DESCRIPTION The overall goal of this proposal is to test the hypothesis that astrocytes modulate synaptic transmission. Previous work from the applicant's laboratory has shown that calcium elevations in astrocytes lead to delayed calcium elevation in adjacent neurons. In this proposal, the applicant will address three tightly interrelated hypothesis designed to examine the role of astrocytes. First, he will test the hypothesis that Ca++ dependent glutamate release from astrocytes requires the SNARE fusion complex. Second, he will test the hypothesis that activation of astrocytes causes mGluR and NMDA receptor dependent synaptic modulation. Finally, he will test the hypothesis that astrocytes regulate synaptic transmission by controlling intracellular calcium levels in presynaptic terminals. If successful, these experiments will provide solid information on the role of astrocytes in synaptic transmission.