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.

项目总结 这个项目的目标是为一个独立的研究项目提供基础，该项目专注于 分布式大脑网络中基于奖励的记忆的神经基础。人类和其他动物经历 当大脑进化出强大的神经过程来重新激活 神经元在“中间时间”对这些事件进行编码。与任务相关的神经元群重新激活 在觉醒和睡眠状态下，并允许绑定和压缩 与神经元可塑性相适应的时间窗。清醒和睡眠重新激活在支持中的作用 依赖于海马体的间歇性记忆已经很好地建立起来了。然而，据报道，重新激活 也发生在海马体以外，在皮质和皮质下结构中，在两个海马区- 从属和独立的任务。这导致了一种令人兴奋的可能性，即重新激活可能是 记忆形成和巩固的潜在机制，以及它们发生在整个大脑中，分布在 编码不同形态和变量的区域。然而，它们在线索驱动的、目标导向的感觉运动中的作用 任务在很大程度上仍未得到探索，多区域重新激活的证据也很弱，部分原因是技术上的 很难研究同时记录的多个大脑回路上的神经元群体活动。 这项建议旨在测试清醒和睡眠中多区域神经元重新激活在形成过程中的作用。 以及整合联想网络，以支持基于奖励的学习。在K99阶段，德里尤博士将专注于 论多区域再激活在线索引导、目标导向学习中的作用。她将检验这一假设 大脑各区域刺激、动作和奖赏选择神经元的同时重新激活 唤醒状态形成关联网络(目标1)，随后在睡眠期间重新激活以进行整合(目标1 2)。在R00阶段，Drieu博士将讨论跨多个脑区的瞬时同步活动 不同的大脑状态参与了从线索驱动的分配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，德里欧博士将使用以下技术进行高密度、多部位神经元记录 神经像素2.0结合先进的闭环光遗传方法在自由活动的大鼠中的应用。技术上的 德里尤博士将在该项目的培训期间培养的科学技能不仅对 实现她眼前的科学目标，这些目标也将成为她研究的支柱 在她自己的独立实验室里开发了基于奖励的学习和记忆领域。这次培训将 与之相辅相成的是紧张的职业发展活动和指导，这将使她为 实验室管理、教学和资金筹集的实际方面。总体而言，德里欧博士未来的研究将 提供有关记忆形成的神经机制的新见解。这将为以下工作奠定基础 更好地了解这些机制是否以及如何在与奖励相关的病理中出错 如成瘾等障碍，以及阿尔茨海默病等记忆缺陷。