Segmentation and integration of experience in hippocampal neuronal representations

海马神经元表征经验的分割和整合

基本信息

批准号：
10826524
负责人：
Rachel Sophia Wahlberg
金额：
$ 5.02万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2023-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10826524
关键词：
Affect Animals Attention Brain Categories Cells Collaborations Color Complex Computing Methodologies Decision Making Electrophysiology (science)Environment Episodic memory Event Experimental Designs Female Fire - disasters Functional Magnetic Resonance Imaging Future Hippocampus Human Learning Liquid substance Location Maps Measures Memory Michigan Movement Nature Neurons Neurosciences Pattern Perception Performance Phase Play Population Positioning Attribute Process Property Rattus Research Personnel Resolution Rest Rewards Rodent Role Running Side Site Sorting Stimulus Techniques Terminator Regions Testing Time Universities awake design environmental change experience falls in vivo insight male memory consolidation memory retrieval neural neural circuit neuroimaging neuromechanism novel place fields programs segregation success theories

项目摘要

An episodic memory is a set of moments recalled together; these moments often share a unique combination of time, location, and content. Despite our experience with memories as falling into these segmented categories, it is not well-understood how the brain categorizes moments into episodes. It is theorized that the hippocampus responds to event boundaries in the environment – specific stimuli, changes in location or time, that trigger movement into the next represented episode. In humans, room boundaries and task changes are two candidate event boundaries that seem to separate distinct episodes, demonstrated by decreased memory performance across these boundaries.1 Despite the importance of episodic memory to our everyday experiences, the neural mechanisms underlying attention to event boundaries is not well understood due to resolution limitations of fMRI. Rodents provide a window into these potential neural mechanisms of event boundaries through large scale in vivo electrophysiology recordings of single neurons and local field potentials (LFP) in the hippocampus. The hippocampus is known to play a role in episodic memory consolidation and retrieval, as well as in planning and learning. Planning and episodic memory retrieval appear to have similar mechanisms displayed through replay of place cell sequences representing the track both in moments preceding and following a run during sharp-wave ripples (SWRs), transient bursts of activity in the 150-250 Hz LFP band.2 Place cell sequences matching possibilities of the rat's upcoming trajectory also often occur during theta (5-12Hz) LFP oscillations,3 a phenomenon termed “theta sequences.” Assessing how the brain represents upcoming runs during theta and SWRs, alongside determining how it replays past runs during SWRs, together brings us closer to understanding how the brain forms specific episodes. Importantly, reward locations and environmental changes have been shown to modulate hippocampal place cells and LFPs. We and others4-5 theorize that these landmarks and content shifts in rodent tasks act in a similar way to event boundaries in human episodic memory. The proposed study introduces a novel experimental design to test two candidate event boundaries in the rat, reward locations and task rule transitions paired to separately colored sides of the maze. Aim 1 will focus on discerning how hippocampal place cells and theta sequences represent space between pairs of reward locations and at environmental boundary transitions, and specifically how these representations change upon introduction of new and conflicting reward locations. Aim 2 will focus on awake SWR replays, also focusing on how segments between reward locations are represented and how these representations are together integrated with newly introduced reward locations. Completion of this proposed project will provide important insight into the neural mechanisms underlying episodic memory. This project will provide rigorous practice in experimental and computational methods and will take place in Kamran Diba's Neural Circuits and Memory lab as part of the Neuroscience Graduate Program at the University of Michigan.

情节记忆是一组偶然的时刻。这些时刻通常有独特的组合时间，位置和内容。尽管我们对记忆的经验是陷入这些细分的经验类别，这并不是很好地理解大脑类别是如何分解为情节的。理论上是海马对环境中事件边界的响应 - 特定的刺激，位置或时间的变化，这会触发运动进入下一个代表的情节。在人类中，房间边界和任务更改是两个候选事件边界似乎可以分开不同的情节，记忆力减少证明在这些边界之间的性能。1尽管情节记忆对我们每天都有重要的意义经验，关注事件界限的神经机制尚未得到很好的理解 fMRI的分辨率限制。啮齿动物为这些可能事件的神经机制提供了一个窗口通过大规模的单个神经元和局部场电位的体内电生理记录的边界（LFP）在海马中。众所周知，海马在情节记忆巩固和检索以及计划和学习。计划和情节记忆检索似乎具有相似的通过重放位置单元序列显示的机制在矩中表示这两个轨道在锋利的波浪（SWR）期间进行跑步和奔跑之后，在150-250 Hz中的瞬时活动爆发 LFP频段。2放置小鼠即将到来的轨迹的可能性匹配的细胞序列也经常发生 theta（5-12Hz）LFP振荡，3一种称为“ theta序列”的现象。评估大脑如何代表即将在Theta和SWR中进行的即将进行的跑步 SWR共同使我们更加了解大脑如何形成特定的发作。重要的是，奖励位置和环境变化已显示用于调节海马位置细胞和LFP。我们和其他4-5理论认为，这些地标和内容在啮齿动物任务中的变化以类似的方式行动人类情景记忆中的边界。拟议的研究介绍了一种新型的实验设计，以测试两个大鼠中的候选事件边界，奖励位置和任务规则过渡到单独颜色配对迷宫的一面。 AIM 1将重点介绍海马放置细胞和theta序列如何代表对奖励位置和环境边界过渡之间的空间，特别是这些如何引入新的和相互冲突的奖励地点时，表示形式发生了变化。 AIM 2将专注于清醒 SWR重播，还专注于如何代表奖励位置之间的段以及这些段表示形式与新引入的奖励位置集成在一起。该建议的完成项目将对情节记忆的神经机制提供重要的见解。这个项目将在实验和计算方法中提供严格的练习，并将在Kamran Diba的神经回路和记忆实验室是密歇根大学神经科学研究生课程的一部分。