SITE AND RECEPTOR MECHANISM OF MK801 DELTA STIMULATION

描述(改编自申请人的摘要)：当前证据表明 睡眠的动态平衡(疗养)过程与 NREM睡眠中高幅度、慢(增量)脑电波的数量。这个 研究人员发现，对阳离子通道的阻断由 清醒时GluR的NMDA亚群强烈刺激NREM增量 在随后的睡眠中。研究人员现在已经证明了这一效应 光谱分析和周期分析表明，MK-801诱导 NREM和REM频谱的变化与睡眠剥夺密切相关， 最有效的生理睡眠刺激。除了它的 对于睡眠研究的意义，该NDP提供了一种新颖的、高度可靠的 葡萄糖摄取对大脑皮层影响的活体研究模型 电生理学。谷氨酸，主要的兴奋性神经递质，扮演着 在正常脑功能和病理状态中的中心作用 包括兴奋性毒性，可能还有精神分裂症。 研究人员的研究将确定神经结构可以 微量注射MK-801和竞争性NMDA产生NDP 拮抗剂CPPene。注射部位包括高度可塑性的边缘 对高代谢和通道阻断有敏锐反应的结构 有高密度的NMDA受体，与NREM睡眠有关的结构 调节，以及产生脑电的电路中涉及的结构 震荡。这些研究将是第一次系统地调查 双侧NMDA后量化睡眠(和清醒)脑电的变化 受体在特定的大脑结构中被阻断。它们不是随机的 搜索任何睡眠脑电效果，但目标是复制 研究人员发现，显微注射是一种高度可靠的NDP， MK-801的管理。调查人员的研究可能会提供新的 对全身性Glur生理学、睡眠动态平衡机制的见解， 精神分裂症和抑郁症患者的NREM睡眠异常与NMDA(PCP) 精神分裂症的典范。这也可能导致一部小说的发展 一类催眠药，能刺激更具生理性的睡眠脑电。

DESCRIPTION (Adapted from applicant's abstract): Current evidence indicates that the homeostatic (recuperative) processes of sleep are proportional to the amount of high amplitude, slow (delta) EEG within NREM sleep. The investigator has discovered that blockade of the cation channel gated by the NMDA subpopulation of GluRs during waking intensely stimulates NREM delta during subsequent sleep. The investigator has now demonstrated this effect with spectral as well as period analysis and shown that MK-801-induced changes in NREM and REM spectra closely parallel those of sleep deprivation, the most potent physiological sleep stimulus. In addition to its significance for sleep research, this NDP provides a novel, highly reliable model for in vivo studies of the effects of GluR perturbations on cortical electrophysiology. Glutamate, the main excitatory neurotransmitter, plays a central role in normal brain function and in pathological conditions including excitotoxicity and, possibly, schizophrenia. The investigator's research will identify the neural structures that can produce NDP in response to microinjection of MK-801 and the competitive NMDA antagonist CPPene. Sites for injection include highly plastic limbic structures that respond acutely to channel blockade with hypermetabolism and have high densities of NMDA receptors, structures implicated in NREM sleep regulation, and structures involved in the circuits that generate EEG oscillations. These studies will be the first systematic investigation of changes in quantified sleep (and waking) EEG following bilateral NMDA receptor blockade in specific brain structures. They are not a random search for any sleep EEG effects but are aimed at duplicating with microinjection the highly reliable NDP the investigator found with systemic administration of MK-801. The investigator's research could provide new insights into systemic GluR physiology, mechanisms of sleep homeostasis, NREM sleep abnormalities in schizophrenia and depression, and the NMDA (PCP) model of schizophrenia. It might also lead to the development of a novel class of hypnotics that stimulates a more physiological sleep EEG.