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

基本信息

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
项目类别：
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&apos 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

项目摘要

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：人类和其他动物分布式大脑网络中基于奖励的记忆的神经基础。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编码这些事件的神经元在“中间时间”发生重新激活。在唤醒和睡眠状态下，并启用神经表征的绑定和压缩与神经可塑性兼容的时间窗口。清醒和睡眠再激活在支持中的作用。情景性的、海马依赖性的记忆已被很好地建立起来，然而，据报道，记忆的重新激活会导致这种记忆的发生。也发生在海马体以外的皮质和皮质下结构中，以及海马体中这导致了令人兴奋的可能性，即重新激活可能是一个基本的任务。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。任务在很大程度上仍未得到探索，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群体活动。该提案旨在测试清醒和睡眠期间多区域神经再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。她将检验多区域重新激活在线索引导、目标导向学习中的作用。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博士将解决瞬时同步活动是否跨越多个大脑区域的问题。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 博士将使用高密度、多部位神经记录。 Neuropixels 2.0 在自由移动的大鼠中结合了先进的闭环光遗传学方法。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该培训将在她自己的独立实验室中进行基于奖励的学习和记忆领域的开发。并辅以密集的职业发展活动和指导，为她的未来做好准备总体而言，Drieu 博士未来的研究将涉及实验室管理、教学和资金筹集的实际方面。提供有关记忆形成的神经机制的新见解，这将为以下方面奠定基础。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。