Functional Role of Hippocampal Neuronal Representations

海马体被认为是学习序列和消除歧义所必需的，并且 计算模型预测，不同的海马区结构发挥作用 在记忆中扮演不同的角色。然而，这些预测还没有经过实验验证，也没有人这样做过 证明了海马体活动模式和动物行为之间的因果关系。 这个项目将解决动物在“T”中执行延迟不匹配放置(DNMP)任务时的这两个问题。 迷宫。在目标1中，我们将研究CA1区上下文相关序列神经活动的出现。 当动物学习任务时，背侧海马体，并比较样本、延迟和选择的活动 在正确和不正确的试验中任务的各个阶段。积极的结果将使我们发展更牢固的关系 电生理和行为数据之间的关系。在目标2-3中，我们将把这种方法推广到区域CAS 背外侧内嗅皮层(EC)。计算模型预测CAS神经元 应生成时间上下文排队表示，且EC中的单独种群应 用于从当前位置开始的路径的时间上下文和AND序列的代码。在目标4中，我们将测试 假设theta节律的周期可以分为编码和提取阶段。在《目标5》中， 我们将研究上下文敏感神经元感受野的空间趋势。在目标6中，我们将测试 假设编码给定时间背景的细胞(左转与右转试验)在空间上是聚集的。 在目标7中，我们将刺激选定的海马神经元，试图在 DNMP任务。AIM 7在技术上具有挑战性，但如果成功，它提供了直接证据表明操纵 海马区的活动导致情景样记忆的改变。 这项拟议工作的长期目标是建立海马区之间的因果关系 在类似情景的任务中的活动和行为表现，并更全面地了解如何 相关情节经验的记忆编码在内嗅皮层以及大脑中脑区的CA1和CAS。 海马体。这样的理解水平将对致力于治疗记忆具有重大价值。 精神错乱。计划中的实验的价值不取决于高风险目标的积极结果 7.

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.