Reorganization of cortical memory ensembles across time

皮质记忆群随时间的重组

• 批准号: 10680332
• 负责人: Zachary E Zeidler
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680332
• 关键词: Address; Age; Anatomy; Anxiety Disorders; Area; Auditory; Axon; Behavior; Behavior Control; Behavioral; Brain; Brain Mapping; Calcium; Cells; Coupling; Cues; Data; Disease; Event; Foundations; Freezing; Fright; Functional disorder; Future; Gene Expression; Goals; Head; Image; Immediate-Early Genes; Label; Light; Link; Maps; Medial; Mediating; Memory; Mentors; Methods; Microscope; Modeling; National Institute of Mental Health; Nature; Neurons; Output; Pattern; Pilot Projects; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Publishing; Research; Resistance; Retrieval; Role; Testing; Time; Tissues; Trauma; Viral Physiology; Work; association cortex; career; cell type; conditioned fear; design; effective intervention; emotional experience; experience; experimental study; fear memory; genetic approach; improved; insight; long term memory; memory recall; memory retrieval; neural; neural circuit; novel; optogenetics; prevent; recruit; symposium; therapeutic target; timeline; virus genetics

Project Summary Memory of a single event can last a lifetime. Certain experiences can guide behavior minutes, months, and years after the event has transpired. For this to happen, the brain must encode the relevant information from the event, retain it for an indeterminate amount of time, then retrieve that memory when given appropriate cues. Previous work has shown that retrieval of a fearful experience is behaviorally similar across recent and remote retrieval times of a memory, yet the neural circuits mediating that memory are importantly different across the memory timeline. In short, behavior remains stable while neural activity is dynamic. Evidence suggests that memories are reorganized across time – increasingly involve a distributed cortical network. Although we have identified several independent cortical regions that participate in remote memory, our understanding of how they interact at the and the nature of these changes is lacking My preliminary data indicates that an uninvestigated medial prefrontal cortex (mPFC) projection coordinates remote but not recent memory via projections to association cortex. Further exploration is needed to determine the specific activity patterns in these circuits during memory retrieval over time. These discoveries would reveal fundamental principles by which the brain organizes and retrieves salient experiences across time. The overall goal of this proposal is to investigate the cell-type specific changes that occur in mPFC ensembles as fear memories reorganize from recent to remote and to determine the nature of this reorganization. Based on published work from my mentor and my preliminary findings, my project will focus on the connection between mPFC and auditory association areas. To address these questions, I will use circuit-specific, optogenetic approaches to establish necessity and sufficiency of a mPFC–cortical association circuit for remote memory. This will address the functional role of these mPFC projection neurons. I will then use freely-moving calcium imaging to record the activity of these cells at both recent and remote memory timepoints in order to examine how these mPFC neurons encode and behavior and task variables across memory timepoints. Finally, with a combined viral-genetic approach, I will label activity-dependent ensembles while employing whole-brain circuit mapping to understand the anatomical relationship between recent and remote ensembles and their downstream connections. Together, these aims will reveal novel insights into the time-dependent changes in memory organization and enhance our understanding of mPFC function in organizing cortical networks, potentially identifying improved circuits to target for treatment of fear disorders (e.g. Post Traumatic Stress Disorder).

项目摘要 一个单一事件的记忆可以持续一生。某些经历可以在几分钟，几个月， 在事件发生多年后。要做到这一点，大脑必须对相关信息进行编码 从事件中，将其保留一段不确定的时间，然后在适当的时候检索该记忆 线索以前的研究表明，在最近和最近的一段时间里， 远程检索时间的记忆，但神经回路介导的记忆是重要的不同 在记忆的时间轴上简而言之，行为保持稳定，而神经活动是动态的。证据 这表明记忆是跨时间重组的-越来越多地涉及分布式皮层网络。 虽然我们已经确定了几个独立的参与远程记忆的皮层区域， 了解他们如何相互作用，这些变化的性质是缺乏我的初步数据 表明一个未经调查的内侧前额叶皮层（mPFC）投影协调远程，但不是最近的 通过投射到联想皮层来记忆。需要进一步探索以确定具体活性 在记忆提取过程中这些回路的模式。这些发现揭示了 大脑组织和检索时间上显著经验的原则。 这项提案的总体目标是调查细胞类型发生的具体变化， mPFC集合作为恐惧记忆重组，从最近到遥远，并确定的性质， 这次重组。基于我的导师发表的工作和我的初步发现，我的项目将 重点关注mPFC和听觉联想区之间的联系。为了解决这些问题，我将使用 回路特异性光遗传学方法来确定mPFC-皮质关联的必要性和充分性 用于远程存储器的电路。这将解决这些mPFC投射神经元的功能作用。然后我将 使用自由移动的钙成像来记录这些细胞在最近和远程记忆中的活动， 为了检查这些mPFC神经元如何编码以及行为和任务变量， 记忆时间点。最后，结合病毒遗传学方法，我将标记活性依赖性集合 同时采用全脑回路映射来理解最近和最近的脑电活动之间的解剖关系， 远程集合及其下游连接。总之，这些目标将揭示新的见解， 记忆组织的时间依赖性变化，并增强我们对mPFC功能的理解， 组织皮层网络，潜在地识别改善的回路，以治疗恐惧症 (e.g.创伤后应激障碍）。