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

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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.