Mechanisms Underlying the Cognitive Function of Sleep

睡眠认知功能的机制

• 批准号: 6747678
• 负责人: Subimal Datta
• 金额: $ 32.6万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6747678
• 关键词: REM sleep; behavioral /social science research tag; cognition; cognition disorders; dorsal raphe nucleus; laboratory rat; learning; locus coeruleus; memory; microelectrodes; microinjections; neural information processing; performance; single cell analysis; sleep deprivation; sleep disorders

The long-term objective of this application is to identify the cellular mechanisms underlying the cognitive function of sleep. Specifically, the goal is to investigate what role brainstem rapid eye movement (REM) sleep generating structures play in sleep-dependent learning in the rat. Clarifying the mechanisms of sleep-dependent learning and memory will move the field of cognitive research closer to the development of effective treatments for cognitive deficiencies associated with sleep disorders. The central hypothesis of this proposal is that activation of phasic P-wave generating cells in the dorsal part of the nucleus subcoeruleus is critical for sleep-dependent learning and memory processing. From this hypothesis, four testable questions have been generated: 1. After learning task training, does supplementary activation of the P-wave generator enhance information processing efficiency, resulting in improved learning? Immediately after a session of two-way active avoidance test trials, the P-wave generator will be directly activated by a discrete microinjection of carbachol. The effect of this supplementary activation will be examined in retest trials after a six hour period of undisturbed sleep. 2. Does the activation of the P-wave generator during REM sleep enhance a physiological process of memorization which naturally occurs during post-learning sleep? The procedure for testing this question is the same as that of question 1, except that these rats are REM sleep deprived for the six hour period between test and retest trials. 3. Does the elimination of cells in the P- wave generator attenuate learning abilities in post-sleep retest trials? P-wave generating cells will be directly eliminated by a discrete microinjection of kainic acid. The retest performance of these P-wave generating cell lesioned rats will be compared with that of the sham lesioned rats. 4. Is the increased density of P-waves during post-learning REM sleep due to the activation of P-wave generating cells? P-waves and single cell unitary activity of P-wave generating cells will be simultaneously recorded in freely moving rats after a session of learning trials. This proposal addresses at the mechanistic level, the general question, what is the function of sleep? and also promises to further sleep-dependent cognitive research in the direction toward treatments for cognitive impairments associated with jet lag, shift work, sleep deprivation and brainstem degenerative disorders.

该应用的长期目标是确定睡眠认知功能背后的细胞机制。 具体来说，我们的目标是研究脑干快速眼动 (REM) 睡眠生成结构在大鼠睡眠依赖性学习中发挥的作用。阐明睡眠依赖性学习和记忆的机制将使认知研究领域更接近开发针对与睡眠障碍相关的认知缺陷的有效治疗方法。该提议的中心假设是，蓝下核背侧部分的相位 P 波生成细胞的激活对于睡眠依赖性学习和记忆处理至关重要。 根据这个假设，产生了四个可测试的问题： 1.学习任务训练后，P波发生器的补充激活是否会提高信息处理效率，从而改善学习？ 在双向主动回避测试试验结束后，P波发生器将立即通过离散的卡巴胆碱微量注射来激活。 这种补充激活的效果将在六小时不受干扰的睡眠后的重新测试中进行检查。 2. 快速眼动睡眠期间 P 波发生器的激活是否会增强学习后睡眠期间自然发生的记忆生理过程？ 测试该问题的程序与问题 1 相同，不同之处在于这些大鼠在测试和重新测试试验之间的 6 小时内被剥夺快速眼动睡眠。 3. P 波发生器中细胞的消除是否会削弱睡眠后重新测试试验中的学习能力？ P波产生细胞将通过红藻氨酸的离散显微注射直接消除。 这些P波产生细胞损伤大鼠的再测试表现将与假损伤大鼠的重新测试表现进行比较。 4. 学习后快速眼动睡眠期间 P 波密度增加是否是由于 P 波生成细胞的激活所致？ 经过一段学习试验后，将在自由活动的大鼠中同时记录 P 波和 P 波产生细胞的单细胞单一活动。 该提案从机械层面解决了一般性问题：睡眠的功能是什么？并承诺进一步开展与睡眠相关的认知研究，以治疗与时差、轮班工作、睡眠剥夺和脑干退行性疾病相关的认知障碍。