SITE AND RECEPTOR MECHANISM OF MK801 DELTA STIMULATION

描述（改编自申请人摘要）：目前的证据表明 睡眠的自我平衡（恢复）过程与 NREM睡眠中高振幅、慢（δ）EEG的量。 的 研究者已经发现，阻断由 清醒时GluRs的NMDA亚群强烈刺激NREM δ 在随后的睡眠中。 研究人员现在已经证明了这种效果 与光谱以及周期分析，并表明，MK-801-诱导 NREM和REM频谱的变化与睡眠剥夺的变化密切平行， 最有效的生理睡眠刺激。 除了其 对于睡眠研究的重要意义，这个NDP提供了一个新的，高度可靠的 GluR扰动对皮质神经元影响的体内研究模型 电生理学 谷氨酸是主要的兴奋性神经递质， 在正常脑功能和病理条件下的中心作用 包括兴奋性中毒可能还有精神分裂症 研究人员的研究将确定神经结构， 产生NDP响应于微量注射MK-801和竞争性NMDA 拮抗剂CPPene。 注射部位包括高度可塑的边缘系统 对通道阻滞有急性反应的高代谢结构， 具有高密度的NMDA受体，这些结构与NREM睡眠有关 调节，以及产生EEG的电路中涉及的结构 振荡 这些研究将是第一个系统的调查， 双侧NMDA后定量睡眠（和清醒）EEG的变化 受体阻滞剂在特定的大脑结构。 他们不是随机的 搜索任何睡眠脑电图的影响，但旨在复制与 显微注射高度可靠的NDP，研究者发现全身 给予MK-801。 研究人员的研究可以提供新的 对系统性GluR生理学，睡眠稳态机制， 精神分裂症和抑郁症的NREM睡眠异常与NMDA（PCP） 精神分裂症的模型 这也可能导致一部小说的发展 这类催眠药刺激更多的生理睡眠脑电图。

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.