Subicular Contributions to Memory-Guided Decision Making

对记忆引导决策的潜意识贡献

• 批准号: 10525205
• 负责人: Jacob Michael Olson
• 金额: $ 12.15万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10525205
• 关键词: Address; Alzheimer' s Disease; Anatomy; Anxiety; Anxiety Disorders; Award; Behavior; Behavioral; Behavioral Paradigm; Brain region; Categories; Characteristics; Cognitive; Complement; Complex; Data; Decision Making; Development; Development Plans; Disease; Dorsal; Educational process of instructing; Electrophysiology (science); Emotional; Epilepsy; Etiology; Event; Exhibits; Foundations; Functional disorder; Future; Hippocampus (Brain); Individual; Insula of Reil; Interruption; Lead; Learning; Link; Location; Medial; Memory; Mental Depression; Mental disorders; Mentors; Modeling; Nature; Neurons; Neurophysiology - biologic function; Neurosciences; Output; Pathologic; Pathway interactions; Pattern; Performance; Periodicity; Phase; Physiological; Physiology; Population; Post-Traumatic Stress Disorders; Process; Property; Psychology; Pyramidal Cells; Rattus; Reader; Research; Research Personnel; Rewards; Role; Scheme; Schizophrenia; Shapes; Short-Term Memory; Signal Transduction; Techniques; Temporal Lobe; Testing; Theoretical model; Time; Training; Universities; awake; base; biomarker identification; biophysical model; cognitive ability; cognitive function; cognitive process; cognitive task; density; effective intervention; effective therapy; entorhinal cortex; experience; experimental study; hedonic; hippocampal subregions; in vivo; innovation; memory encoding; memory retrieval; neural circuit; neuromechanism; neurophysiology; novel; optogenetics; predictive modeling; programs; relating to nervous system; virtual; way finding

PROJECT SUMMARY The ability to form and store memories from experience to shape future behavior is a remarkable and foundational cognitive capability. While many brain regions interact to enable cognitive processes of learning and decision making, the subiculum and hippocampus of the medial temporal lobe are central nodes in the underlying neural circuit. Accordingly, medial temporal lobe dysfunction is a hallmark of psychiatric disorders such as depression, PTSD and other anxiety disorders, epilepsy, and Alzheimer’s disease. Understanding basic neural function and coordination processes in the subiculum and hippocampus during memory and decision making will therefore be crucial in the progress towards effective interventions for these disorders; however, subiculum function and its coordination with hippocampus during these cognitive tasks is almost completely unknown. The central hypothesis of this proposal is that subiculum links individual memories formed by the hippocampus and thereby enables cognitive capabilities such as abstraction, categorization, and deliberation during decision making. During the mentored phase (K99), high-density in vivo electrophysiology will be used in rats to observe subiculum and hippocampal subregion CA1 activity during a navigational memory-guided decision making task. Optogenetic interruption of the proposed coordination mechanism between subiculum and CA1 during behavior will then provide evidence to its necessity for memory-guided decision making. Theoretical models will assess plausible mechanisms underlying the formation of subiculum activity patterns. Experiments during the independent (R00) phase will extend this approach through the dorsal-ventral extent of CA1 and subiculum and to emotional aspects of memory such as hedonic value. Successful completion of this proposal has the potential to result in two significant conceptual breakthroughs: 1) subiculum is a major and critical component of hippocampal output with specific and distinct functions during memory-guided decision making, 2) subiculum and CA1 function and encoding properties are consistent throughout their dorsal-ventral extents and are best understood under a single conceptual framework. This research plan will be executed by Dr. Jacob Olson under the guidance of Dr. Shantanu Jadhav and Dr. Donald Katz, facilitated by the collaborative, innovative, and rigorous nature of the Neuroscience Program and Department of Psychology at Brandeis University. This proposal also contains a comprehensive training and development plan with emphases on cutting-edge recoding and manipulation techniques, theoretical modeling, and scholarly development to fully prepare Dr. Olson to lead an innovative and impactful research program studying the mechanisms of neural coordination underlying memory-guided decision making as an independent investigator.

项目概要 从经验中形成和存储记忆以塑造未来行为的能力是一种非凡的能力 基础认知能力。虽然许多大脑区域相互作用以实现学习的认知过程 和决策过程中，内侧颞叶的下托和海马是大脑中的中央节点。 底层神经回路。因此，内侧颞叶功能障碍是精神疾病的一个标志 例如抑郁症、创伤后应激障碍（PTSD）和其他焦虑症、癫痫症和阿尔茨海默病。了解基本 记忆和决策过程中下托和海马的神经功能和协调过程 因此，对于这些疾病的有效干预措施的进展至关重要；然而， 在这些认知任务中，下托功能及其与海马体的协调几乎完全 未知。该提议的中心假设是下托连接着由 海马体，从而实现抽象、分类和深思熟虑等认知能力 在决策过程中。在指导阶段（K99），高密度体内电生理学将用于 大鼠在导航记忆引导期间观察下托和海马亚区 CA1 活动 决策任务。下托和下托之间所提出的协调机制的光遗传学中断 行为过程中的 CA1 将提供证据证明其记忆引导决策的必要性。理论 模型将评估下托活动模式形成的合理机制。实验 在独立 (R00) 阶段将通过 CA1 的背腹范围扩展此方法， 下托和记忆的情感方面，例如享乐价值。圆满完成本次提案 有可能带来两个重大的概念突破：1）下托是一个主要且关键的 在记忆引导决策过程中具有特定和独特功能的海马输出的组成部分， 2) 下托和CA1的功能和编码特性在其背腹范围内是一致的 并且在单一概念框架下可以得到最好的理解。该研究计划将由雅各布博士执行 奥尔森在 Shantanu Jadhav 博士和 Donald Katz 博士的指导下，在协作的推动下， 布兰迪斯神经科学项目和心理学系的创新性和严谨性 大学。该提案还包含全面的培训和发展计划，重点是 尖端的记录和操作技术、理论建模和学术发展，以充分 准备奥尔森博士领导一项创新且有影响力的研究项目，研究神经机制 作为独立调查员，协调是记忆引导决策的基础。