Segmentation and integration of experience in hippocampal neuronal representations

海马神经元表征经验的分割和整合

• 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
• 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

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.

情景记忆是一系列一起回忆起来的时刻;这些时刻通常具有独特的组合 时间地点和内容尽管我们的记忆经验是， 分类，我们还不太清楚大脑是如何将瞬间归类为情节的。据推测， 海马体对特定环境刺激中的事件边界，位置或时间的变化， 触发进入下一个所表示的情节的移动。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不同的事件，表现为记忆力下降 尽管情景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尚未得到很好的理解， fMRI的分辨率限制。啮齿类动物提供了一个了解这些事件的潜在神经机制的窗口 通过单个神经元和局部场电位的大规模体内电生理记录的边界 (LFP)在海马区。已知海马体在情景记忆巩固中起作用， 检索，以及规划和学习。计划和情景记忆提取似乎有类似的 通过重放位置单元序列显示的机制， 在150-250 Hz的尖波波纹（SWR）、瞬时活动爆发期间， LFP带。2位置细胞序列匹配大鼠即将到来的轨迹的可能性也经常发生在 θ（5- 12 Hz）LFP振荡，3一种称为“θ序列”的现象。评估大脑是如何 表示theta和SWR期间即将进行的运行，同时确定在theta和SWR期间如何重播过去的运行。 SWR的结合使我们更接近了解大脑如何形成特定事件。重要的是，奖励 位置和环境的变化已经显示出调节海马定位细胞和LFP。我们 和其他人4 -5的理论，这些里程碑和内容的变化，在啮齿动物的任务，以类似的方式行动的事件 人类情景记忆的界限这项研究引入了一种新的实验设计， 大鼠中的候选事件边界、奖励位置和任务规则转换配对为单独着色 迷宫的两边目标1将集中在辨别海马位置细胞和θ序列如何代表 奖励位置对之间的空间和环境边界过渡，以及这些 表示在引入新的和冲突的奖励位置时改变。目标2将专注于清醒 SWR重放，也关注奖励位置之间的段如何表示，以及这些 表示与新引入的奖励位置集成在一起。完成这一拟议 项目将提供重要的洞察神经机制的情景记忆。该项目将 提供严格的实践，在实验和计算方法，将发生在卡姆兰迪巴的 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。