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。具体来说，目的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所起的作用。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。该假说的核心假设是，蓝下核背侧相p波产生细胞的激活对睡眠依赖性学习和记忆处理至关重要。从这个假设中，产生了四个可测试的问题：1。学习任务训练后，补充激活p波发生器是否能提高信息处理效率，从而提高学习效果？在一组双向主动回避测试试验后，p波发生器将通过离散的微量注射甲醇直接激活。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. 在快速眼动睡眠期间p波发生器的激活是否会增强学习后睡眠中自然发生的生理记忆过程？测试这个问题的过程与问题1相同，除了在测试和重新测试之间的六个小时内，这些老鼠被剥夺了快速眼动睡眠。3. 在睡眠后的重测试验中，P波产生细胞的消除是否会减弱学习能力？产生p波的细胞将通过离散微量注射kainic酸直接消除。将这些p波产生细胞损伤大鼠的重测性能与假损伤大鼠进行比较。4. 学习后快速眼动睡眠中p波密度的增加是由于p波产生细胞的激活吗？在一组学习试验后，将同时记录自由运动大鼠的p波和产生p波细胞的单细胞活动。这个建议在机制层面上解决了一个普遍的问题，睡眠的功能是什么？同时，该研究还有望进一步推动睡眠依赖认知研究，朝着治疗与时差、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.