The role of hippocampal sequence play in learning and decision making

海马序列在学习和决策中的作用

• 批准号: 7984101
• 负责人: David J Foster
• 金额: $ 41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7984101
• 关键词: Address; Aging; Alzheimer' s Disease; Animals; Area; Autistic Disorder; Behavior; Behavioral; Brain; Brain Diseases; Brain region; Cells; Cognition; Data; Decision Making; Development; Disease; Electroencephalography; Electrophysiology (science); Epilepsy; Episodic memory; Event; Exhibits; Future; Goals; Hippocampus (Brain); Learning; Light; Link; Location; Medial; Medicine; Memory; Memory Disorders; Modeling; Neurons; Outcome; Pattern; Performance; Play; Population Study; Prefrontal Cortex; Prevalence; Process; Publications; Rattus; Recruitment Activity; Research; Retrieval; Rewards; Role; Running; Schizophrenia; Sleep; Staging; Stroke; Syndrome; Techniques; Technology; Temporal Lobe Epilepsy; Testing; Time; Training; awake; base; behavior influence; density; experience; follow-up; insight; memory process; memory retrieval; normal aging; novel; prospective; public health relevance; relating to nervous system; research study; response; spatiotemporal; therapeutic target

DESCRIPTION (provided by applicant): We aim to study how populations of neurons in the hippocampus and prefrontal cortex support navigational learning and decision-making. During awake behavior, hippocampal neurons are active in precise sequences that reflect trajectories taken in the past, and hypothetical trajectories to be taken in the future. This phenomenon is known as awake replay. The broad objective of this proposal is to investigate a possible role for awake replay in learning and decision making. Previous data together with a model suggest a framework in which replay sequences can be used to learn trajectories to reward locations, and also provide the ability to "look ahead" along hypothetical future trajectories during decision-making. We make use of high-density tetrode electrophysiology techniques which allow simultaneous recording of hundreds of neurons in multiple brain regions, in freely behaving animals. We record single unit and wideband EEG activity during the learning and performance of navigational tasks. Our preliminary data show that replay undergoes learning-related changes, that replay in the hippocampus is closely coordinated with activity in prefrontal cortex which is an area strongly associated with decision-making, and that replay at choice points is predictive of navigational decisions. We will pursue these preliminary results in three specific aims. Understanding how replay relates to learning will provide novel insight into offline mechanisms of learning, which are increasingly thought to be important, both in normal cognition, and in diseases such as Alzheimer's disease, autism and schizophrenia. Understanding how the hippocampus interacts with prefrontal cortex during replay will shed further light on the importance of offline activity, and also provide novel insight into the way that the hippocampus conveys specific information to areas of the brain that influence behavior. Hence, we will investigate a novel and important link between hippocampal neural activity and behavioral outcomes. Finally, understanding how hippocampal replay is organized during decision-making will provide novel insight into hippocampal memory retrieval. Understanding how the hippocampus supports memory is a major goal in medicine, given the involvement of the hippocampus in memory problems in Alzheimer's disease, Korskoff's syndrome, normal aging, stroke and temporal lobe epilepsy. Further, this study may reveal novel prefrontal mechanisms of planning and decision making, which may shed light on those brain diseases that have been associated with degraded prefrontal function, such as schizophrenia and autism. Ultimately, the search for the neural basis of memory is a fundamental goal with profound implications for the development of therapeutic targets in brain disease. PUBLIC HEALTH RELEVANCE: Despite the prevalence of memory disorders associated with damage to the hippocampus, from such conditions as Alzheimer's disease, aging, stroke and epilepsy, we lack a mechanistic understanding of how hippocampal neurons encode and retrieve memories, which could help us address these problems. However, recently developed techniques for recording from large numbers of neurons simultaneously in awake, freely behaving animals, have begun to reveal patterns of activity across hippocampal neurons that may provide a model of memory processing. This study will take these results further by asking how the retrieval of specific memories by the hippocampus drives the selection of appropriate behavior, thus shining light on the very processes that may go awry when memory fails.

描述（由申请人提供）：我们的目标是研究海马体和前额皮质中的神经元群体如何支持导航学习和决策。在清醒行为期间，海马神经元以精确的序列活跃，这些序列反映了过去采取的轨迹以及未来采取的假设轨迹。这种现象称为唤醒重放。该提案的主要目标是研究清醒重放在学习和决策中可能发挥的作用。先前的数据与模型一起提出了一个框架，其中重放序列可用于学习奖励位置的轨迹，并且还提供在决策过程中沿着假设的未来轨迹“展望”的能力。我们利用高密度四极电生理学技术，可以同时记录自由行为动物多个大脑区域的数百个神经元。我们在学习和执行导航任务期间记录单单位和宽带脑电图活动。我们的初步数据表明，重放经历了与学习相关的变化，海马体中的重放与前额皮质的活动密切协调，前额皮质是与决策密切相关的区域，并且选择点的重放可以预测导航决策。我们将在三个具体目标上追求这些初步成果。了解重播与学习的关系将为离线学习机制提供新的见解，人们越来越认为离线学习机制对于正常认知以及阿尔茨海默病、自闭症和精神分裂症等疾病都很重要。了解海马体在回放过程中如何与前额叶皮层相互作用，将进一步阐明离线活动的重要性，并为海马体向影响行为的大脑区域传递特定信息的方式提供新的见解。因此，我们将研究海马神经活动与行为结果之间的新颖且重要的联系。最后，了解海马体重放在决策过程中是如何组织的将为海马体记忆检索提供新的见解。鉴于海马体与阿尔茨海默病、科尔斯科夫综合征、正常衰老、中风和颞叶癫痫等记忆问题有关，了解海马体如何支持记忆是医学的一个主要目标。此外，这项研究可能揭示新的规划和决策的前额叶机制，这可能有助于揭示那些与前额叶功能退化相关的脑部疾病，例如精神分裂症和自闭症。最终，寻找记忆的神经基础是一个基本目标，对脑部疾病治疗靶点的开发具有深远的影响。 公共健康相关性：尽管与海马体损伤相关的记忆障碍普遍存在，例如阿尔茨海默病、衰老、中风和癫痫等，但我们对海马神经元如何编码和检索记忆缺乏机制性的了解，而这可以帮助我们解决这些问题。然而，最近开发的在清醒、自由行为的动物中同时记录大量神经元的技术已经开始揭示海马神经元的活动模式，这可能提供记忆处理的模型。这项研究将通过询问海马体对特定记忆的检索如何驱动适当行为的选择来进一步研究这些结果，从而揭示记忆失败时可能出错的过程。