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的基础机制。 具体而言，目标是研究脑干快速眼动（REM）睡眠结构在大鼠睡眠依赖性学习中发挥哪些作用。阐明睡眠依赖性学习和记忆的机制将使认知研究领域更加接近开发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，核亚焦点背侧部分中的P-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。 从这个假设中，已经产生了四个可检验的问题：1。在学习任务培训后，P-波发电机的补充激活是否增强了信息处理效率，从而提高了学习？ 在进行双向主动避免测试试验会议后，立即通过离散的卡尔巴乔尔显微注射直接激活P波生成器。 在不受干扰的睡眠时间六个小时后，将在重新试验中检查这种补充激活的效果。 2。在REM睡眠期间，P-波发电机的激活会增强记忆的生理过程，该过程自然会在学习后睡眠期间发生？ 测试此问题的程序与问题1的程序相同，只是在测试和重新测试试验之间的六小时内被剥夺了这些大鼠的睡眠。 3。消除P波发生器中的细胞是否会削弱睡眠后重新测试试验中的学习能力？ p波产生细胞将直接通过海藻酸显微注射来直接消除。 这些P波产生细胞病变的大鼠的重试性能将与假病变大鼠的重新进行比较。 4。由于P波产生细胞的激活，在学习后REM睡眠期间P波的密度增加吗？ 在学习试验会议后，P波和P波产生细胞的单细胞单位活性将同时记录在自由移动的大鼠中。 该提案在机械层面上解决了一个总体问题，睡眠的功能是什么？并有望在朝向治疗的方向上进一步依赖睡眠的认知研究，以解决与喷气滞后，转移工作，睡眠剥夺和脑干退化性疾病相关的认知障碍。