Hippocampal-cortical interactions supporting memory and value-guided decision-making

海马-皮质相互作用支持记忆和价值引导决策

• 批准号: 10463588
• 负责人: Alison E. Comrie
• 金额: $ 4.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463588
• 关键词: Animals; Behavior; Brain; Cells; Complex; Decision Making; Disease; Dorsal; Environment; Evaluation; Event; Exhibits; Feedback; Food; Future; Health; Hippocampus (Brain); Impairment; Incidence; Institution; Interneurons; Investigation; Knowledge; Learning; Location; Locomotion; Memory; Mental disorders; Mentorship; Neurons; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Optics; Outcome; Pattern; Performance; Phase; Positioning Attribute; Prefrontal Cortex; Probability; Process; Psyche structure; Rattus; Recording of previous events; Research; Resources; Rewards; Role; Route; Schizophrenia; Services; Shapes; Site; Source; System; Technology; Testing; Theta Rhythm; Time; Training; Uncertainty; addiction; base; cognitive function; effective therapy; experience; experimental study; flexibility; improved; neuromechanism; prospective; relating to nervous system; simulation; spatial memory

Project Summary/Abstract Prior experiences can profoundly shape subsequent decisions. Mental simulation of potential futures based on memories of prior actions and resultant outcomes is one strategy to support making adaptive decisions. Substantial evidence demonstrates that the hippocampus (HC) is involved in this process: planning and imagining future events based on previous spatial experiences. More specifically, the HC exhibits temporally compressed sequences of neural firing that are thought to internally represent prospective locations distinct from the animal’s current place in an environment. This “nonlocal” activity may enable consideration of alternate routes during learning, when the optimal choice is unclear. In order to make a decision about which trajectory to take, however, the brain must not only internally represent potential paths, but also the expected value of each choice. Neural activity in the prefrontal cortex (PFC) can encode the value of a choice’s outcome and is modulated by reward. This evidence makes the PFC a strong candidate site for the evaluation of potential spatial choices based on reward history. Despite substantial research on the respective functions of either the HC or PFC in memory or value-guided decisions, little is known about how these circuits interact to support behavior. Coordinated neural activity across these circuits may facilitate spatial evaluation in service of adaptive decisions and may be modulated by learning. Specifically, this project tests the hypothesis that nonlocal representations in the HC are a mechanism of spatial deliberation, and that they are coordinated with PFC value representations to support reward history-guided adaptive decisions. Testing this hypothesis requires uniting approaches typically used to study either the HC and spatial memory or the PFC and decision-making. The proposed experiments therefore comprise simultaneous recordings of the HC and PFC in rats during the performance of a spatial decision-making task with changing reward contingencies (Aims 1 and 2) and closed-loop optical inactivation of the HC based on neural feedback during behavior (Aim 3). By working at the intersection of established but often separate lines of investigation on memory and decisions, the proposed Specific Aims have the potential to test prominent hypotheses and elucidate the neural underpinnings of experience-based decision processes. Furthermore, understanding the neural substrates that enable memory-guided decision-making is critical to understanding related psychiatric disorders in which HC and PFC circuits malfunction, such as addiction, obsessive-compulsive disorder, and schizophrenia. The proposed research strategy is bolstered by a training plan with experimental and analytical strength and is necessarily guided by a sponsor who is a leader in the technical and conceptual aspects of the project. The research environment is accordingly equipped with mentorship, technology, and expertise, all within UCSF, a collaborative institution dedicated to advancing health worldwide.

项目总结/摘要 先前的经验可以深刻地影响随后的决定。潜在未来的心理模拟 基于对先前行为和结果的记忆， 决策大量证据表明，海马体（HC）参与了这一过程： 并根据先前的空间经验想象未来的事件。更具体地说，HC展示了 被认为在内部代表预期位置的时间压缩的神经放电序列 与动物目前在环境中的位置不同。这一“非本地”活动可能有助于考虑 在学习过程中，当最佳选择不清楚时，选择替代路线。为了做出决定 然而，要走的轨迹，大脑不仅必须在内部代表潜在的路径，而且还必须代表预期的路径。 每个选择的价值。前额叶皮层（PFC）的神经活动可以编码选择结果的价值 并受奖励的调节。这一证据使PFC成为评估以下方面的强有力候选地点： 基于奖励历史的潜在空间选择。尽管大量的研究各自的功能， 无论是记忆中的HC或PFC，还是价值导向决策，人们对这些回路如何相互作用知之甚少， 支持行为。这些回路之间协调的神经活动可能有助于空间评估， 自适应决策，并且可以通过学习来调节。具体来说，这个项目测试的假设， HC中的非局部表征是空间审议的一种机制，它们是 与PFC值表示协调，以支持奖励历史指导的自适应决策。 检验这一假设需要联合通常用于研究HC和空间的方法。 记忆或前额叶皮层和决策。因此，所提出的实验包括同时进行的 记录的HC和PFC在大鼠的空间决策任务的性能与变化 奖励意外事件（目标1和2）和基于神经反馈的HC闭环光学失活 行为（目标3）。通过在已建立但通常独立的调查路线的交叉点工作 在记忆和决策方面，所提出的具体目标有可能检验突出的假设， 阐明基于经验的决策过程的神经基础。此外，了解 神经基质，使记忆引导决策是至关重要的理解相关的 HC和PFC回路功能障碍的精神障碍，如成瘾、强迫症 精神分裂症。拟议的研究战略得到了一个实验性的培训计划的支持， 和分析能力，并必须由一个在技术和概念方面处于领先地位的赞助商指导。 项目的各个方面。研究环境相应地配备了导师，技术， UCSF是一个致力于促进全球健康的合作机构。

项目成果

Imagination as a fundamental function of the hippocampus.

• DOI: 10.1098/rstb.2021.0336
• 发表时间: 2022-12-19
• 期刊: PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 6.3
• 作者: Comrie, Alison E.;Frank, Loren M.;Kay, Kenneth
• 通讯作者: Kay, Kenneth