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By using the highly sensitive sniffer\u2010patch technique, we demonstrate that the activation of P2Y receptors, bradykinin receptors and protease activated receptors all stimulate glutamate release from cultured or acutely dissociated astrocytes. Of these receptors, we have utilized PAR1 as a model system because of favourable pharmacological and molecular tools, its prominent expression in astrocytes and its high relevance to neuropathological processes. Astrocytic PAR1\u2010mediated glutamate release<jats:italic>in vitro<\/jats:italic>is Ca<jats:sup>2+<\/jats:sup>dependent and activates NMDA receptors on adjacent neurones in culture. Activation of astrocytic PAR1 in hippocampal slices induces an APV\u2010sensitive inward current in CA1 neurones and causes APV\u2010sensitive neuronal depolarization in CA1 neurones, consistent with release of glutamate from astrocytes. PAR1 activation enhances the NMDA receptor\u2010mediated component of synaptic miniature EPSCs, evoked EPSCs and evoked EPSPs in a Mg<jats:sup>2+<\/jats:sup>\u2010dependent manner, which may reflect spine head depolarization and consequent reduction of NMDA receptor Mg<jats:sup>2+<\/jats:sup>block during subsequent synaptic currents. The release of glutamate from astrocytes following PAR1 activation may also lead to glutamate occupancy of some perisynaptic NMDA receptors, which pass current following relief of tonic Mg<jats:sup>2+<\/jats:sup>block during synaptic depolarization. These results suggest that astrocytic G\u2010protein coupled receptors that increase intracellular Ca<jats:sup>2+<\/jats:sup>can tune synaptic NMDA receptor responses.<\/jats:p>","DOI":"10.1113\/jphysiol.2007.130377","type":"journal-article","created":{"date-parts":[[2007,4,6]],"date-time":"2007-04-06T00:39:09Z","timestamp":1175819949000},"page":"1057-1081","source":"Crossref","is-referenced-by-count":192,"title":["Astrocytic control of synaptic NMDA receptors"],"prefix":"10.1113","volume":"581","author":[{"given":"C. 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