Reorganization of cortical memory ensembles across time

项目摘要 对一件事的记忆可能会持续一生。某些经历可以在几分钟、几个月、 而在这一事件发生多年后。要做到这一点，大脑必须编码相关信息 从事件中保留它一段不确定的时间，然后在适当的时候检索该内存 暗示。先前的研究已经表明，在最近和最近的几年中，对恐惧经历的提取在行为上是相似的 记忆的远程提取时间，但调节该记忆的神经回路明显不同 跨越记忆时间线。简而言之，行为保持稳定，而神经活动是动态的。证据 这表明记忆是随着时间的推移而重新组织的--越来越多地涉及到一个分布式的皮质网络。 虽然我们已经确定了几个参与远程记忆的独立皮质区域，但我们的 对于它们如何相互作用以及这些变化的性质，我缺乏初步的数据 表明未被调查的内侧前额叶皮质(MPFC)投影坐标是遥远的，但不是最近的 通过投射到联想皮质的记忆。需要进一步的探索来确定具体的活动 随着时间的推移，记忆提取过程中这些电路中的模式。这些发现将揭示根本 大脑组织和检索随时间推移的显著经验的原则。 这项提案的总体目标是调查发生在 MPFC作为恐惧记忆的集合，从最近的重组到遥远的，并确定 这次重组。基于我导师发表的工作和我的初步发现，我的项目将 重点研究mPFC和听觉关联区之间的联系。为了解决这些问题，我将使用 建立mPFC-皮层联系的必要性和充分性的电路特异性光遗传学方法 用于远程存储的电路。这将解决这些mPFC投射神经元的功能作用。那我会的 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 时间点，以检查这些mPFC神经元如何编码以及行为和任务变量 记忆时间点。最后，我将用病毒-遗传学相结合的方法，给依赖活动的合奏贴上标签 同时使用全脑环路图来了解新近和 远程合奏及其下游连接。总而言之，这些目标将揭示对 记忆组织的时间依赖性变化并增强我们对mPFC功能的理解 组织大脑皮层网络，潜在地识别针对恐惧障碍治疗的改进电路 (例如，创伤后应激障碍)。

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).