The purpose of the proposed studies is to define the functions of neuroglia and thereby to expand present understanding of the interdependence between neurons and glia. The emphasis is on the role of glial cells in regulating the neuronal microenvironment with respect to ions and presumptive neurotransmitter compounds. The effects of variations in the concentration of these substances on the properties of the glial cells will be studied, as well as, the movement of such substances among glial cells. In view of the proposed role of glial cells not only in nervous system maintenance but also in degeneration and repair processes the morphological and physiological properties of these cells will be studied during degeneration and regeneration of neuronal axons. Possible mechanisms for coordination of neuronal and glial activity will also be investigated in these preparations. The experiments will involve 1) transmembrane electrophysiological measurements from glia with both conventional intracellular electrodes and patch clamp electrodes, 2) optical measurement of the osmotic properties of neuroglia, 3) fluorometric analysis of glial cell constituents and the movement of tracers among glial cells in the presence or absence of neurons, 4) morphological studies in the light and electron microscope of the structure and turnover of glial cells during degeneration and regeneration. These studies should provide a better understanding of neuron-glial interactions and also some insight into processes which underlie brain edema, including that accompanying multiple sclerosis and the pathophysiology of epilepsy.
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