GLUTAMATE-MEDIATED ASTROCYTE NEURON SIGNALING

NEUROTRANSMITTER released from neurons is known to signal to neighbour ing neurons and glia(1-3). Here we demonstrate an additional signallin g pathway in which glutamate is released from astrocytes and causes an NMDA (N-methyl-D-aspartate) receptor-mediated increase in neuronal ca lcium. Internal calcium was elevated and glutamate release stimulated by application of the neuroligand bradykinin to cultured astrocytes. E levation of astrocyte internal calcium was also sufficient to induce g lutamate release. To determine whether this released glutamate signals to neurons, we studied astrocyte-neuron co-cultures. Bradykinin signi ficantly increased calcium levels in neurons co-cultured with astrocyt es, but not in solitary neurons. The glutamate receptor antagonists D- 2-amino-5-phosphonopentanoic acid and D-glutamylglycine prevented brad ykinin-induced neuronal calcium elevation. When single astrocytes were directly stimulated to increase internal calcium and release glutamat e, calcium levels of adjacent neurons were increased; this increase co uld be blocked by D-glutamyl-glycine. Thus, astrocytes regulate neuron al calcium levels through the calcium-dependent release of glutamate. -