Sex hormone regulation of Lateral Habenula circuitry for reward and aversion encoding

项目摘要 这项提案旨在调查性激素对奖励和厌恶相关行为的影响， 侧缰（LHb）回路的映射。LHb是编码厌恶信息的重要中枢 和协调有动机的行为，对生存至关重要的行动。LHb依赖性电路的功能障碍 导致了一系列不同的无序行为，例如正负价的异常处理， 快感缺乏症、抑郁性精神病学和适应不良应激反应，仅举几例。虽然已知 动机行为是由循环性激素调节的，没有研究调查是否消极 电路调节器，特别是来自LHb的突起，促成了这种现象。此外，核 大脑中的激素受体尚未得到很好的表征，因此了解它们在LHb中的作用 奖励回路以及它们如何与循环激素相互作用，将为我们提供有关性驱动机制的见解。 激素对奖赏相关行为的影响。在这项建议中，通过利用最新的 技术来定义，操纵和监测神经活动，我计划测试特定的功能贡献 LHb投射神经元上的激素受体对奖赏和厌恶相关行为的影响。

Project Summary This proposal seeks to investigate sex hormone effects on reward and aversion-related behaviors through mapping of Lateral Habenula (LHb) circuits. The LHb is a central hub important for encoding aversive information and coordinating motivated behaviors, actions critical for survival. Dysfunction in LHb-dependent circuits contribute to a diverse set of disordered behaviors, such as aberrant processing of positive and negative valence, anhedonia, depressive symptomology, and maladaptive stress response, to name a few. While it is known that motivated behaviors are modulated by circulating sex hormones, no studies have investigated whether negative circuit regulators, specifically projections from the LHb, contribute to this phenomenon. Furthermore, nuclear hormone receptors in the brain have not been well characterized, therefore understanding their role within LHb reward circuits and how they interact with circulating hormones will provide insight into mechanisms driving sex hormone effects on reward-related behaviors. In this proposal, by taking advantage of the most recent technologies to define, manipulate, and monitor neural activity, I plan to test the functional contribution of specific hormone receptors on molecularly defined LHb projection neurons on reward and aversion-related behaviors.