Role of novel projection-defined basal amygdala subregions in fear memory expression

新的投影定义的基底杏仁核亚区在恐惧记忆表达中的作用

• 批准号: 10748146
• 负责人: Frank Zamudio
• 金额: $ 4.34万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10748146
• 关键词: Affect; Amygdaloid structure; Anatomy; Anterior; Anxiety; Area; Attention; Behavior; Behavior assessment; Behavioral; Brain; Brain Diseases; Brain region; Calcium; Career Exploration; Characteristics; Communication; Complex; Disease; Electrophysiology (science); Ensure; Environment; Equipment; Exposure to; Extinction; Fiber; Fostering; Foundations; Fright; Future; Generations; Genetic; Hippocampus; Hypothalamic structure; Image; Label; Lateral; Learning; Link; Maps; Measures; Medial; Memory; Mental Depression; Mentorship; Morphology; Mus; Neurons; Neurosciences; Outcome; Output; Pattern; Photometry; Post-Traumatic Stress Disorders; Productivity; Research; Research Personnel; Retrieval; Rewards; Role; Science; Shock; Taste Perception; Testing; Training; Universities; Viral; Visceral; Visual; behavioral outcome; career; conditioned fear; connectome; design; emotional behavior; experimental study; fear memory; in vivo; insight; learning extinction; memory retrieval; mouse model; novel; optogenetics; prevent; response; segregation; stem; training opportunity; visual processing

PROJECT SUMMARY/ABSTRACT The basal amygdala (BA) has been shown to be involved in valence-specific behaviors, including fear learning and reward behaviors. These behaviors are linked not only to genetic, anatomical, morphological, and electrophysiological characteristics of the BA, but also the various inputs and outputs of the BA. Current research has revealed the presence of four novel projection-defined subregions within the BA, each with unique brain connections that can underlie their function. Understanding learning and memory associated with the BA is especially important considering how dysregulation of tightly regulated emotional behaviors and associations can contribute to anxiety, depression, and PTSD. Therefore, understanding how information flows through the BA and its subregions along with the involvement of neuronal projections coming in and out of the BA is necessary to understand these disorders. This proposal combines brain-wide activity mapping along with in vivo calcium activity recording and neuronal manipulation to test the role of projection-defined BA subregions in the retrieval of fear and fear extinction memories. Recent advances in the characterization of BA regional connectivity will be employed to examine neuronal activity within each of the four BA subregions’ connectomes using a mouse model that can label active neurons brain-wide (Aim 1A). Next, retrogradely labeled subpopulations unique for each of the four BA subregions will be subjected to in vivo calcium activity recordings (Aim 1B) and optogenetic manipulations (Aim 2). Collectively, these aims will provide information on the correlative activity of direct inputs and outputs into and stemming from each BA subregion, activity of each BA subregion in valence-specific behaviors with particular attention to fear and extinction memories, and possible causal contributions of each BA subregion neuronal activity to fear and extinction memory expression. For successful completion of this project, the applicant will be thoroughly trained in brain-wide imaging of neuronal activity, fiber photometry, and optogenetic manipulations. In addition, the applicant will be provided with numerous opportunities for training in science communication, mentorship, and career exploration. The Reijmers and Maguire labs at Tufts University foster an environment where the applicant will be intellectually engaged and supported with all necessary facility, equipment, and guiding to ensure productive graduate training, and to prepare the applicant for a flourishing career as an independent researcher in neuroscience.

项目概要/摘要 基底杏仁核 (BA) 已被证明参与特定价行为，包括恐惧学习 和奖励行为。这些行为不仅与遗传、解剖学、形态学和 BA 的电生理特性，以及 BA 的各种输入和输出。目前的研究 揭示了 BA 内存在四个新颖的​​投影定义子区域，每个子区域都有独特的大脑 可以作为其功能基础的连接。了解与 BA 相关的学习和记忆是 尤其重要的是考虑到严格调节的情绪行为和关联如何失调 可能会导致焦虑、抑郁和创伤后应激障碍 (PTSD)。因此，了解信息如何在网络中流动 BA 及其子区域以及进出 BA 的神经元投射的参与 有必要了解这些疾病。 该提案将全脑活动映射与体内钙活动记录和神经元活动结合起来 测试投影定义的 BA 子区域在恐惧恢复和恐惧消退中的作用 回忆。 BA 区域连通性表征的最新进展将用于检查 使用可以标记活动的小鼠模型来观察四个 BA 亚区连接组中每个区域内的神经元活动 全脑神经元（目标 1A）。接下来，四个 BA 中每一个的逆行标记亚群都是独特的 子区域将接受体内钙活性记录（目标 1B）和光遗传学操作（目标 2）。总的来说，这些目标将提供有关直接投入和产出的相关活动的信息 源于每个 BA 子区域，每个 BA 子区域在价态特定行为中的活性具有特定的 注意恐惧和消退记忆，以及每个 BA 亚区神经元可能的因果贡献 活动以恐惧和消退记忆的表达为主。 为了成功完成该项目，申请人将接受全脑成像方面的全面培训 神经元活动、纤维光度测定和光遗传学操作。此外，申请人还将获得 科学传播、指导和职业探索方面的大量培训机会。赖杰默斯 塔夫茨大学的马奎尔实验室和马奎尔实验室营造了一个让申请人能够进行智力参与和 提供所有必要的设施、设备和指导支持，以确保富有成效的研究生培训，并 帮助申请人为作为神经科学独立研究员的蓬勃发展的职业生涯做好准备。