LONG-LASTING CHANGES OF CALCIUM OSCILLATIONS IN ASTROCYTES - A NEW FORM OF GLUTAMATE-MEDIATED PLASTICITY

Long-term changes of synaptic strength in the central nervous system a re mediated by an increase of cytosolic calcium concentration ([Ca2+]( i)) following activation of excitatory neurotransmitter receptors. The se phenomena, which represent a possible cellular basis for learning a nd memory processes in eukaryotes, are believed to be restricted to ne urons. Here we provide evidence for a long-term change of the response elicited by the excitatory neurotransmitter glutamate in a non-neuron al cell population of the central nervous system, i.e. visual cortical astrocytes in culture. Stimulation with glutamate induces in astrocyt es a regular pattern of [Ca2+](i) oscillations. A second stimulation, after an interval ranging from 2 to 60 min, induces an oscillatory res ponse characterized by an increased frequency. Induction of this chang e in the astrocyte response is abolished by a specific inhibitor of th e nitric oxide synthase and recovers upon exogenous nitric oxide gener ation or addition of a permeant cGMP analogue. Local brief pulses of g lutamate to individual astrocytes, at a rate of 1 Hz, also elicit [Ca2 +](i) oscillations whose frequency increases following a second series of pulses. The long-lasting modification in the [Ca2+](i) oscillatory response induced by glutamate in astrocytes demonstrates that in the central nervous system cellular memory is not a unique feature of neur ons.