Segmentation and integration of experience in hippocampal neuronal representations

情节记忆是一组一起回忆的时刻；这些时刻往往分享着一种独特的组合 时间、地点和内容。尽管我们对记忆的经验是落入这些分段的 在分类方面，人们还不太清楚大脑是如何将瞬间归类为情节的。从理论上讲， 海马体对环境特定刺激中的事件边界、位置或时间的变化 这会触发移动到下一个代表剧集。在人类中，房间边界和任务变化是 两个候选事件边界似乎分开了不同的事件，表现为记忆力下降 跨越这些边界的表现1尽管情节记忆对我们的日常生活很重要 经验，注意事件边界的神经机制并没有被很好地理解 功能磁共振成像的分辨率限制。啮齿动物为了解这些潜在的事件神经机制提供了一个窗口 通过大范围在体单个神经元电生理记录和局部场电位的边界 (LFP)在海马区。众所周知，海马体在情景记忆巩固和 检索，以及计划和学习。计划记忆和情景记忆提取似乎有相似之处 通过重放表示轨迹的位置单元格序列显示的机制 在尖锐波纹(SWR)期间运行之前和之后，在150-250赫兹的瞬时活动突发 LFP带2.与大鼠即将到来的轨迹的可能性相匹配的放置细胞序列也经常发生在 Theta(5-12赫兹)lfp振荡，3这种现象被称为“theta序列”。评估大脑如何 表示在theta和SWR期间即将进行的运行，同时确定如何在 SWR让我们更接近于了解大脑是如何形成特定事件的。重要的是，奖励 位置和环境的变化已经被证明调节海马区的地方细胞和LFP。我们 和其他4-5个理论认为，啮齿动物任务中的这些里程碑和内容变化的作用方式与事件类似 人类情节记忆中的界限。建议的研究引入了一种新的实验设计来测试两个 RAT中的候选事件边界、奖励位置和任务规则转换配对到单独着色 迷宫的两边。目标1将专注于辨别海马区细胞和theta序列如何代表 奖励位置对之间和环境边界转换处的空间，特别是这些 在引入新的和冲突的奖励地点时，表示法会发生变化。目标2将专注于唤醒 SWR回放，还关注奖励位置之间的分段如何表示以及如何表示 表示法与新引入的奖励地点整合在一起。完成这项建议 该项目将为情节记忆背后的神经机制提供重要的见解。这个项目将 在实验和计算方法方面提供严格的实践，并将在Kamran Diba 作为密歇根大学神经科学研究生项目的一部分，神经电路和记忆实验室。

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.