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

项目摘要 这项建议试图通过以下方式来研究性激素对奖赏和厌恶相关行为的影响 外侧缰核(LHb)回路标测。LHb是编码厌恶信息的重要中心枢纽 协调有动机的行为，这些行为对生存至关重要。LHb依赖的回路功能障碍 导致了一系列不同的无序行为，例如正价和负价的异常处理， 快感缺乏、抑郁症状和适应不良的压力反应，仅举几例。虽然大家都知道 有动机的行为是由循环性激素调节的，还没有研究调查消极的行为是否 电路监管机构，特别是来自LHB的预测，促成了这种现象。此外，核能 大脑中的激素受体尚未得到很好的描述，因此了解它们在LHb中的作用 奖赏回路及其与循环荷尔蒙的相互作用将提供对性驱动机制的洞察 荷尔蒙对奖励相关行为的影响。在这项提案中，通过利用最新的 定义、操作和监控神经活动的技术，我计划测试特定的功能贡献 荷尔蒙受体在分子上定义了LHb投射神经元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.