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.

项目摘要/摘要 基底杏仁核（BA）已被证明参与了价值特定的行为，包括恐惧学习 并奖励行为。这些行为不仅与遗传，解剖学，形态学和 BA的电生理特征，以及BA的各种输入和输出。当前的研究 已经揭示了BA中有四个新型投影定义的子区域，每个区域都有独特的大脑 可以构成其功能的连接。了解与BA相关的学习和记忆是 考虑到如何严格调节的情绪行为和关联的失调，特别重要 可以导致焦虑，抑郁和PTSD。因此，了解信息如何流过 BA及其子区域以及从BA进出神经元预测的参与是 了解这些疾病所必需的。 该建议结合了整个大脑活动映射以及体内钙活性记录和神经元 操纵测试投影定义的BA子区域在恐惧和恐惧扩展中的作用 回忆。 BA区域连通性表征的最新进展将被雇用进行考试 使用鼠标模型，可以在四个BA子区域连接组中的每一个中的每一个中的神经元活性 神经元在整个脑中（AIM 1A）。下一 子区域将受到体内钙活性记录（AIM 1B）和光遗传操作（AIM 2）。总的来说，这些目标将提供有关直接输入和输出到和输出的正确活动的信息 由每个BA子区域造成，每个BA子区域的活性特异性行为 注意恐惧和扩展记忆，以及每个BA子区域神经元的可能因果关系 恐惧和扩展记忆表达的活动。 为了成功完成该项目，将对申请人进行全面培训 神经元活性，纤维光度法和光遗传操作。此外，将为申请人提供 科学沟通，指导和职业探索方面的培训众多机会。 Reijmers 塔夫茨大学（Tufts University）的马奎尔（Maguire Labs 支持所有必要的设施，设备和指导，以确保产品研究生培训以及 作为神经科学领域的独立研究员，为申请人做好了蓬勃发展的职业。