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

焦虑表征的腹侧海马编码是由丘脑输入决定的。

• 批准号: 10723104
• 负责人: Mark M Gergues
• 金额: $ 4.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10723104
• 关键词: Adaptive Behaviors; Adult; Affective; American; Amygdaloid structure; Anatomy; Animals; Anterior; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Area; Behavior; Behavioral; Brain; Brain region; Calcium; California; Cells; Charge; Communities; Complex; Conflict (Psychology); Electrophysiology (science); Emotional; Environment; Financial Hardship; Foundations; Fright; Functional disorder; Future; Generations; Genetic; Goals; Heterogeneity; Hippocampus; Hypothalamic structure; Lateral; Learning; Lesion; Medial; Methods; Mood Disorders; Moods; Neurons; Neurosciences; Optics; Output; Pathway interactions; Population; Positioning Attribute; Postdoctoral Fellow; Prefrontal Cortex; Publishing; Research; Research Project Grants; Research Proposals; Rewards; Role; San Francisco; Shapes; Solid; Source; Specific qualifier value; Stimulus; Structure of paraventricular nucleus of thalamus; Subthalamic structure; Techniques; Testing; Thalamic structure; Universities; Work; anxiety-related behavior; anxiety-related disorders; approach avoidance behavior; arm; avoidance behavior; behavioral response; brain behavior; brain cell; cell type; computerized tools; deep learning; effective therapy; emotional behavior; emotional stimulus; experimental study; innovation; insight; learning strategy; maladaptive behavior; nerve supply; neural circuit; neurobiological mechanism; neuropsychiatry; novel; novel therapeutic intervention; optogenetics; pharmacologic; tool; treatment of anxiety disorders

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.

项目摘要 近三分之一的美国成年人患有焦虑症，承受着巨大的个人、 社会和经济负担。推进新的更有效的焦虑症治疗方法的困难在于 因为它们是复杂的基于电路的条件，是由几个分布式区域的功能障碍引起的， 连接和产生正常适应性行为的细胞类型。因此，对 如果我们希望产生适应不良行为，那么神经回路如何被破坏以产生适应不良行为就至关重要 有效的治疗。最近的工作揭示了海马体（HPC），它通常被认为是 与学习有关，因为它在编码充满情感的环境和产生适当的情绪方面发挥着作用 行为反应。更具体地说，我们实验室的新证据已经确定了 HPC 神经元 投射到下丘脑的腹极编码焦虑环境并双向调节 回避行为。然而，如何以及哪些输入参与了与焦虑相关的表征的生成 腹侧 HPC 的作用仍不清楚。使用全脑细胞类型特定的解剖屏幕，我们确定了 丘脑室旁核 (PVT) 的前部，该区域涉及处理 显着的情绪刺激，作为 HPC 焦虑相关信息的假定来源。 在这里，我将结合使用尖端的光学、药理学和计算工具来 剖析和描述焦虑环境的丘脑-海马编码和焦虑控制 相关行为。这里完成的实验将提供第一个研究来探究 HPC 的编码方式 焦虑的背景和经典焦虑测试中丘脑的贡献。总而言之，这项研究将提供 关于电路如何对新事物产生过度回避（即与焦虑相关的行为）的重要见解 针对焦虑相关疾病的治疗干预。 所有提议的实验都是实验室中成熟的技术，并且是全球享有盛誉的研究的一部分 神经科学界，包括加州大学电路功能领域的杰出领先专家， 旧金山。因此，我已准备好并处于理想的世界一流环境中，以完成 成功且有影响力的博士论文。这里描述的工作符合我的总体学习目标 情感行为的神经回路控制，将为我未来的博士后工作打下坚实的基础。