Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior.
Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior.
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DOI：
10.1523/jneurosci.2246-11.2011
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发表时间：
2011-07-27
期刊：
影响因子：
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通讯作者：
de Lecea L
中科院分区：
文献类型：
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作者：
Adamantidis AR;Tsai HC;Boutrel B;Zhang F;Stuber GD;Budygin EA;Touriño C;Bonci A;Deisseroth K;de Lecea L
多巴胺能神经元的阶段性激活与奖励预测线索相关，并支持行为适应过程中的学习。虽然腹侧被盖区（VTA）多巴胺能神经元的非偶然激活足以进行被动行为条件反射，但仍不清楚相位多巴胺能信号是否真正加强。在这项研究中，我们首先将视紫红质通道蛋白2（ChR2）的表达靶向腹侧被盖区的多巴胺能神经元，并优化了光遗传学诱发的多巴胺瞬变。第二，我们发现，在自由活动的小鼠多巴胺能神经元的阶段性激活因果关系增强积极的加强行动，在寻找食物的操作性任务。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熄灭的觅食行为。这也证实了使用一个单一的会话逆转范例。总的来说，这些数据表明，多巴胺能神经元的激活促进奖励寻求和行为灵活性过程中的正强化的发展。
Phasic activation of dopaminergic neurons is associated with reward-predicting cues and supports learning during behavioral adaptation. While non-contingent 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 (ChR2) 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.