Chemogenetic activation of mesoaccumbal Gamma-Aminobutyric Acid projections selectively tunes responses to predictive cues when reward value is abruptly decreased

Abstract Background Mesolimbic circuits regulate the attribution of motivational significance to incentive cues that predict reward, yet this network also plays a key role in adapting reward-seeking behavior when the contingencies linked to a cue unexpectedly change. Here we asked whether mesoaccumbal gamma-aminobutyric acid (GABA) projections enhance adaptive responding to incentive cues of abruptly altered reward value, and whether these effects were distinct from global activation of all ventral tegmental area (VTA) GABA circuits. Methods We used a viral targeting system to chemogenetically activate mesoaccumbal GABA projections in male rats during a novel cue-dependent operant Value Shifting (VS) task, in which the volume of a sucrose reward associated with a predictive cue is suddenly altered, from the beginning and throughout the session. We compared the results with global activation of VTA GABA neurons, which will activate local inhibitory circuits and long loop projections. Results We found that activation of mesoaccumbal GABA projections decreases responding to incentive cues associated with smaller-than-expected rewards. This tuning of behavioral responses was specific to cues associated with smaller-than-expected rewards, but did not impact measures related to consuming the reward. In marked contrast, activating all VTA(GABA) neurons resulted in a uniform decrease in responding to incentive cues irrespective of changes in the size of the reward. Conclusions Targeted activation of mesoaccumbal GABA neurons facilitate adaptation in reward-seeking behaviors. This suggests that these projections may play a very specific role in associative learning processes.