Role of multi-regional neuronal reactivations in reward-based memories

多区域神经元再激活在基于奖励的记忆中的作用

• 批准号: 10722635
• 负责人: celine Drieu
• 金额: $ 12.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722635
• 关键词: Address; Alzheimer' s Disease; Animals; Area; Auditory; Auditory area; Binding; Brain; Brain Diseases; Brain region; Cells; Complement; Complex; Corpus striatum structure; Cues; Detection; Development; Disease; Dorsal; Educational process of instructing; Environment; Episodic memory; Event; Exhibits; Fire - disasters; Fund Raising; Goals; Hippocampus; Human; Laboratories; Learning; Left; Location; Measures; Medial; Memory; Memory impairment; Mentors; Mentorship; Methods; Modality; Motivation; Neuronal Plasticity; Neurons; Outcome; Pathology; Pattern; Performance; Phase; Physiological; Play; Population; Prefrontal Cortex; Process; Radial; Rattus; Reporting; Research; Response to stimulus physiology; Rest; Retrieval; Rewards; Role; Sensory; Site; Sleep; Stimulus; Structure; System; Testing; Time; Training; Work; addiction; arm; awake; career; cell assembly; density; experience; in vivo; insight; learning outcome; memory consolidation; memory encoding; memory process; neural; neural patterning; neuromechanism; neurophysiology; optogenetics; programs; response; skills; spatial memory; support network

PROJECT SUMMARY The goal of this project is to provide the building blocks for an independent research program focused on the neural basis of reward-based memory across distributed brain networks. Humans and other animals experience events in the moments they occur while the brain has evolved powerful neural processes to re-activate the neurons encoding these events in the ‘time in-between’. Reactivation of task-relevant neuronal ensembles occur during both wake and sleep states, and enable the binding and compression of neuronal representations in a temporal window compatible with neuronal plasticity. The role of awake and sleep reactivations in supporting episodic, hippocampus-dependent memories is well established. However, reactivation have been reported to also occur beyond the hippocampus, in both cortical and subcortical structures, and in both hippocampal- dependent and -independent tasks. This leads to the exciting possibility that reactivations may be a fundamental mechanism underlying memory formation and consolidation, and that they occur brain-wide, distributed among regions encoding different modalities and variables. However, their role in cue-driven, goal-directed sensorimotor tasks remain largely unexplored and evidence of multiregional reactivations is weak, in part because of technical difficulty to investigate neuronal population activity across multiple simultaneously recorded brain circuits. This proposal aims at testing the role of multi-region neuronal reactivations during wake and sleep in forming and consolidating associative networks to support reward-based learning. In the K99 phase, Dr. Drieu will focus on the role of multi-regional reactivation in cue-guided, goal-directed learning. She will test the hypothesis that the simultaneous reactivation of stimulus-, action-, and reward-selective neurons across brain regions during the waking state forms associative networks (Aim 1) subsequently reactivated during sleep for consolidation (Aim 2). In the R00 phase, Dr. Drieu will address whether transient synchronous activity spanning multiple brain areas in different brain states participate in the transition from cue-driven, allocentric memories to egocentric memories (Aim 3). To achieve these goals, Dr. Drieu will perform high-density, multi-site neuronal recordings using Neuropixels 2.0 combined with advanced closed-loop optogenetic methods in freely moving rats. The technical and scientific skills that Dr. Drieu will develop during the training period of this project will not only be crucial for the accomplishment of her immediate scientific goals, they will also become the pillars for the research she will develop in her own independent laboratory in the field of reward-based learning and memory. This training will be complemented by intense career developmental activities and mentorship that will prepare her for the practical aspects of laboratory management, teaching and fund raising. Overall, Dr. Drieu’s future research will provide new insights into the neural mechanisms involved in memory formation. This will lay the groundwork to better understand whether and how these mechanisms go awry in pathologies associated with reward-related disorders such as addiction, and with memory deficits such as Alzheimer’s disease.

项目概要 该项目的目标是为专注于以下方面的独立研究计划提供构建模块： 分布式大脑网络中基于奖励的记忆的神经基础。人类和其他动物的经历 事件发生的那一刻，大脑已经进化出强大的神经过程来重新激活 神经元在“中间时间”编码这些事件。与任务相关的神经元群重新激活 在唤醒和睡眠状态下，并启用神经元表征的绑定和压缩 颞窗与神经元可塑性兼容。清醒和睡眠再激活在支持中的作用 情景性的、依赖于海马体的记忆是很成熟的。然而，据报道，重新启动 也发生在海马体以外的皮质和皮质下结构中，以及海马体中 相关任务和独立任务。这带来了令人兴奋的可能性，即重新激活可能是一个基本的 记忆形成和巩固的机制，并且它们发生在全脑范围内，分布在 编码不同模式和变量的区域。然而，它们在提示驱动、目标导向的感觉运动中的作用 任务在很大程度上尚未探索，多区域重新启动的证据薄弱，部分原因是技术问题 很难研究跨多个同时记录的大脑回路的神经元群体活动。 该提案旨在测试清醒和睡眠期间多区域神经元重新激活在形成中的作用 巩固联想网络以支持基于奖励的学习。在K99阶段，Drieu博士将重点关注 关于多区域重新激活在线索引导、目标导向学习中的作用。她将检验以下假设： 在整个大脑区域的刺激选择性、动作选择性和奖赏选择性神经元同时重新激活 清醒状态形成联想网络（目标 1），随后在睡眠期间重新激活以进行巩固（目标 2）。在R00阶段，Drieu博士将解决是否跨越多个大脑区域的瞬时同步活动 不同的大脑状态参与从线索驱动的异中心记忆到自我中心记忆的转变 （目标 3）。为了实现这些目标，Drieu 博士将使用 Neuropixels 2.0 与自由移动大鼠的先进闭环光遗传学方法相结合。技术方面 德里厄博士在该项目培训期间培养的科学技能不仅对于 在实现她眼前的科学目标的同时，这些目标也将成为她将要进行的研究的支柱 在她自己的独立实验室中，在基于奖励的学习和记忆领域进行开发。此次培训将 并辅以密集的职业发展活动和指导，为她的未来做好准备 实验室管理、教学和资金筹集的实际方面。总体而言，Drieu 博士未来的研究将 为记忆形成中涉及的神经机制提供了新的见解。这将为 更好地了解这些机制是否以及如何在与奖励相关的病理学中出错 成瘾等疾病，以及阿尔茨海默病等记忆缺陷。