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: 10202530
• 负责人: Nathaniel Reid Kinsky
• 金额: $ 6.64万
• 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/10202530
• 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.

大脑如何能够在不破坏现有记忆的情况下同时支持新信息的学习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性海马体中获得的新学习整合到更稳定的皮质网络中。彻底检验这一理论需要能够在多天内跟踪皮质神经元的长期、与学习相关的变化，但由于技术限制，直到最近这还是很困难的。虽然钙成像技术的进步现在允许长期跟踪体内神经元活动，但其有限的时间分辨率阻碍了对海马-皮质相互作用的一种可能候选者的研究：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。我建议直接检验这样的假设：睡眠期间海马-皮质相互作用促进学习相关可塑性的诱导和维持。为了解决这一假设，我建议将海马体的电生理记录与啮齿类动物前额皮质的长期钙成像相结合，前额皮质是长期记忆回忆所必需的区域。在目标 1 中，我将描述睡眠期间海马 SWR 活动如何影响获得联想学习任务后前额叶神经元活动的长期、与学习相关的变化。在目标 2 中，我将利用睡眠剥夺来测试睡眠、长期记忆和前额神经元可塑性之间的关系。在目标 3 中，我将描述海马-前额叶对话的时间过程，支持逐渐习得更困难的长期记忆任务。睡眠障碍是当今社会的一种普遍现象，在正常衰老过程中出现，并在阿尔茨海默病 (AD) 的病程中缓慢加剧。此外，睡眠不足会加剧海马体和皮质中 tau 蛋白和淀粉样蛋白（AD 的两种标志性病变）的患病率。了解睡眠如何影响海马皮质协调和长期可塑性，可以为睡眠不足、正常衰老和 AD 引起的记忆缺陷提供有价值的见解，从而指导改善记忆结果的干预措施。