Hippocampal sharp-wave ripple and replay mechanisms underlying long-term memory

海马尖波波纹和长期记忆的重放机制

基本信息

批准号：
10563365
负责人：
Jennifer Ding
金额：
$ 6.91万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10563365
关键词：
Affect Alzheimer&apos s Disease Alzheimer&apos s disease patient Amnesia Behavior Behavioral Bilateral Brain Calcium Cells Chronic Clinical Code Dementia Development Disease Electrodes Electrophysiology (science)Event Foundations Frequencies High Frequency Oscillation Hippocampus Hour Image Impairment Investigation Knowledge Maps Measures Memory Memory Disorders Memory impairment Methods Nature Optics Pathology Patients Pattern Performance Population Process Protocols documentation Recurrence Rest Role Shapes Short-Term Memory Sleep Speed Stable Populations Structure Task Performances Techniques Technology Testing Time Work awake detection method effective intervention effective therapy experience experimental study hippocampal pyramidal neuron improved in vivo in vivo calcium imaging insight long term memory memory consolidation memory encoding memory process memory recall network architecture neural neuromechanism novel therapeutics optogenetics preservation recruit sensor spatial memory two-photon virtual reality environment

Affect Alzheimer&apos s Disease Alzheimer&apos s disease patient Amnesia Behavior Behavioral Bilateral Brain Calcium Cells Chronic Clinical Code Dementia Development Disease Electrodes Electrophysiology (science)Event Foundations Frequencies High Frequency Oscillation Hippocampus Hour Image Impairment Investigation Knowledge Maps Measures Memory Memory Disorders Memory impairment Methods Nature Optics Pathology Patients Pattern Performance Population Process Protocols documentation Recurrence Rest Role Shapes Short-Term Memory Sleep Speed Stable Populations Structure Task Performances Techniques Technology Testing Time Work awake detection method effective intervention effective therapy experience experimental study hippocampal pyramidal neuron improved in vivo in vivo calcium imaging insight long term memory memory consolidation memory encoding memory process memory recall network architecture neural neuromechanism novel therapeutics optogenetics preservation recruit sensor spatial memory two-photon virtual reality environment

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项目摘要

Project summary The mammalian brain has the remarkable capacity to store and retrieve memories. In particular, salient events called sharp-wave ripples (SWRs) are implicated in the consolidation and recall of memories in the hippocampus. These events are high frequency oscillations caused by synchronous depolarizations across both hippocampal hemispheres, and they occur during awake rest or sleep. During SWRs, neural ensembles that are activated during awake experiences are reactivated in rest in compressed sequences of short durations, a process called ‘replay’. Because of their large-scale nature, sharp-wave ripples and replay events can potentially shape plasticity within hippocampal ensembles to promote memory. Studies have shown that lengthening the duration of SWRs can improve memory on spatial tasks performed less than 24 hours later, while disrupting SWRs will impair memory on these spatial tasks. Though SWRs can influence memory processes on short timescales, their role in preserving memories across long timescales remains largely unknown. This proposal will explore the hypothesis that SWRs enhance the stability of long-term memories by generating plasticity to form and maintain ensembles. We will investigate how SWRs shape the stability of spatial memories encoded in hippocampal region CA1 during navigation in virtual reality environments. This study will address two aims. In Aim 1, we will measure the effects SWRs have on the stability of the population-wide place code and replay events across weeks. The proposed experiments will leverage in vivo two-photon calcium imaging and electrophysiological recordings to evaluate whether SWRs causally create stable ensembles on the population level across weeks. In Aim 2, we will determine how SWRs and replay events shape microcircuit organization within replay ensembles. These experiments will utilize a high-speed two-photon optogenetic stimulation approach to optically measure causal functional connectivity between cells within the replay ensemble and to determine whether SWRs can generate plasticity to recruit cells into the replay ensemble. We hypothesize that SWRs contribute to establishing temporally stable memory traces by strengthening the causal functional connections within replay ensembles. These results will provide insight on neural mechanisms that stabilize memory ensembles across long timescales, which is critical for understanding how long-term memory processes are implemented. Long-term memory is impaired in patients with memory disorders and conditions such as Alzheimer’s disease, dementia, and amnesia, so findings from this proposal will help provide a foundation for understanding the pathology of these conditions and will help in the development of new therapies for these patients.

项目摘要哺乳动物的大脑具有出色的存储和检索记忆的能力。特别是显着事件在海马中的记忆的巩固和回忆中，实施了称为锋利的波浪波纹（SWR）。这些事件是由两个海马的同步沉积引起的高频振荡半球，它们发生在清醒的休息或睡眠期间。在SWR中，激活的神经合奏在清醒的过程中，在短时间的压缩序列中静止地重新激活，这一过程称为 “重播”。由于其大规模的性质，锋利的波浪和重播事件可能会形成海马集合中的可塑性以促进记忆。研究表明，延长持续时间 SWR可以改善不到24小时后执行的空间任务的内存，而干扰SWR将会在这些空间任务上损害记忆。尽管SWR可以影响短时间的内存过程，但它们的记忆过程在保存长时间尺度的记忆中的作用在很大程度上是未知的。该建议将探索 SWR通过产生可塑性形成和维持可增强长期记忆的稳定性的假设合奏。我们将研究SWR如何塑造在海马区域CA1中编码的空间记忆的稳定性在虚拟现实环境中导航。这项研究将针对两个目标。在AIM 1中，我们将测量效果 SWR具有整个人口范围的地位代码的稳定性，并在几周内重播事件。提议实验将利用体内两光子钙成像和电生理记录来评估 SWR是否在几周内在人口水平上创建稳定的合奏。在AIM 2中，我们将确定SWR和重播事件如何塑造重播合奏中的微电路组织。这些实验将利用高速两光子光遗传学刺激方法光学测量因果重播集合中的单元格之间的功能连通性，并确定SWR是否可以生成可塑性将细胞募集到重播集合中。我们假设SWR有助于建立通过增强重播合奏中的因果功能连接来暂时稳定的存储器跟踪。这些结果将提供有关神经机制的洞察时间尺度，这对于了解如何实施长期记忆过程至关重要。长期记忆力障碍和疾病的患者（例如阿尔茨海默氏病），痴呆症，痴呆症患者的记忆力受损和健忘症，因此该提案的发现将有助于理解理解病理的基础这些条件，将有助于为这些患者开发新疗法。