Hippocampal-prefrontal interactions underlying learning and memory

海马-前额叶相互作用是学习和记忆的基础

• 批准号: 8864434
• 负责人: Shantanu P Jadhav
• 金额: $ 24.9万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8864434
• 关键词: Address; Affect; Animals; Anxiety; Behavior; Brain; Brain region; Clinic; Clinical; Cognition; Cognitive; Communication; Complex; Data Analyses; Decision Making; Detection; Development; Disease; Educational process of instructing; Educational workshop; Environment; Functional disorder; Funding; Goals; Grant; High Frequency Oscillation; Hippocampus (Brain); Investigation; Knowledge; Learning; Light; Link; Marketing; Medial; Mediating; Memory; Mental Depression; Mental disorders; Mentors; Mentorship; Nature; Nervous system structure; Neurons; Occupations; Pattern; Performance; Phase; Physiological; Physiology; Play; Positioning Attribute; Post-Traumatic Stress Disorders; Postdoctoral Fellow; Prefrontal Cortex; Process; Research; Research Personnel; Resources; Retrieval; Rodent; Role; Schizophrenia; Short-Term Memory; Site; Sleep; Slow-Wave Sleep; Structure; Techniques; Testing; Time; Training; Work; Writing; abstracting; awake; base; behavioral impairment; career; career development; cognitive function; effective therapy; experience; frontal lobe; improved; interest; memory process; neural patterning; neuronal patterning; neurophysiology; novel; optogenetics; professor; relating to nervous system; research study; skills; symposium

Project Summary / Abstract Research The ability to form memories and use past experience to guide behavior is one of the most remarkable capacities of the nervous system. Multiple brain regions interact with each other to support the complex cognitive processes of learning and decision-making, and the hippocampus and medial prefrontal cortex (PFC) play important roles in these processes. The hippocampus is necessary for rapid episodic learning and memory, while PFC is crucial for memory consolidation and retrieval, and for cognitive functions like decision- making and working memory. How these structures interact with each other to support behavior is still poorly understood. Further, neural activity in the hippocampus and PFC is implicated in numerous psychiatric disorders, including PTSD, depression, anxiety and schizophrenia. My long-term goal is to understand the physiological bases of hippocampal-prefrontal interactions during behavior, and dysfunction in these processes in pathological states. The objective of this proposal is to investigate the nature and role of hippocampal-PFC interactions mediated by a particular neural pattern of activity, awake sharp wave ripples (SWRs), in learning and memory-guided decision making. First, I will use multisite multielectrode recordings in the hippocampus and PFC in awake behaving animals during learning to test the hypothesis that memory replay in the hippocampus during awake SWRs activates mnemonic patterns in PFC. Second, I will take advantage of a novel technique for real-time detection and disruption of awake SWRs to investigate if awake SWRs are required for formation of stable memory patterns in PFC. Finally, I will determine the causal role of hippocampal-PFC interactions during awake SWRs in memory-guided decision making by using optogenetic inhibition of PFC activity contingent on real-time detection of awake SWRs during behavior. These experiments will advance our understanding of propagation of mnemonic activity between the hippocampus and PFC and provide direct and causal evidence linking physiological phenomena to behavior. Candidate My broad interests are in understanding the neurophysiological basis of behavior. My long-term goal is to become an independent investigator with a lab that focuses on investigating how different brain structures interact with each other to support complex cognitive processes such as learning and decision-making, and understanding how dysfunction in these processes leads to pathological states in disease. I want to use a combination of techniques, including electrophysiological recordings in behaving animals, real-time detection and manipulation of physiological patterns, and perturbation of neural activity in specific circuits during behavior, to determine causal links between physiological phenomena and behavior. During the training phase of this application, I will gain additional skills in conceptual, technical and career development aspects which will enable me to make a successful transition to an independent position with my own research group. My short-term goals are, 1) to improve my knowledge about pre-frontal cortex (PFC) physiology and to gain expertise in multi-site recordings in the hippocampus and PFC, 2) to acquire further proficiency in data analyses skills, 3) to gain expertise in simultaneous optogenetic manipulations and physiology in awake- behaving rodents, 4) to improve my knowledge in the clinical aspects of my research, 5) to obtain an independent tenure-track assistant professor position and transfer to the R00 portion of this proposal within 2 years, and 6) to successfully obtain R01 funding within 5 years of this proposal. Environment • The vibrant, collaborative research environment at UCSF is conducive to the attainment of these goals. My co-mentors and consultants have extensive experience in prefrontal physiology and optogenetics, and also in the pathophysiology of hippocampal and prefrontal disorders. Through my co-mentorship and consultants, I also have access to UCSF's Ernest Gallo Clinic and Research Center, which will aid in these research goals. • UCSF also offers academic courses that I will utilize to gain these research skills. UCSF provides a number of career development resources to help postdoctoral fellows gain additional skills required to achieve independence, which include seminars and classes aimed at preparing postdocs for the academic job market and a dedicated resource that helps postdocs apply for academic jobs. I will utilize all these resources to enhance my career skills. • I will present my scientific work in conferences and regularly in departmental seminars. I will also attend grant writing, lab management and teaching workshops offered at UCSF.

