Neural Mechanism for Successful Memory Access in the Cortico-Hippocampal Networks

皮质-海马网络中成功记忆访问的神经机制

• 批准号: 10189701
• 负责人: Jun Yamamoto
• 金额: $ 40.95万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10189701
• 关键词: Affect; Alzheimer' s Disease; Animal Model; Animals; Area; Behavior; Behavioral; Brain; Brain Diseases; Communication; Cyclophosphamide; Data; Dementia; Diagnostic; Dorsal; Electrophysiology (science); Episodic memory; Event; Fire - disasters; Future; Goals; Hippocampus (Brain); Human; Link; Measurement; Memory; Memory impairment; Modeling; Mus; Neurons; Outcomes Research; Pathway interactions; Patients; Phase; Play; Population; Psychoses; Research Proposals; Rest; Retrieval; Role; Running; Scheme; Schizophrenia; Short-Term Memory; Structure; System; Technology; Testing; Time; Transgenic Mice; Work; awake; entorhinal cortex; experimental study; in vivo; indexing; memory process; memory retrieval; neural circuit; neuromechanism; novel; optogenetics; relating to nervous system; success; theories

PROJECT SUMMARY Successful memory retrieval is one of the most important functions in our brain. Numerous studies have shown that hippocampal-entorhinal (HPC-EC) circuits play crucial roles in encoding and retrieval of specific episodic memories. Many human patients who suffer from Alzheimer's disease, dementia and the broad spectrum of psychosis, including schizophrenia, show various ranges of memory deficits along with the HPC-EC damage. However, little is known about how specific memories are accessed and formed into meaningful memories to accomplish given tasks, especially at the systems level. This proposal focuses on the neural dynamics for successful memory access and retrieval during episodic working memory tasks to elucidate the neural circuit mechanism in the hippocampal-cortical (HPC-CTX) network. My long-term goal is to elucidate neural dynamics during psychotic states and to establish novel early-stage diagnostic measurements / analyses in human patients that are hinted at by in vivo recordings in animal models. I have previously demonstrated two forms of memory access in the HPC-EC circuits that are crucial during episodic memory tasks. The first form is called `gamma phase synchrony', which was observed during the running period of a spatial working memory task when the animal was about to make turns at the junction point of a T-maze. The second form is called an `extended interregional ripple burst', a memory replay event that is made of alternating chains of burst activities within HPC- EC network during quiet awake or stopping periods on a large running maze. These two forms of memory access turned out to be crucial for subsequent spatial working memory behavior. However, the circuit mechanism or memory contents during these neural activities under different behavioral states are still unknown. Revealing such memory contents during the memory access period will be crucial to understanding of how exactly our memory system works. We hypothesize that (i) the content of burst activities between HPC and EC index each other to retrieve longer episodes as an inter-regional communication during the off-line state and then (ii) the previously potentiated or activated group of neurons gets briefly activated in gamma phase synchrony during the active state to successfully execute the memory process. We will test three hypotheses in this proposal by combining transgenic mouse technology, circuit specific optogenetics, large-scale in vivo electrophysiology, and a spatial working memory task in mice. The first two specific aims will focus on neural content decoding during two forms of memory access and the third specific aim will investigate whether the two distinct forms of memory process have a causal relationship on the successful accession of memory in the HPC-EC network.

项目摘要 成功的记忆提取是我们大脑中最重要的功能之一。大量研究表明 HPC-EC回路在特定情景的编码和提取中起着重要作用， 回忆许多患有阿尔茨海默病、痴呆症和广泛的 包括精神分裂症在内的精神病表现出各种范围的记忆缺陷，沿着HPC-EC损伤。 然而，关于特定记忆是如何被访问并形成有意义的记忆， 完成给定的任务，特别是在系统级。该建议侧重于神经动力学， 在情景工作记忆任务中成功的记忆访问和提取，以阐明神经回路 HPC-CTX网络中的机制。我的长期目标是阐明神经动力学 并在人类患者中建立新的早期诊断测量/分析 这是通过动物模型的体内记录暗示的。我之前已经展示了两种形式的记忆 HPC-EC回路中的通路，这在情景记忆任务中至关重要。第一种形式称为“gamma 在空间工作记忆任务的运行过程中， 动物即将在T型迷宫的交叉点转弯。第二种形式被称为“扩展 区域间涟漪突发”，一种由HPC内交替的突发活动链组成的内存重播事件- 在大型迷宫中安静清醒或停止期间的EC网络。这两种形式的内存访问 对随后的空间工作记忆行为至关重要。然而，电路机制或 在不同的行为状态下，这些神经活动的记忆内容仍然是未知的。揭示 在存储器访问期间的这种存储器内容对于理解我们的 记忆系统工作。我们假设：（1）HPC和EC指数之间的爆发活动的内容， 另一个用于在离线状态期间检索更长的片段作为区域间通信，然后（ii） 先前增强或激活的神经元组在伽马相位同步期间被短暂激活。 激活状态以成功执行内存进程。我们将测试三个假设在这个建议， 结合转基因小鼠技术、电路特异性光遗传学、大规模体内电生理学，以及 小鼠的空间工作记忆任务。前两个具体目标将集中在神经内容解码过程中， 两种形式的记忆访问和第三个具体目标将调查是否两种不同形式的记忆 HPC-EC网络中记忆的成功加入与HPC-EC过程有因果关系。