Functional Role of Hippocampal Neuronal Representations

海马神经元表征的功能作用

• 批准号: 7942805
• 负责人: Howard B. Eichenbaum
• 金额: $ 33.97万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7942805
• 关键词: Address; Animal Behavior; Animals; Behavior; Behavioral; Cells; Code; Computer Simulation; Data; Dorsal; Electric Stimulation; Fire - disasters; Future; Goals; Hippocampal Formation; Hippocampus (Brain); Learning; Left; Length; Link; Location; Maps; Memory; Memory Disorders; Methods; Modeling; Neurons; Pattern; Performance; Phase; Plastics; Play; Population; Positioning Attribute; Pyramidal Cells; Rattus; Research Personnel; Retrieval; Rewards; Role; Sampling; Structure; Testing; Theta Rhythm; Time; Training; Work; animal data; density; entorhinal cortex; episodic like memory; experience; high risk; hippocampal subregions; memory encoding; phase change; programs; receptive field; relating to nervous system; research study; response; sequence learning; theories; trend

The hippocampus is believed to be necessary for learning sequences and for disambiguation, and computational models predict that different subregions of the hippocampal formation play distinct roles in memory. However, these predictions have not been tested experimentally, and no one has demonstrated a causal relationship between patterns of activity in hippocampus and animal behavior. This project will address both issues in animals performing a delayed non-match to place (DNMP) task in a "T" maze. In Aim 1, we will study the emergence of context-sensitive sequences neural activity in region CA1 of dorsal hippocampus as animals learn the task, and compare activity from the Sample, Delay, and Choice phases of the task in both correct and incorrect trials. Positive results will allow us to develop a stronger tie between electrophysiological and behavioral data. In Aims 2-3, we will extend this approach to region CAS and dorsolateral entorhinal cortex (EC). Computational models predict that CAS neurons should generate queued representations of temporal context, and that separate populations in EC should code for temporal context and and sequences of paths from the current location. In Aim 4, we will test the hypothesis that the period of the theta rhythm can be divided into encoding and retrieval phases. In Aim 5, we will study spatial trends in receptive fields of context-sensitive neurons. In Aim 6, we will test the hypothesis that cells encoding a given temporal context (left-turn vs. right-turn trial) are spatially clustered. In Aim 7, we will stimulate selected hippocampal neurons in an attempt induce "false memories" in the DNMP task. Aim 7 is technically challenging, but if successful, provides direct evidence that manipulation of hippocampal acitivity leads to alterations in episodic-like memory. The long-term goals of the proposed work are to establish a causal relationship between hippocampal activity and behavioral performance in episodic-like tasks, and to understand more completely how memories of relevant episodic experiences are encoded in entorhinal cortex and in regions CA1 and CAS of hippocampus. Such levels of understanding will be of great value in working toward treatments for memory disorders. The value of the planned experiments is not contingent on positive results from the high-risk Aim 7.

人们认为海马对于学习序列和歧义是必要的，并且 计算模型预测海马形成的不同子区域 在内存中的独特角色。但是，这些预测尚未通过实验测试，没有人有 证明了海马活动与动物行为的活动模式之间的因果关系。 该项目将解决在“ T”中执行延迟不匹配（DNMP）任务的动物中的这两个问题 迷宫。在AIM 1中，我们将研究上下文敏感序列神经活动的出现。 动物的背侧海马学习任务，并比较样本，延迟和选择的活动 在正确和不正确试验中，任务的阶段。积极的结果将使我们能够建立更强的领带 在电生理和行为数据之间。在目标2-3中，我们将将这种方法扩展到区域CAS 和背侧内嗅皮层（EC）。计算模型预测CAS神经元 应该产生时间上下文的排队表示，并且EC中的单独人群应 时间上下文和当前位置的路径序列的代码。在AIM 4中，我们将测试 假设可以将theta节奏的周期分为编码和检索阶段。在AIM 5中， 我们将研究上下文敏感神经元接受的空间趋势。在AIM 6中，我们将测试 假设编码给定时间上下文（左转与右转试验）的细胞在空间上聚集。 在AIM 7中，我们将刺激选定的海马神经元尝试引起“虚假记忆” DNMP任务。 AIM 7在技术上具有挑战性，但如果成功，则提供了直接证据表明操纵 海马尊严会导致情节样记忆的改变。 拟议工作的长期目标是建立海马之间的因果关系 在类似情节的任务中的活动和行为表现，并更完全了解 相关情节经历的记忆在intorhinal Cortex和CA1和CAS中编码 海马。这样的理解水平将在为记忆的治疗方面致力于巨大的价值 疾病。计划实验的价值并不取决于高风险目标的积极结果 7。