The Influence of Sleep on Plasticity and Stability in Hippocampal-Prefrontal Networks.

睡眠对海马-前额叶网络可塑性和稳定性的影响。

• 批准号: 10042003
• 负责人: Nathaniel Reid Kinsky
• 金额: $ 6.49万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10042003
• 关键词: Address; Alzheimer' s Disease; Alzheimer' s disease pathology; Amyloid beta-Protein; Animal Behavior; Animals; Appearance; Atrophic; Brain; Calcium; Communication; Computing Methodologies; Disease; Electrophysiology (science); Episodic memory; Extinction (Psychology); Frequencies; Future; Hippocampus (Brain); Image; Impairment; Interruption; Intervention; Knowledge; Learning; Long-Term Potentiation; Maintenance; Mediating; Memory; Memory Loss; Memory impairment; Mental disorders; Monitor; Neocortex; Neurodegenerative Disorders; Neurons; Outcome; Pathologic; Performance; Prefrontal Cortex; Prevalence; Rest; Rodent; Short-Term Memory; Sleep; Sleep Deprivation; Sleep disturbances; Slow-Wave Sleep; Societies; System; Testing; Time; awake; classical conditioning; fear memory; healthy aging; improved; in vivo; insight; long term memory; memory consolidation; memory recall; neural correlate; normal aging; prevent; relating to nervous system; sleep abnormalities; tau Proteins; temporal measurement; theories

How the brain is able to simultaneously support learning of new information without corrupting existing memories remains an unanswered question. Systems consolidation theory argues that successful memory consolidation requires integrating new learning - acquired in the highly plastic hippocampus - into more stable cortical networks. Thoroughly testing this theory requires the ability to track long-term, learning-related changes in cortical neurons across multiple days, which has been difficult until recently due to technological limitations. While advances in calcium imaging now permit the long-term tracking of neuron activity in vivo, its limited temporal resolution prevents the study of one likely candidate for hippocampal-cortical interactions: high-frequency hippocampal oscillations dubbed sharp-wave ripples (SWRs) that occur during slow-wave sleep (SWS). I propose directly testing the hypothesis that hippocampal-cortical interactions during sleep facilitate the induction and maintenance of learning related plasticity. To address this hypothesis, I propose combining electrophysiological recordings in the hippocampus with long-term calcium imaging in the prefrontal cortex of rodents, a region necessary for long-term memory recall. In Aim 1, I will characterize how hippocampal SWR activity during sleep influences long-term, learning-related changes in prefrontal neuron activity following the acquisition of an associative learning task. In Aim 2, I will utilize sleep deprivation to test the relationship between sleep, long-term memory, and prefrontal neuron plasticity. In Aim 3, I will characterize the time course of the hippocampal-prefrontal dialog supporting the gradual acquisition of a more difficult long-term memory task. Sleep disturbances are endemic to today’s society, emerge during normal aging, and slowly increase through the course of Alzheimer’s Disease (AD). Moreover, sleep deprivation can exacerbate the prevalence of tau and amyloid beta, two hallmark AD pathologies, in the hippocampus and cortex. Understanding how sleep influences hippocampal-cortical coordination and long-term plasticity could provide valuable insights into memory deficits caused by sleep deprivation, normal aging, and AD, which could guide interventions to improve memory outcomes.

大脑如何能够同时支持学习新信息而不破坏现有的记忆仍然是一个悬而未决的问题。系统巩固理论认为，成功的记忆巩固需要将在高度可塑的海马体中获得的新学习整合到更稳定的皮层网络中。彻底测试这一理论需要能够在多天内跟踪皮层神经元中与学习相关的长期变化，由于技术限制，直到最近才很难做到这一点。虽然钙成像的进步现在允许在体内长期跟踪神经元活动，但其有限的时间分辨率阻止了对海马-皮层相互作用的一个可能候选者的研究：在慢波睡眠（SWS）期间发生的被称为尖波波纹（SWR）的高频海马振荡。我建议直接测试的假设，即大脑皮层在睡眠中的相互作用，促进诱导和维持学习相关的可塑性。为了解决这一假设，我建议结合海马体的电生理记录与长期钙成像在前额叶皮层的啮齿类动物，一个区域需要长期记忆回忆。在目标1中，我将描述海马SWR活动在睡眠中如何影响长期的，学习相关的前额叶神经元活动的变化后，收购的联想学习任务。在目标2中，我将利用睡眠剥夺来测试睡眠、长期记忆和前额叶神经元可塑性之间的关系。在目标3中，我将描述支持逐渐获得更困难的长期记忆任务的前额叶-前额叶对话的时间过程。睡眠障碍是当今社会的地方病，在正常衰老期间出现，并在阿尔茨海默病（AD）的过程中缓慢增加。此外，睡眠剥夺可加剧海马体和皮质中tau蛋白和淀粉样蛋白β的流行，这是两种标志性AD病理。了解睡眠如何影响大脑皮层协调和长期可塑性可以为睡眠剥夺，正常衰老和AD引起的记忆缺陷提供有价值的见解，这可以指导干预措施改善记忆结果。