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 杏仁核(BA)参与了包括恐惧学习在内的价特异性行为。 以及奖励行为。这些行为不仅与遗传、解剖、形态和 BA的电生理特性，也是BA的各种输入输出。当前的研究 揭示了BA内存在四个新的投影定义的亚区，每个亚区都有独特的大脑 可以作为其功能基础的联系。理解与BA相关的学习和记忆是 尤其重要的是，考虑到严格监管的情绪行为和联系的失调 会导致焦虑、抑郁和创伤后应激障碍。因此，了解信息如何在 BA及其亚区伴随着进出BA的神经元投射的参与是 是理解这些障碍所必需的。 这一建议结合了全脑活动图以及活体钙活动记录和神经元 测试投影定义的BA亚区在提取恐惧和恐惧消退中的作用的操作 回忆。将利用BA区域连通性表征方面的最新进展来研究 使用可以标记活性的小鼠模型，在四个BA亚区的每个连接中的神经元活动 全脑神经元(目标1A)。接下来，四个BA中每一个都有唯一的退化标记的亚种群 亚区将接受体内钙活动记录(AIM 1B)和光遗传操作(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亚区的活性在特定的价态行为中具有 注意恐惧和消亡记忆，以及每个BA亚区神经元可能的因果贡献 活动以恐惧和消亡记忆表达。 为了成功完成这个项目，申请者将接受全面的脑部成像培训。 神经细胞活动、纤维光度学和光遗传操作。此外，申请人将获提供 在科学交流、指导和职业探索方面有大量的培训机会。雷默一家 塔夫茨大学的马奎尔实验室培养了一种环境，在这种环境中，申请者将进行智力投入，并 支持所有必要的设施、设备和指导，以确保有成效的研究生培训，并 为申请者在神经科学领域的独立研究人员的职业生涯做好准备。