Block of glutamate-glutamine cycle between astrocytes and neurons inhibits epileptiform activity in hippocampus.

Recurrent epileptiform activity occurs spontaneously in cultured CNS
neurons and in brain slices in which GABA inhibition has been
blocked. We demonstrate here that pharmacological treatments
resulting in either the block of glutamine production by astrocytes or
the inhibition of glutamine uptake by neurons suppress or markedly
decrease the frequency of spontaneous epileptiform discharges both
in primary hippocampal cultures and in disinhibited hippocampal
slices. These data point to an important role for the neuron-astrocyte
metabolic interaction in sustaining episodes of intense rhythmic
activity in the CNS, and thereby reveal a new potential target for
antiepileptic treatments.