 s preceding the CS (Fonzi et al, 2017;Stelly et al, 2020;Stelly et al, 2021). Rats increased conditioned responding across sessions, with no difference between Small and Large Reward cues (three-way mixed-effects analysis; session effect: F(2.26, 24.86) = 14.01, p < 0.0001; reward size effect: F(1, 11) = 0.03, p = 0.86; n = 13 rats, Fig.…”

“…The CS-evoked dopamine response was quantified as the average dopamine response during the 5 s CS relative to the 5 s prior to the CS delivery (Fonzi et al, 2017;Stelly et al, 2021). The US-evoked dopamine response was quantified as the average dopamine response during three 3 s time windows (Early: 0-3 s; Mid: 3-6 s; Late: 6-9 s) following the reward delivery, relative to the 0.5 s preceding the reward delivery.…”

“…Each session contained 25 Small Reward trials and 25 Large reward trials delivered in a pseudorandom order, with a 45 ± 5 s ITI between all trials. Conditioned responding was quantified as the change in the rate of head entries during the 5 s CS relative to the 5 s preceding the CS delivery (Fonzi et al, 2017;Stelly et al, 2021). We also quantified the latency to initiate a head entry during the CS.…”

Mesolimbic dopamine adapts the rate of learning from action

“…Such flexibility could support exploration of the policy space when appropriate (as in the naive conditions studied here), while promoting value learning in the conditions where it has been studied predominantly -in well-trained animals deciding between discrete options in the environment. Value effects following higher power, longer simulations may depend on specific receptor recruitment within a circuit 74 , and/or recruitment of a wider population of DA circuits, as a spectrum of DA function and signaling has been demonstrated across striatal subregions 15,18,69,[75][76][77][78] . Future experiments exploring a putative threshold for phasic DA-driven value learning may yield insight into both adaptive and maladaptive functions of dopamine-recipient circuits in the forebrain.…”