RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, Japan, 351-0198.
RIKEN Center for Brain Science, 2-1 Hirosawa, Wako-shi, Saitama, Japan, 351-0198.
Nat Commun. 2018 Jun 27;9(1):2483. doi: 10.1038/s41467-018-04784-7.
Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate so that they can be extinguished. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signaling when a better-than-expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions. We report that when an expected aversive outcome does not occur, activity in midbrain dopamine neurons is necessary to extinguish behavioral fear responses and engage molecular signaling events in extinction learning circuits. Furthermore, a specific dopamine projection to the nucleus accumbens medial shell is partially responsible for this effect. In contrast, a separate dopamine projection to the medial prefrontal cortex opposes extinction learning. This demonstrates a novel function for the canonical VTA-dopamine reward system and reveals opposing behavioral roles for different dopamine neuron projections in fear extinction learning.
克服厌恶情绪记忆需要能够检测到恐惧反应不再合适的神经系统，以便对其进行消除。中脑腹侧被盖区（VTA）多巴胺系统已被牵涉到奖励中，更广泛地被牵涉到指示何时出现好于预期的结果。这表明它可能对指导恐惧向安全过渡很重要。我们报告说，当预期的不愉快结果没有发生时，中脑多巴胺神经元的活动对于消除行为恐惧反应和参与消退学习回路中的分子信号事件是必要的。此外，多巴胺对伏隔核内侧壳的特定投射部分负责这种效果。相比之下，对内侧前额叶皮层的单独多巴胺投射则与消退学习相反。这证明了经典 VTA-多巴胺奖励系统的新功能，并揭示了不同多巴胺神经元投射在恐惧消退学习中的相反行为作用。
