Thalamic inputs modulate anxiety-related representations in the hippocampus

丘脑输入调节海马体中与焦虑相关的表征

基本信息

批准号：
10464708
负责人：
Mark M Gergues
金额：
$ 2万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2022-09-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10464708
关键词：
Adaptive Behaviors Adult American Amygdaloid structure Anatomy Animals Anterior Anti-Anxiety Agents Anxiety Anxiety Disorders Area Behavior Brain Calcium California Cells Charge Communities Complex Conflict (Psychology)Emotional Environment Equilibrium Financial Hardship Fright Functional disorder Generations Heterogeneity Hippocampus (Brain)Hypothalamic structure Image Lateral Lead Learning Lesion Medial Mood Disorders Moods Mus Neurons Neurosciences Optics Output Pathway interactions Pharmacology Population Positioning Attribute Prefrontal Cortex Process Publishing Research Proposals Rewards Role San Francisco Shapes Source Stimulus Structure of paraventricular nucleus of thalamus Synapses Techniques Testing Tetanus Toxin Thalamic structure Universities Viral Work anxiety-related behavior anxiety-related disorders approach avoidance behavior arm avoidance behavior base behavioral response brain cell cell type computerized tools designer receptors exclusively activated by designer drugs effective therapy emotion regulation emotional behavior emotional stimulus experimental study field study innovation insight maladaptive behavior neural circuit neurobiological mechanism neuropsychiatry novel novel therapeutic intervention optogenetics tool treatment of anxiety disorders

Adaptive Behaviors Adult American Amygdaloid structure Anatomy Animals Anterior Anti-Anxiety Agents Anxiety Anxiety Disorders Area Behavior Brain Calcium California Cells Charge Communities Complex Conflict (Psychology)Emotional Environment Equilibrium Financial Hardship Fright Functional disorder Generations Heterogeneity Hippocampus (Brain)Hypothalamic structure Image Lateral Lead Learning Lesion Medial Mood Disorders Moods Mus Neurons Neurosciences Optics Output Pathway interactions Pharmacology Population Positioning Attribute Prefrontal Cortex Process Publishing Research Proposals Rewards Role San Francisco Shapes Source Stimulus Structure of paraventricular nucleus of thalamus Synapses Techniques Testing Tetanus Toxin Thalamic structure Universities Viral Work anxiety-related behavior anxiety-related disorders approach avoidance behavior arm avoidance behavior base behavioral response brain cell cell type computerized tools designer receptors exclusively activated by designer drugs effective therapy emotion regulation emotional behavior emotional stimulus experimental study field study innovation insight maladaptive behavior neural circuit neurobiological mechanism neuropsychiatry novel novel therapeutic intervention optogenetics tool treatment of anxiety disorders

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项目摘要

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.

项目摘要几乎三分之一的成年美国人患有焦虑症，带有巨大的个人，社会和经济负担。难以推进新颖的焦虑症治疗方法是因为它们是基于电路的复杂条件，原因是在几个分布式区域的功能障碍引起的，所以连接和产生正常自适应行为的细胞类型。因此，对如果我们希望产生，神经回路如何被破坏以产生适应不良的行为至关重要有影响力的治疗方法。最近的工作揭示了海马（HPC），这是经典的与学习有关，因为它在编码情感充满电的环境中的作用并产生合适的环境行为反应。更具体地说，来自我们实验室的新兴证据已经确定了HPC神经元中的HPC神经元该项目的下丘脑腹板编码焦虑生成环境和双向调节回避行为。然而，与焦虑相关表示的产生如何以及哪些输入涉及在腹侧，HPC仍然未知。使用全脑细胞类型特定的解剖屏幕，我们确定了丘脑（PVT）的室室核的前部，该区域与加工有关显着的情绪刺激，作为HPC与焦虑有关的信息的推定来源。在这里，我将使用尖端的光学，药理和计算工具的组合来剖析和表征焦虑症的丘脑 - 海马编码以及焦虑的控制相关行为。这里完成的实验将提供第一批研究，以询问HPC如何编码焦虑的环境和丘脑在经典焦虑测试中的贡献。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）的关键见解与焦虑有关的疾病的治疗干预措施。所有提出的实验都是实验室中良好的技术，也是全球享有声望的一部分神经科学社区，包括加利福尼亚大学巡回功能的著名领先专家，旧金山。因此，我在理想的世界一流环境中被固定和定位，以完成成功而有影响力的博士学位论文。