Gap Junctions and Connexins in Developing CNS

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DESCRIPTION (provided by the applicant): Gap junctions are membrane specializations that link cells directly for electrical, ionic and metabolic communication. In the central nervous system of adult rats, gap junctions are abundant between glial (supporting) cells, but relatively few are present between neurons. During development, gap junctional coupling is strong between neurons and have been reported to occur between neurons and glial cells. An integrated approach using a combination of electron microscopic freeze-fracture immunocytochemistry, confocal microscopic immunocytochemistry, and single-cell RT-PCR will be used to identify the gap junction "connexin" protein molecules that are present in neurons and glia, determine if neurons share gap junctions with glia, and assay the distribution of neuronal gap junctions in early postnatal CNS. Gap junctions are thought to provide pathways for metabolic and regulatory molecules during the period of neuronal differentiation and maturation. Areas of the CNS to be examined are locus coeruleus, somatosensory cortex, and spinal cord. Obtaining accurate data regarding the composition and intercellular coupling relationships in those areas will be essential for understanding mechanisms regulating: (1) normal development of neurons and glia in the CNS; (2) postnatal organization and reorganization of neuronal circuits; (3) programmed cell death during normal sculpting of the neuron pools in early postnatal development; (4) neuronal synchronization and rhythmic bursting activity in developing and adult neurons; and (5) abnormal synchronous bursting activity, such as in epileptic seizures.