The basal ganglia–habenula circuitry in reward processing

 描述（由申请人提供）：基底神经节-缰核回路在奖励处理这个项目的总体目标是调查奖励处理的基本大脑机制。最近的研究表明，外侧缰核（LHb）提供的价信号中脑多巴胺区。然而，部分由于在监测和操纵LHb回路中的活动方面的挑战，这种回路在更复杂的行为中的作用仍然难以捉摸。特别是，LHb神经元如何获得价信号，以及这些信号是否以及如何用于指导行为，仍然是尚未解决的问题。弥合这些差距具有重要的临床意义，因为LHb功能障碍与抑郁症的发病机制有关，抑郁症是一种主要的精神疾病，其中奖励处理缺陷是其标志。 在拟议的研究中，我们计划通过研究基底神经节外侧缰回路中功能不同的神经元群如何协调和参与奖励处理来解决这些问题，从而影响行为。为此，我们设计了一种综合策略，将分子遗传学工具与电生理学，成像，光遗传学，化学遗传学和行为技术相结合。这项研究计划的结果将提供新的洞察突触，细胞和电路机制，基底神经节外侧缰电路有助于奖励相关的过程。

 DESCRIPTION (provided by applicant): The basal ganglia-habenula circuitry in reward processing the overall goal of this project is to investigate the basic brain mechanisms underlying reward processing. Recent studies demonstrate that the lateral habenula (LHb) provides valence signals to the midbrain dopamine areas. However, in part owing to the challenges in monitoring and manipulating activities in the LHb circuitry, the roles of this circuiry in more complex behaviors still remain elusive. In particular, how LHb neurons acquire the valence signals, and whether and how these signals are used to guide behavior, are questions that remain unresolved. Bridging these gaps is of great clinical significance, because LHb dysfunction is implicated in the pathogenesis of depression, a major psychiatric disorder in which deficit in reward processing is the hallmark. In the proposed study, we plan to approach these questions by investigating how functionally distinct groups of neurons in the basal ganglia-lateral habenula circuitry coordinate and participate in reward processing, thereby influencing behavior. For this purpose we have devised an integrated strategy that combines molecular genetic tools together with electrophysiological, imaging, optogenetic, chemogenetic, and behavioral techniques. Findings from this research program will provide novel insight into the synaptic, cellular, and circuit mechanisms by which the basal ganglia-lateral habenula circuitry contributes to reward-related processes.