Mechanisms Underlying the Cognitive Function of Sleep

这项应用的长期目标是确定睡眠认知功能背后的细胞机制。具体地说，目标是调查脑干快速眼动(REM)睡眠生成结构在大鼠睡眠依赖学习中扮演的角色。阐明睡眠依赖学习和记忆的机制将使认知研究领域更接近于开发与睡眠障碍相关的认知缺陷的有效治疗方法。这一建议的中心假设是，蓝斑下核背侧部分的相P波产生细胞的激活对睡眠依赖的学习和记忆处理至关重要。根据这一假设，本研究提出了四个可检验的问题：1.学习任务训练后，P波发生器的辅助激活是否提高了信息处理效率，从而改善了学习？在一段双向主动回避试验后，P波发生器将立即被离散的微量注射卡巴胆碱激活。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试验中进行检验。2.快速眼动睡眠中P波发生器的激活是否增强了自然发生在学习后睡眠中的记忆生理过程？这个问题的测试程序与问题1相同，只是这些大鼠在测试和重测试验之间的六个小时内被剥夺了REM睡眠。3.在睡眠后重测试验中，P波发生器中细胞的消失是否会削弱学习能力？P波产生细胞将通过离散微量注射红藻氨酸直接消除。将这些P波产生细胞损毁大鼠的复测成绩与假损毁大鼠进行比较。4.学习后REM睡眠中P波密度的增加是否是由于P波产生细胞的激活？在自由活动的大鼠进行一段学习试验后，将同时记录P波和P波产生细胞的单细胞单位活动。这项建议在机械层面上解决了一个普遍的问题，即睡眠的功能是什么？并承诺进一步开展睡眠依赖的认知研究，朝着治疗与时差、倒班工作、睡眠剥夺和脑干退行性疾病相关的认知障碍的方向发展。

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.