COMPONENTS OF GLIAL RESPONSES TO EXOGENOUS AND SYNAPTIC GLUTAMATE IN RAT HIPPOCAMPAL MICROCULTURES

Although glia are known to be sensitive to exogenously applied neurotr ansmitter substances, little is known about how glia respond to neuron al activity on the millisecond time scale of individual synaptic event s. We have explored the electrophysiological effects of excitatory neu ronal signaling on glial cells in rat hippocampal microcultures. Exoge nous applications of glutamate analogs to islands of glia revealed a l arge ionotropic AMPA receptor-mediated current and a smaller current m ediated by electrogenic glutamate uptake. Glia demonstrated no evidenc e of NMDA or metabotropic receptor-mediated currents or membrane condu ctance changes. Despite the dominant contribution of AMPA receptors to exogenous glutamate applications in glia, AMPA receptor currents cont ributed only similar to 20% to the response of glia to endogenous glut amate release from solitary excitatory neurons. Electrogenic glutamate uptake contributed strongly to glial responses to neuronal stimulatio n. In addition, some glia exhibited a residual current in response to neuronal stimulation that was not attributable to calcium-dependent tr ansmitter release or to neuronal potassium efflux. These results help provide a context for understanding the role of glial transporters and receptors in nervous system signaling.