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.

项目总结/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 奖励行为。这些行为不仅与遗传、解剖、形态和 除了BA的电生理特性之外，还包括BA的各种输入和输出。目前的研究 揭示了BA内存在四个新的投影定义的子区域，每个区域都有独特的大脑 这些连接可以支撑它们的功能。理解与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的失调 会导致焦虑抑郁和创伤后应激障碍因此，了解信息如何通过 BA及其沿着亚区与进出BA的神经元投射的参与， 需要了解这些疾病。 该提议将全脑活动映射沿着与体内钙活动记录和神经元活动记录相结合。 操纵测试的作用，投影定义的BA亚区在检索的恐惧和恐惧灭绝 回忆最新进展的表征BA区域连接将被用来检查 使用可以标记活性的小鼠模型，在四个BA亚区的连接体中的每一个内的神经元活动 全脑神经元（Aim 1A）。接下来，对四个BA中的每一个都独特的逆行标记亚群， 亚区将进行体内钙活性记录（Aim 1B）和光遗传学操作（Aim 2）。总的来说，这些目标将提供关于直接投入和产出的相关活动的信息， 源于每个BA亚区，每个BA亚区的活性在价特异性行为中具有特定的 注意恐惧和灭绝记忆，以及每个BA亚区神经元的可能因果贡献 活动到恐惧和灭绝记忆的表达。 为了成功完成这个项目，申请人将接受全面的全脑成像培训， 神经元活动、纤维光度测定和光遗传学操作。此外，申请人将获得 在科学传播，指导和职业探索培训的众多机会。赖默夫妇 塔夫茨大学的马奎尔实验室营造了一个让申请人智力投入的环境， 支持所有必要的设施，设备和指导，以确保生产性的研究生培训，并 为申请人作为神经科学独立研究人员的蓬勃发展做好准备。