Astrocytes are required for the oscillatory activity in cultured hippocampal neurons

Synchronous oscillations of intracellular calcium concentration ([Ca2+](i)) and of membrane potential occurred in a limited population of glutamatergi c hippocampal neurons grown in primary cultures. The oscillatory activity o ccurred in synaptically connected cells only when they were in the presence of astrocytes. Microcultures containing only one or a few neurons also dis played oscillatory activity, provided that glial cells participated in the network. The glutamate-transporter inhibitors L-trans-pyrrolidine-2,4-dicar boxylic acid (PDC) and dihydrokainate, which produce an accumulation of glu tamate in the synaptic microenvironment, impaired the oscillatory activity. Moreover, in neurons not spontaneously oscillating, though in the presence of astrocytes, oscillations were induced by exogenous L-glutamate, but not by the stereoisomer D-glutamate, which is not taken up by glutamate transp orters. These data demonstrate that astrocytes are essential for neuronal o scillatory activity and provide evidence that removal of glutamate from the synaptic environment is one of the major mechanisms by which glial cells a llow the repetitive excitation of the postsynaptic cell.