GLUTAMATE-DEPENDENT ASTROCYTE MODULATION OF SYNAPTIC TRANSMISSION BETWEEN CULTURED HIPPOCAMPAL-NEURONS

The idea that astrocytes merely provide structural and trophic support for neurons has been challenged by the demonstration that astrocytes can regulate neuronal calcium levels. However, the physiological conse quences of astrocyte-neuron signalling are unknown. Using mixed cultur es of rat hippocampal astrocytes and neurons we have determined functi onal consequences of elevating astrocyte calcium levels on co-cultured neurons. Electrical or mechanical stimulation of astrocytes to increa se their calcium level caused a glutamate-dependent slow inward curren t (SIC) in associated neurons. Microinjection of ,2-bis(2-aminophenoxy )ethane-N,N,N',N'-tetraacetic acid (BAPTA) into astrocytes to prevent the stimulus-dependent increase in astrocyte calcium level, blocks the appearance of the neuronal SIG. Pharmacological manipulations indicat e that this astrocyte-dependent SIC is mediated by extracellular gluta mate acting on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate rece ptors. Additionally, stimulation of astrocytes reduced the magnitude o f action potential-evoked excitatory and inhibitory postsynaptic curre nts through the activation of metabotropic glutamate receptors. The de monstration that astrocytes modulate neuronal currents and synaptic tr ansmission raises the possibility that astrocytes play a neuromodulato ry role by controlling the extracellular level of glutamate.