Ventral hippocampal encoding of anxiety representations is shaped by thalamic input.

项目摘要 几乎三分之一的美国成年人患有焦虑症，携带着巨大的个人， 社会和经济负担。焦虑症的新的更有效的治疗方法很难推进 因为它们是复杂的基于电路的情况，由几个分布区域的功能障碍引起， 连接，以及产生正常适应行为的细胞类型。因此，从根本上理解 神经回路如何被破坏以产生不适应行为是至关重要的，如果我们希望 有效的治疗。最近的研究揭示了海马体(HPC)，这是经典的 与学习有关，因为它在编码充满情感的环境和生成适当的 行为反应。更具体地说，来自我们实验室的新证据已经在大脑中发现了HPC神经元 投射到下丘脑的腹极编码焦虑环境并进行双向调节 回避行为。然而，焦虑相关表征的生成是如何以及哪些输入参与的呢？ 腹侧HPC的分布尚不清楚。使用全脑细胞类型的特定解剖筛查，我们确定了 丘脑室旁核(PVT)的前部，这一区域与 显著的情绪刺激，作为HPC焦虑相关信息的推定来源。 在这里，我将使用尖端光学、药理学和计算工具的组合来 解剖和描述丘脑-海马体编码的焦虑症背景和焦虑控制- 相关行为。这里所做的实验将提供第一批研究HPC如何编码的研究 焦虑症的背景和丘脑在经典焦虑测试中的作用。总而言之，这项研究将提供 对电路如何产生过度回避(即与焦虑相关的行为)的关键洞察 焦虑相关障碍的治疗干预。 所有拟议的实验都是在实验室中成熟的技术，也是全球知名的 神经科学界，包括加州大学著名的电路功能领先专家， 旧金山。因此，我在一个理想的世界级环境中做好了准备，完成了 成功而有影响力的博士论文。这里描述的工作与我学习的总体目标是一致的 神经回路对情感行为的控制，将为我今后的博士后工作奠定坚实的基础。

Project Abstract Almost one third of adult Americans suffer from an anxiety disorder, carrying an enormous personal, societal, and financial burden. Difficulty advancing novel more effective treatments for anxiety disorders is because they are complex circuit-based conditions, resulting from dysfunction in several distributed regions, connections, and cell types that generate normal adaptive behavior. Thus, a fundamental understanding of how neural circuits become disrupted to generate maladaptive behavior is crucial if we hope to generate impactful treatments. Recent work has revealed the hippocampus (HPC), which has classically been implicated in learning, for its role in encoding emotionally charged environments and generating appropriate behavioral responses. More specifically, emerging evidence from our lab has identified HPC neurons in the ventral pole that project to the hypothalamus encode anxiogenic environments and bidirectionally modulate avoidance behavior. Yet how and which inputs are involved in the generation of anxiety-related representations in the ventral HPC remain unknown. Using a whole-brain cell-type specific anatomical screen, we identified the anterior portion of the paraventricular nucleus of the thalamus (PVT), an area implicated in the processing of salient emotional stimuli, as a putative source of anxiety-related information to the HPC. Here, I will use a combination of cutting-edge optical, pharmacological, and computational tools to dissect and characterize the thalamic-hippocampal encoding of anxiogenic contexts and control of anxiety- related behaviors. Experiments done here will provide the first studies to interrogate how HPC encodes anxiogenic contexts and the thalamic contribution in classical tests of anxiety. All in all, this study will provide crucial insight into how circuits generate excessive avoidance (i.e., anxiety-related behavior) for new therapeutic interventions for anxiety-related disorders. All proposed experiments are well established techniques in the lab and part of a globally prestigious neuroscience community, including prominent leading experts of circuit function, at The University of California, San Francisco. Consequently, I am poised and positioned in an ideal world-class environment for completing a successful and impactful doctoral dissertation. Work described here is in line with my overall goal of studying neural circuit control of affective behavior and will serve as a solid foundation for my future postdoctoral work.