The aim of this program is to understand the principles, and mechanisms that govern inter cellular communication between astrocytes and between astrocytes and neurons. Although neurons are the central players in cellular communication and information processing in the brain, recent discoveries of glial cell types, excitability and signalling properties have shown that glial cells may play an important role in long distance signalling in the brain. During embryonic development the importance of specific humoral signals from glial cells are important for neuronal survival and development. In the adult, synaptic activity is being monitored by astrocytes closest to the synaptic fields. Methods have become available for obtaining relatively pure cultures of different types of astrocytes, as well as mixed neuronal and glial cultures. Methods are also available for light microscopic analysis of cells in splice preparations. Fluorescence microscopy with digital image processing will be used as the technique to monitor intracellular signalling in astrocytes and neurons in order to describe specific communication between cells. The intracellular calcium changes in response to activation of various neurotransmitter receptor systems on astrocytes isolated from different regions of brain will be investigated. These results will be correlated with companion studies on astrocytes in situ, by measurement of cellular responses in the brain slice preparation.