Hippocampal modulation of subcortical circuits in the control of emotional behavior

海马调节皮层下回路控制情绪行为

基本信息

批准号：
10553661
负责人：
Mazen A Kheirbek
金额：
$ 57.92万
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：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10553661
关键词：
Adaptive Behaviors Adopted Adult American Amygdaloid structure Anatomy Anxiety Anxiety Disorders Area Arousal Axon Beds Behavior Behavior Control Behavior assessment Behavioral Biological Assay Cell Nucleus Classification Complex Conflict (Psychology)Data Detection Electrophysiology (science)Emotional Financial Hardship Fright Functional Imaging Functional disorder Funding Gene Expression Profiling Generations Goals Hippocampus Hypothalamic structure Image Lateral Learning Maps Mediating Moods Mus Neurons Optics Organizational Productivity Output Population Property Publishing Resolution Role Shapes Slice Stimulus Stress Structure Structure of paraventricular nucleus of thalamus Testing Thalamic structure Therapeutic Work anatomical tracing anxiety-like behavior anxiety-related behavior anxiety-related disorders avoidance behavior behavioral response biological adaptation to stress cell type emotional behavior experimental study hypothalamic-pituitary-adrenal axis innovation maladaptive behavior microendoscope nerve supply neural circuit neurophysiology neuroregulation novel optogenetics tool treatment of anxiety disorders

项目摘要

Project Summary Almost a third of adult Americans suffer from an anxiety disorder, carrying an enormous personal, societal and financial burden. Anxiety disorders are complex circuit-based conditions, resulting from dysfunction in a number of distributed regions, connections, and cell types that generate normal adaptive behavior. Thus, a deeper understanding of how these neural circuits become disrupted to generate maladaptive behavior is crucial if we hope to generate new treatments. In recent years, we have shown that the ventral hippocampus (vHPC) is an central node in the extended circuit that generates adaptive avoidance behavior. However, the input- output organization of the ventral hippocampus in the control of anxiety-related behavior remains poorly understood. Here, we will use functional imaging of large populations of anatomically defined vHPC neurons, optical manipulation of these neurons, and high resolution behavioral analyses to expand our understanding of how the extended ventral hippocampal network controls behavior. We will first determine the encoding properties of vHPC output neurons to subcortical areas known to drive avoidance and anxiety-like behavior. Then, we will adopt new unsupervised behavioral classification tools for understanding anxiety-related behavior in mice to determine how vHPC projection neurons orchestrate distinct behavioral states. Finally, we will determine how distinct inputs to the differentially modulate avoidance behavior and shape anxiety-related representations in vHPC. This will provide the most detailed functional map of the extended hippocampal circuit that controls avoidance behavior, and provide novel targets for generation of therapeutics for the treatment of anxiety disorders.

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。焦虑症是基于电路的复杂条件，由许多分布式区域，连接和单元类型中的功能障碍引起的产生正常的自适应行为。因此，对这些神经回路的更深入了解如果我们希望生成新治疗。近年来，我们表明腹侧海马（VHPC）是中心在扩展电路中产生自适应回避行为的节点。但是，输入 - 腹侧海马的输出组织控制焦虑相关行为仍然很了解。在这里，我们将使用大量人群的功能成像解剖定义的VHPC神经元，这些神经元的光学操纵和高分辨率行为分析以扩展我们对延伸腹侧海马的理解网络控制行为。我们将首先确定VHPC输出的编码属性神经元到皮层下区域已知，以推动回避和焦虑行为。然后，我们会的采用新的无监督行为分类工具来理解与焦虑有关的小鼠的行为以确定VHPC投影神经元如何编排不同的行为国家。最后，我们将确定如何对差异调制回避的不同输入 VHPC中的行为和形状与焦虑相关的表示。这将提供最详细的控制回避行为的扩展海马电路的功能图，并为治疗焦虑症的治疗提供新的靶标。