A. Rodriguezmoreno et al., KAINATE RECEPTORS PRESYNAPTICALLY DOWN-REGULATE GABAERGIC INHIBITION IN THE RAT HIPPOCAMPUS, Neuron, 19(4), 1997, pp. 893-901
Using microcultured neurons and hippocampal slices, we found that unde
r conditions that completely block AMPA receptors, kainate induces a r
eduction in the effectiveness of GABAergic synaptic inhibition. Evoked
inhibitory postsynaptic currents (IPSCs) were decreased by kainate by
up to 90%, showing a bell-shaped dose-response curve similar to that
of native kainate-selective receptors. The down-regulation of GABAergi
c inhibition was not affected by antagonism of metabotropic receptors,
while it was attenuated by CNQX. Kainate increased synaptic failures
and reduced the frequency of miniature IPSCs, indicating a presynaptic
locus of action. In vivo experiments using brain dialysis demonstrate
d that kainate reversibly abolished recurrent inhibition and induced a
n epileptic-like electroencephalogram (EEG) activity. These results in
dicate that kainate receptor activation downregulates GABAergic inhibi
tion by modulating the reliability of GABA synapses.