Cognitive maps and novel behavioral sequences in the hippocampus

海马体的认知图和新颖的行为序列

• 批准号: 7997101
• 负责人: Anoopum Satyawan Gupta
• 金额: $ 4.64万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7997101
• 关键词: Affect; Alzheimer' s Disease; Animals; Behavior; Behavioral; Biological Models; Cognition; Cognitive; Decision Making; Disease; Electrodes; Environment; Episodic memory; Family; Functional disorder; Hippocampus (Brain); Imagination; Individual; Knowledge; Learning; Location; Maps; Memory; Modeling; Outcome; Patients; Personality; Phase; Play; Population; Process; Pyramidal Cells; Rodent; Role; Running; Schizophrenia; Structure; Testing; Time; addiction; awake; base; cognitive function; experience; long term memory; nervous system disorder; neuromechanism; novel; public health relevance; relating to nervous system; research study; way finding

DESCRIPTION (provided by applicant): Many of the most debilitating neurological disorders, including Alzheimer's disease, schizophrenia, and addiction, drastically affect cognitive function. Functions such as episodic memory and decision-making define an individual's personality and the decline of these functions is debilitating to patients and families. To develop directed therapies to treat deficits in cognitive function, we must understand the neural mechanisms supporting normal cognition. The hippocampus is known to play an important role in episodic memory and spatial navigation, and has recently been implicated in self-projection and imagination. The rodent hippocampus has been an extremely informative model system because it is relatively easy to access with electrodes, and because the firing of hippocampal pyramidal cells has a clear behavioral correlate: the animal's location in an environment. At any given time as an animal moves through an environment, the population of pyramidal cells in the hippocampus is representing the animal's physical location. At choice points in a maze, as an animal demonstrates tentative behaviors suggestive of considering its options, the hippocampal representation of location sweeps forward from the animal's current location down the possible paths it might take. This has been hypothesized to be a mechanism for evaluating the outcome of potential choices. At other times, while the animal is paused and inattentive but awake, the hippocampus replays sequences of neural activity representing behavioral experiences in the order they were experienced (forward replay) and in the reverse order that they were experienced (backward replay). The neural mechanisms supporting backward replay are currently unknown. Replay is thought to be important for consolidating recent memories into long-term memory and for learning general knowledge structures (i.e. cognitive maps) of the environment. In this proposal we investigate the neural basis of the environmental representation maintained by the hippocampus, which enables it to flexibly represent trajectories across the environment. In Specific Aim 1, we will run an experiment to investigate the ability of the hippocampus to represent behavioral sequences across a portion of the environment that was never experienced, thereby testing whether hippocampal representations are driven purely by experience. In Specific Aim 2, we will model the hippocampus to test the hypothesis that a recently discovered theta phase gradient across the hippocampus can be exploited to learn behavioral sequences in the backward order. PUBLIC HEALTH RELEVANCE: This proposal aims to further our understanding of the neural mechanisms underlying cognitive processes supported by the hippocampus, which include episodic memory, spatial navigation, and potentially imagination and self-projection. Disorders involving these cognitive processes are widespread (e.g. Alzheimer's disease and schizophrenia) and deeply affect patients and their families. Studying cognition at the neural level is important for understanding the pathophysiology of these disorders and for developing directed therapies to treat them.

描述（由申请人提供）：许多最衰弱的神经系统疾病，包括阿尔茨海默病，精神分裂症和成瘾，严重影响认知功能。情景记忆和决策等功能定义了一个人的个性，这些功能的下降会使患者和家庭衰弱。为了开发定向疗法来治疗认知功能缺陷，我们必须了解支持正常认知的神经机制。 海马体在情景记忆和空间导航中起着重要作用，最近被认为与自我投射和想象有关。啮齿类动物的海马是一个信息量非常大的模型系统，因为它相对容易用电极接近，而且海马锥体细胞的放电与动物在环境中的位置有明确的行为相关性。在任何给定的时间，当动物在环境中移动时，海马体中的锥体细胞群代表了动物的物理位置。 在迷宫中的选择点，当动物表现出考虑其选择的试探性行为时，海马体的位置表示从动物当前的位置向前扫过它可能采取的路径。这被假设为一种评估潜在选择结果的机制。在其他时候，当动物暂停和疏忽但清醒时，海马体会以经历的顺序（正向重放）和经历的相反顺序（反向重放）重放代表行为体验的神经活动序列。支持向后重放的神经机制目前尚不清楚。重播被认为是重要的巩固近期记忆到长期记忆和学习一般知识结构（即认知地图）的环境。 在这个建议中，我们调查的海马，这使它能够灵活地代表整个环境的轨迹保持的环境表示的神经基础。在具体目标1中，我们将进行一项实验，以研究海马体在从未经历过的环境中表征行为序列的能力，从而测试海马体表征是否纯粹由经验驱动。在具体目标2中，我们将对海马体进行建模，以检验一个假设，即最近发现的海马体中的θ相位梯度可以用来以向后的顺序学习行为序列。 公共卫生相关性：该提议旨在进一步了解海马支持的认知过程的神经机制，包括情景记忆，空间导航，以及潜在的想象力和自我投射。涉及这些认知过程的障碍很普遍（例如阿尔茨海默病和精神分裂症），并深深影响患者及其家人。在神经水平上研究认知对于理解这些疾病的病理生理学和开发治疗它们的定向疗法是重要的。