项目总结/摘要 研究 形成记忆和利用过去的经验来指导行为的能力是最显著的能力之一 神经系统的能力。多个大脑区域相互作用以支持复合体 学习和决策的认知过程，以及海马和内侧前额叶皮层（PFC） 在这些过程中发挥重要作用。海马体是快速情景学习所必需的， 记忆，而PFC是至关重要的记忆巩固和检索，并为认知功能，如决策， 记忆和工作记忆。这些结构如何相互作用以支持行为仍然很差 明白此外，海马体和PFC中的神经活动与许多精神疾病有关。 包括创伤后应激障碍、抑郁症、焦虑症和精神分裂症。我的长期目标是了解 行为过程中大脑前额叶-大脑前额叶相互作用的生理基础，以及这些过程中的功能障碍 处于病态状态本提案的目的是调查前额叶皮层的性质和作用 在学习过程中，由特定的神经活动模式（清醒时的尖波波纹（SWRs））介导的相互作用 和记忆引导的决策。首先，我将在海马体中使用多点多电极记录， 和PFC在清醒行为的动物在学习过程中，以测试的假设，记忆重放在 在清醒状态下，海马体激活PFC中的记忆模式。其次，我将利用一个 一种新的技术，用于实时检测和中断唤醒的SWR，以调查唤醒的SWR是否被 在PFC中形成稳定的记忆模式所需的。最后，我将确定 使用光遗传学研究记忆引导决策中清醒状态下SWRs期间的脑-PFC相互作用 PFC活性的抑制取决于行为期间清醒SWR的实时检测。这些实验 将促进我们对海马体和PFC之间记忆活动传播的理解， 提供直接和因果关系的证据，将生理现象与行为联系起来。 候选 我的广泛兴趣在于理解行为的神经生理学基础。我的长期目标是 成为一名独立的调查员，拥有一个专注于研究不同大脑结构 相互作用，以支持复杂的认知过程，如学习和决策， 了解这些过程中的功能障碍如何导致疾病的病理状态。我想用一个 技术的组合，包括行为动物的电生理记录，实时检测 生理模式的操纵，以及特定回路中神经活动的扰动， 行为，以确定生理现象和行为之间的因果关系。在训练阶段期间 通过这次申请，我将获得在概念，技术和职业发展方面的额外技能， 将使我能够成功地过渡到一个独立的位置与我自己的研究小组。我 短期目标是，1）提高我对前额叶皮层（PFC）生理学的知识， 在海马和PFC的多站点记录的专业知识，2）获得进一步的数据熟练 分析技能，3）获得在清醒状态下同时进行光遗传学操作和生理学的专业知识， 行为啮齿动物，4）提高我在临床方面的知识，我的研究，5）获得一个 独立的终身助理教授职位，并在2年内转移到R 00部分 6）在本提案提出后的5年内成功获得R 01资金。 环境 UCSF充满活力的合作研究环境有利于实现这些目标。我 共同导师和顾问在前额叶生理学和光遗传学方面拥有丰富的经验， 海马体和前额叶疾病的病理生理学。通过我的共同指导和顾问， 我还可以访问加州大学旧金山分校的欧内斯特加洛诊所和研究中心，这将有助于这些研究 目标. · UCSF还提供学术课程，我将利用这些课程来获得这些研究技能。UCSF提供了一个数字 的职业发展资源，以帮助博士后获得所需的额外技能，以实现 独立性，其中包括旨在为学术工作做准备的研讨会和课程 市场和专门的资源，帮助博士后申请学术工作。我会利用这些 提高我的职业技能。 ·我将在会议上和定期在部门研讨会上介绍我的科学工作。我也会出席 拨款写作，实验室管理和教学研讨会在加州大学旧金山分校提供。