Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.
J Neurosci. 2011 Jul 27;31(30):10829-35. doi: 10.1523/JNEUROSCI.2246-11.2011.
Phasic activation of dopaminergic neurons is associated with reward-predicting cues and supports learning during behavioral adaptation. While noncontingent activation of dopaminergic neurons in the ventral tegmental are (VTA) is sufficient for passive behavioral conditioning, it remains unknown whether the phasic dopaminergic signal is truly reinforcing. In this study, we first targeted the expression of channelrhodopsin-2 to dopaminergic neurons of the VTA and optimized optogenetically evoked dopamine transients. Second, we showed that phasic activation of dopaminergic neurons in freely moving mice causally enhances positive reinforcing actions in a food-seeking operant task. Interestingly, such effect was not found in the absence of food reward. We further found that phasic activation of dopaminergic neurons is sufficient to reactivate previously extinguished food-seeking behavior in the absence of external cues. This was also confirmed using a single-session reversal paradigm. Collectively, these data suggest that activation of dopaminergic neurons facilitates the development of positive reinforcement during reward-seeking and behavioral flexibility.
多巴胺能神经元的阶段性激活与奖励预测线索有关，并支持行为适应过程中的学习。虽然腹侧被盖区（VTA）中的多巴胺神经元的非条件激活足以进行被动行为调节，但仍不清楚阶段性多巴胺信号是否真的具有强化作用。在这项研究中，我们首先将通道型视蛋白-2的表达靶向到 VTA 的多巴胺能神经元，并优化了光遗传学引发的多巴胺瞬变。其次，我们表明，在自由活动的小鼠中，多巴胺能神经元的阶段性激活会在食物寻求操作性任务中因果性地增强正强化作用。有趣的是，在没有食物奖励的情况下，没有发现这种效果。我们进一步发现，多巴胺能神经元的阶段性激活足以在没有外部线索的情况下重新激活先前被消除的食物寻求行为。这一点也通过单次反转范式得到了证实。总的来说，这些数据表明，多巴胺能神经元的激活有助于在寻求奖励和行为灵活性过程中增强正强化作用。
