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 GABA (gamma-aminobutyric acid) 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 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 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 ventral tegmental area 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 ventral tegmental area 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 facilitates adaptation in reward-seeking behaviors. This suggests that these projections may play a very specific role in associative learning processes.

中文翻译：

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当奖励值突然降低时，mesoaccumbal γ-氨基丁酸投射的化学遗传学激活选择性地调整对预测线索的反应

背景 中脑边缘回路调节动机意义对预测奖励的激励线索的归因，但当与线索相关的意外事件发生意外变化时，该网络在适应寻求奖励的行为中也起着关键作用。在这里，我们询问 mesoaccumbal GABA（γ-氨基丁酸）预测是否增强了对突然改变的奖励值的激励线索的适应性反应，以及这些影响是否与所有腹侧被盖区 GABA 回路的全局激活不同。方法 我们使用病毒靶向系统在一项新的依赖于线索的操作性价值转移任务期间化学激活雄性大鼠中的 mesoaccumbal GABA 投射，其中与预测线索相关的蔗糖奖励量从开始和整个过程中突然改变会议。我们将结果与腹侧被盖区 GABA 神经元的全局激活进行了比较，这将激活局部抑制回路和长环投射。结果我们发现，对与小于预期的奖励相关的激励线索的响应，mesoaccumbal GABA 预测的激活会降低。这种行为反应的调整特定于与小于预期的奖励相关的线索，但不影响与消耗奖励相关的措施。与此形成鲜明对比的是，无论奖励大小如何变化，激活所有腹侧被盖区 GABA 神经元都会导致对激励线索的反应均匀减少。结论 中层 GABA 神经元的靶向激活促进了寻求奖励行为的适应。