Investigating Ventral CA1 Neural Representations of Anxiety-Like Behavior

项目总结 发现并适当应对潜在威胁情况的能力对生存至关重要。 调节这些功能的神经系统失调可导致病理性回避 普通环境和持续感受到的迫在眉睫的威胁，是负面情绪的关键组成部分 焦虑症的状态特征。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电路。具体来说，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行为。 我们的实验室和其他人发现，腹侧CA1区单个神经元的亚群被厌恶激活 环境，但这种选择性并不适用于用于评估类焦虑的不同任务 行为。此外，还不清楚腹侧海马区的哪些输入提供了情绪信息 这驱动了这种与焦虑相关的神经活动。腹侧海马体编码的机制 焦虑状态仍是未知的，研究大脑区域如何代表这些情绪状态是一个 了解焦虑症的神经基础的关键一步。在这个提案中，我将利用 姿势估计算法和非监督行为分割(目标1)，活体钙成像和 神经细胞群体分析(目标2)，以及同时输入特异性光遗传抑制和钙 成像(目标3)描述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。这项研究的成功完成将有助于阐明 腹侧海马体在焦虑中的作用，可能为发展的新的研究途径 基于神经回路的疗法治疗焦虑症。这些数据伴随着研究和科学 通过Kirschstein-NRSA F30奖学金奖获得的专业知识将支持我的长期目标 成为独立的内科医生兼科学家。

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.