Central nervous system astrocytes are strategically located in proximity to excitable neurons and are sensitive to changes in extracellular ion composition that follow neuronal activity. Brain glia participate in the homeostatic regulation of the neuronal microenvironment. Several mechanisms have been proposed to explain how astrocytes sense and react to changes in extracellular potassium concentration following both normal and abnormal neuronal activity. The main goal of this proposal is to investigate the electrophysiological and morphological bases of hippocampal astrocytes' involvement in the control of neuronal function with specific emphasis on the control of potassium homeostasis. The applicants will test the hypothesis that hippocampal astrocytes do not constitute a homogeneous population and that different ion channel mechanisms expressed and segregated in topographically distinct astrocytic subpopulations are responsible for """"""""spacial buffering"""""""" or """"""""siphoning"""""""" of excess potassium from the extracellular space. They also hypothesize that pathologies such as traumatic brain injury or epilepsy, both known to alter brain potassium homeostasis, alter normal mechanisms of potassium uptake and redistribution by glia.
The specific aims of the proposal are: 1) To characterize morphologically and electrophysiologically glial cells in rat hippocampal CA1 and CA3 subfields.; 2) To elucidate the role of glial voltage(c)dependent ion channels in the regulation of extracellular potassium; 3) To test the hypothesis that pathologies associated with neuronal cell death affect the expression of astrocytic mechanisms involved in the control of extracellular potassium. The results of these experiments will develop further understanding of the specific role of hippocampal astrocytes in the control of neuronal microenvironment. While mechanisms other than [K]1/2o1/2u1/2t and astrocytic ion channels are involved in glia(c)mediated control of neuronal activity (such as glutamate uptake, pH, etc.), the applicants will concentrate efforts on the above mentioned experimentally accessible yet poorly understood aspect of glia function. The outcome of the proposed experiments may be useful for further extrapolations applicable to other physiological aspects of glia(c)neuronal interactions.
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