Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Neuroscience Program, Stanford University, Stanford, CA 94305, USA.
Neuron. 2019 Jan 2;101(1):133-151.e7. doi: 10.1016/j.neuron.2018.11.005. Epub 2018 Nov 29.
Ventral tegmental area (VTA) dopamine (DA) neurons play a central role in mediating motivated behaviors, but the circuitry through which they signal positive and negative motivational stimuli is incompletely understood. Using in vivo fiber photometry, we simultaneously recorded activity in DA terminals in different nucleus accumbens (NAc) subnuclei during an aversive and reward conditioning task. We find that DA terminals in the ventral NAc medial shell (vNAcMed) are excited by unexpected aversive outcomes and to cues that predict them, whereas DA terminals in other NAc subregions are persistently depressed. Excitation to reward-predictive cues dominated in the NAc lateral shell and was largely absent in the vNAcMed. Moreover, we demonstrate that glutamatergic (VGLUT2-expressing) neurons in the lateral hypothalamus represent a key afferent input for providing information about aversive outcomes to vNAcMed-projecting DA neurons. Collectively, we reveal the distinct functional contributions of separate mesolimbic DA subsystems and their afferent pathways underlying motivated behaviors. VIDEO ABSTRACT.
腹侧被盖区（VTA）多巴胺（DA）神经元在介导动机行为方面起着核心作用，但它们传递正性和负性动机刺激的回路尚不完全清楚。使用在体光纤光度法，我们在厌恶和奖励条件作用任务期间同时记录了不同伏隔核（NAc）亚区 DA 末梢中的活动。我们发现，腹侧 NAc 内侧壳（vNAcMed）中的 DA 末梢被意外的厌恶结果和预测它们的线索所兴奋，而其他 NAc 亚区中的 DA 末梢则持续被抑制。在 NAc 外侧壳中，预测奖赏的线索引起的兴奋占主导地位，而在 vNAcMed 中则基本不存在。此外，我们证明外侧下丘脑中的谷氨酸能（表达 VGLUT2 的）神经元是向投射到 vNAcMed 的 DA 神经元提供有关厌恶结果信息的关键传入输入。总的来说，我们揭示了不同的中脑边缘 DA 子系统及其在动机行为中的传入通路的独特功能贡献。视频摘要。
