Graduate Program in Neuroscience, University of Washington, Seattle, WA, USA.
Department of Biological Structure, University of Washington, Seattle, WA, USA; University of Washington Center of Excellence in Neurobiology of Addiction, Pain, and Emotion (NAPE), Seattle, WA, USA.
Cell Rep. 2024 Sep 24;43(9):114668. doi: 10.1016/j.celrep.2024.114668. Epub 2024 Aug 27.
Ventral tegmental area (VTA) dopamine neurons regulate reward-related associative learning and reward-driven motivated behaviors, but how these processes are coordinated by distinct VTA neuronal subpopulations remains unresolved. Here, we compare the contribution of two primarily dopaminergic and largely non-overlapping VTA subpopulations, all VTA dopamine neurons and VTA GABAergic neurons of the mouse midbrain, to these processes. We find that the dopamine subpopulation that projects to the nucleus accumbens (NAc) core preferentially encodes reward-predictive cues and prediction errors. In contrast, the subpopulation that projects to the NAc shell preferentially encodes goal-directed actions and relative reward anticipation. VTA GABA neuron activity strongly contrasts VTA dopamine population activity and preferentially encodes reward outcome and retrieval. Electrophysiology, targeted optogenetics, and whole-brain input mapping reveal multiple convergent sources that contribute to the heterogeneity among VTA dopamine subpopulations that likely underlies their distinct encoding of reward-related associations and motivation that defines their functions in these contexts.
腹侧被盖区 (VTA) 多巴胺神经元调节与奖励相关的联想学习和奖励驱动的动机行为，但这些过程如何被不同的 VTA 神经元亚群协调仍未解决。在这里，我们比较了两个主要的多巴胺能和很大程度上不重叠的 VTA 亚群，即中脑 VTA 多巴胺神经元和 VTA GABA 神经元，对这些过程的贡献。我们发现，投射到伏隔核核心的多巴胺亚群优先编码奖励预测线索和预测误差。相比之下，投射到伏隔核壳的亚群优先编码目标导向的动作和相对奖励预期。VTA GABA 神经元的活动与 VTA 多巴胺群体的活动强烈对比，优先编码奖励结果和检索。电生理学、靶向光遗传学和全脑输入映射揭示了多个汇聚的来源，这些来源促成了 VTA 多巴胺亚群之间的异质性，这可能是它们对奖励相关关联和动机的不同编码的基础，从而定义了它们在这些情况下的功能。
