Connexins in Neuronal and Glial Gap Junctions in the Central Nervous System

缝隙连接是一种微观连接，四十年来人们一直知道它提供了 大脑、视网膜和脊髓中神经细胞之间的直接细胞间和代谢偶联。 以前，神经元之间的缝隙连接被认为很大，但很少见，而且只存在于少数几种类型之间 而且只在中枢神经系统的有限区域内存在。“小”缺口的发现 连接和它们在大脑中可能丰富的初步证据表明，“迷你” 缝隙结可能为微小的“亚阈值电小穗”的繁殖提供结构基础。 大脑中初级神经元的“部分尖峰”。我们建议使用新开发的高分辨率 免疫细胞化学方法[激光扫描共聚焦免疫荧光显微镜和冷冻破碎法 复制免疫金标记法(FIRL)电子显微镜]来检测、定量、确定蛋白质 小鼠脑内所有类别缝隙连接的组成和大小 对人脑中选定区域的“迷你”缝隙连接进行详细测量。我们将强调 分析那些主要负责思考和意识、学习和 记忆和精细运动控制(即大脑皮层、海马体、小脑和下橄榄)。这些 数据对于理解意识是如何产生的，一个人是如何从睡眠中醒来的是必不可少的 以及全身麻醉，记忆是如何产生的，在禁用过程中如何产生或失去精细的运动控制 帕金森症等疾病，以及治疗这些疾病的药物的开发 流程。

Gap junctions are microscopic connections that for four decades have been known to provide for direct intercellular and metabolic coupling between nerve cells in the brain, retina and spinal cord. Previously, gap junctions between neurons were thought to be large but rare, and only between a few types of non-cognitive neurons and only in limited areas of the central nervous system. The discovery of "mini" gap junctions and preliminary evidence for their possible abundance throughout the brain suggests that "mini" gap junctions may provide the structural basis for propagation of tiny "sub threshold electrical spikelets" or "partial spikes" in primary neurons throughout the brain. We propose to use newly developed high-resolution immunocytochemical methods [both laser scanning confocal immunofluorescence microscopy and freezefracture replica immunogold labeling (FRIL) electron microscopy] to detect, quantify, determine the protein composition of, and measure the sizes of all classes of gap junctions throughout the brain of mice and to make detailed measurements of "mini" gap junctions in selected regions of human brain. We will emphasize analysis of those regions that are primarily responsible for thinking and consciousness, learning and memory, and fine motor control (i.e., cerebral cortex, hippocampus, cerebellum, and inferior olive). These data are essential to the understanding of how consciousness is created, how a person awakes from sleep and general anesthesia, how memories are created, how fine motor control is created or lost during disabling diseases such as Parkinsonism, as well as for development of drugs to treat disorders of each of these processes.