Investigating Ventral CA1 Neural Representations of Anxiety-Like Behavior

项目摘要 检测和适当应对潜在威胁情况的能力对生存至关重要。 介导这些功能的神经系统的失调可导致病理性回避， 普通的环境和持续的迫在眉睫的威胁感，消极情绪的关键组成部分， 焦虑症的一种状态。许多研究已经开始揭示大脑区域和神经 控制回避行为和编码焦虑状态的回路。特别是腹侧海马体 已经成为情绪行为的关键节点，包括那些由焦虑环境引起的情绪行为。 我们的实验室和其他人已经发现腹侧CA 1的单个神经元亚群被厌恶性刺激激活， 环境，但这种选择性并不适用于不同的任务，用于分析焦虑样 行为此外，目前还不清楚腹侧海马体的哪些输入提供了情感信息 驱动焦虑相关的神经活动。腹侧海马体编码的机制 焦虑状态仍然是未知的，研究这个大脑区域如何代表这些情绪状态是一个很好的方法。 理解焦虑症的神经基础的重要一步。在这份提案中，我将利用 姿态估计算法和无监督行为分割（目标1），体内钙成像和 神经群体分析（目标2），沿着同时输入特异性光遗传学抑制和钙离子 成像（目的3），以表征焦虑样情绪状态的行为表现，并确定 它们是如何在腹侧海马体中编码的。成功完成这项研究将有助于阐明 腹侧海马体在焦虑中的作用，可能为发展 基于神经回路的疗法来治疗焦虑症。这些数据沿着研究和科学 通过这个Kirschstein-NRSA F30奖学金开发的专业知识将支持我的长期目标， 成为一名独立的科学家。

PROJECT SUMMARY The ability to detect and appropriately respond to potentially threatening situations is critical for survival. Dysregulation of the neural systems which mediate these functions can lead to pathological avoidance of ordinary environments and persistent feelings of imminent threat, key components of the negative emotional state characteristic of anxiety disorders. Many studies have begun to reveal the brain regions and neural circuits that control avoidance behavior and encode states of anxiety. Specifically, the ventral hippocampus has emerged as a critical node for emotional behaviors including those evoked by anxiogenic environments. Our lab and others have found that subpopulations of single neurons in ventral CA1 are activated by aversive environments, but this selectivity does not generalize across different tasks used to assay anxiety-like behavior. Moreover, it is unclear which inputs to the ventral hippocampus provide the emotional information that drives this anxiety-related neural activity. The mechanism by which the ventral hippocampus encodes anxiety states is still unknown and investigating how this brain region represents these emotional states is an essential step towards understanding the neural substrates of anxiety disorders. In this proposal, I will utilize pose estimation algorithms and unsupervised behavioral segmentation (Aim 1), in vivo calcium imaging and neural population analyses (Aim 2), along with simultaneous input-specific optogenetic inhibition and calcium imaging (Aim 3) to characterize the behavioral manifestations of anxiety-like emotional states and determine how they are encoded in the ventral hippocampus. Successful completion of this study will help to elucidate the role of the ventral hippocampus in anxiety, potentially opening new research avenues for the development of neural circuit based therapeutics to treat anxiety disorders. These data along with the research and scientific expertise developed through this Kirschstein-NRSA F30 Fellowship Award will support my long-term goal of becoming an independent physician-scientist.