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 该项目的目的是为专注于独立研究计划的构建块 跨分布式大脑网络基于奖励记忆的神经基础。人类和其他动物经历 在大脑进化出强大的神经过程以重新激活的时刻发生的事件 在“之间的时间”中编码这些事件的神经元。与任务相关的神经元集合的重新激活发生 在唤醒和睡眠状态期间，并在A中启用神经元表示的结合和压缩 临时窗口与神经元可塑性兼容。清醒和睡眠重新激活在支持中的作用 情节性，海马依赖性记忆已经确立。但是，已经报道了重新激活 还出现在海马以外的皮质和皮层结构以及海马 - 依赖和独立的任务。这导致令人兴奋的可能性，重新激活可能是基本的 记忆形成和巩固的基础机制，并且它们在脑室内发生，分布在 编码不同方式和变量的区域。但是，它们在提示驱动的，目标指导的感觉运动中的作用 任务在很大程度上仍然是出乎意料的，并且多区域重新激活的证据很弱，部分原因是技术 很难研究多个简单记录的脑电路的神经元种群活性。 该提案旨在测试唤醒过程中多区域神经元重新激活的作用 并合并关联网络以支持基于奖励的学习。在K99阶段，Drieu博士将集中精力 关于多区域重新激活在提示引导，目标指导学习中的作用。她将检验以下假设 在整个大脑区域的刺激，动作和奖励选择性神经元的简单重新激活 唤醒状态形式的联想网络（AIM 1）随后在睡眠过程中重新激活以进行整合（目标 2）。在R00阶段，Drieu博士将解决瞬时同步活动是否跨越多个大脑区域 在不同的大脑状态中，参与从提示驱动的，以中心为中心的记忆到以自我为中心的记忆的过渡 （目标3）。为了实现这些目标，Drieu博士将使用 Neuropixels 2.0与自由移动大鼠的高级闭环光遗传学方法结合在一起。技术 Drieu博士在该项目的培训期间将发展的科学技能不仅至关重要 实现她的直接科学目标，他们也将成为她将要进行的研究的支柱 在自己的独立实验室中发展基于奖励的学习和记忆领域。这个培训将 由激烈的职业发展活动和心态完成，这将为她做好准备 实验室管理，教学和筹款的实际方面。总的来说，Drieu博士的未来研究将 提供有关记忆形成所涉及的神经机制的新见解。这将为 更好地了解这些机制与与奖励相关的病理学是否出现了 诸如成瘾之类的疾病，并有记忆定义了阿尔茨海默氏病。