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.

抽象的 海马体在记忆的初始形成和存储中具有明确的作用。 然而，人们对支持重组和恢复的大脑机制知之甚少。 将记忆转移到长期皮质存储中 对海马体的详细了解。 皮质整合对于揭示长期记忆的调节至关重要，以及如何 它们可能变得太短暂（如阿尔茨海默氏症、帕金森氏症、创伤性脑损伤）或太短暂 持续的（如创伤后应激障碍）是一项挑战，是实时跟踪所固有的困难。 数周至数月内多个大脑区域的细胞分辨率活动 为此，我们最近开发了一种头部固定行为。 范式，与纵向成像兼容，小鼠学习形成和主要上下文 我们还发现，学习这项任务需要至少一个月的时间。 海马体，而记忆巩固则需要内嗅皮层和前额叶皮层。 执行多区域纵向神经活动记录的方法，以及 成像过程中解剖学定义的光遗传学抑制，我们建议剖析实时 海马-内嗅-前额叶通路在记忆巩固中的贡献。 具体来说，我们的目标是描述一种新的记忆巩固行为模型（目标 1），以及 进行纵向成像以识别前额叶皮层独特的大脑活动模式 最后，我们将确定内嗅投射如何稳定这种记忆。 巩固期间前额皮质的活动模式（目标 3），我们将共同做出贡献。 我们对某些记忆如何逐渐重组和稳定的理解 大脑进行长期储存。