Brain dynamics underlying long-term memory consolidation

长期记忆巩固背后的大脑动力学

• 批准号: 10658311
• 负责人: Priya Rajasethupathy
• 金额: $ 122.04万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658311
• 关键词: Alzheimer' s Disease; Anatomy; Animals; Behavior; Behavioral; Behavioral Model; Behavioral Paradigm; Bilateral; Brain; Brain imaging; Brain region; Calcium; Chronic; Data; Dependence; Head; Hippocampus; Human; Image; Learning; Lesion; Memory; Memory Loss; Methodology; Methods; Monitor; Mus; Neocortex; Neurologic; Parkinson Disease; Pathway interactions; Pattern; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Regulation; Resolution; Retrieval; Rewards; Role; Shapes; Site; Testing; Time; Traumatic Brain Injury; Work; conditioned fear; entorhinal cortex; forgetting; imaging modality; insight; long term memory; memory consolidation; memory retention; neocortical; neural; optogenetics; serial imaging; two-photon

Abstract The hippocampus has a well-established role in the initial formation and storage of memory. However, little is understood about brain mechanisms that support the re-organization and transfer of memories into longer-term cortical storage. A detailed understanding of hippocampal- to-cortical consolidation is critical to shed light on the regulation of long-term memories, and how they may become too transient (as in Alzheimer’s, Parkinson’s, Traumatic Brain Injury) or too persistent (as in PTSD). One challenge has been the difficulty inherent to tracking the real-time cellular resolution activity of multiple brain regions throughout the weeks-to-months long consolidation window. Toward this, we have recently developed a head-fixed behavioral paradigm, compatible with longitudinal imaging, where mice learn to form and main contextual associations for at least one month. We have also found that learning of this task requires the hippocampus, while memory consolidation requires the entorhinal and prefrontal cortex. Using methods to perform multi-region longitudinal neural activity recordings, together with anatomically-defined optogenetic inhibition during imaging, we propose to dissect the real-time contributions of the hippocampal-entorhinal-prefrontal pathway in memory consolidation. Specifically, we aim to characterize a new behavioral model of memory consolidation (aim 1), and perform longitudinal imaging to identify prefrontal cortex brain activity patterns unique to consolidated memories (aim 2). Finally, we will identify how entorhinal projections stabilize such activity patterns in prefrontal cortex during consolidation (aim 3). Together, we will contribute to our understanding of how some memories are progressively re-organized and stabilized across the brain for long-term storage.

摘要 海马体在记忆的初始形成和储存中具有公认的作用。 然而，人们对支持重组的大脑机制知之甚少， 将记忆转移到长期的皮层存储中。对海马的详细了解- 大脑皮层的巩固对于阐明长期记忆的调节至关重要， 他们可能会变得过于短暂（如阿尔茨海默氏症，帕金森氏症，创伤性脑损伤）或过于 持续性（如PTSD）。其中一个挑战是跟踪实时 在数周到数月的时间里， 整合窗口为此，我们最近开发了一种固定头部的行为 范例，与纵向成像兼容，其中小鼠学习形成和主要上下文 协会至少一个月。我们还发现，学习这项任务需要 记忆巩固需要内嗅和前额皮质。使用 进行多区域纵向神经活动记录的方法，以及 在成像过程中解剖学定义的光遗传学抑制，我们建议解剖实时 大脑皮层-内嗅-前额叶通路在记忆巩固中的作用 具体来说，我们的目标是描述一种新的记忆巩固行为模型（aim 1）， 进行纵向成像，以确定前额叶皮层大脑活动模式， 巩固记忆（目标2）。最后，我们将确定内嗅投射如何稳定这种 巩固期间前额叶皮层的活动模式（目标3）。我们将共同为 我们对一些记忆是如何逐渐重组和稳定的理解， 大脑进行长期储存。