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.

项目摘要 该项目的目标是为一个独立的研究计划提供基础， 基于奖励的记忆的神经基础。人类和其他动物经历 事件发生时，大脑已经进化出强大的神经过程来重新激活大脑 神经元在“时间间隔”中编码这些事件。任务相关神经元集合的再激活发生 在清醒和睡眠状态下，并使神经元表示的绑定和压缩， 与神经元可塑性相容的时间窗。清醒和睡眠再激活在支持 情节性的、依赖于校园的记忆已经很好地建立起来。然而，据报道， 也发生在海马体之外，在皮质和皮质下结构中，以及在海马体和海马体中， 独立和非独立任务。这导致了一个令人兴奋的可能性，即重新激活可能是一个基本的 记忆形成和巩固的机制，它们发生在全脑，分布在 编码不同模态和变量的区域。然而，它们在线索驱动、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很弱，部分原因是技术原因， 难以在多个同时记录的脑回路中研究神经元群体活动。 该建议旨在测试清醒和睡眠期间多区域神经元再激活在形成脑内神经元的作用。 以及巩固关联网络以支持基于奖励的学习。在K99阶段，Dr. Drieu将专注于 多区域再激活在线索引导、目标导向学习中的作用。她将检验一个假设， 刺激，动作和奖励选择神经元在大脑区域的同时重新激活， 清醒状态形成联想网络（Aim 1），随后在睡眠期间重新激活以进行巩固（Aim 2）。在R00阶段，Drieu博士将讨论是否跨越多个大脑区域的瞬时同步活动 在不同的大脑状态下，参与了从线索驱动的、以自我为中心的记忆到以自我为中心的记忆的转变 (Aim 3）。为了实现这些目标，Dr. Drieu将使用 Neuropixels 2.0结合先进的闭环光遗传学方法在自由活动大鼠中的应用。技术 Drieu博士将在该项目的培训期间开发的科学技能不仅对 她的直接科学目标的实现，他们也将成为研究的支柱，她将 在她自己的独立实验室里，她在奖励性学习和记忆领域进行了研究。本次培训将 辅之以密集的职业发展活动和指导，这将为她准备 实验室管理、教学和资金筹措等方面的实践。总的来说，Dr. Drieu未来的研究将 为记忆形成的神经机制提供了新的见解。这将奠定基础， 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。