We studied the modulation of GABAergic inhibition by glutamate and kainate
acting on GluR5-containing kainate receptors in the CA1 hippocampal region.
Glutamate, kainate or ATPA, a selective agonist of GluR5-containing receptors,
generates an inward current in inhibitory interneurons and cause repetitive
action potential firing. This results in a massive increase of tonic GABAergic
inhibition in the somata and apical dendrites of pyramidal neurons. These
effects are prevented by the GluR5 antagonist LY 293558. Electrical stimulation
of excitatory afferents generates kainate receptor-mediated excitatory postsynaptic
currents (EPSCs) and action potentials in identified interneurons that project
to the dendrites and somata of pyramidal neurons. Therefore glutamate acting
on kainate receptors containing the GluR5 subunit may provide a protective
mechanism against hyperexcitability.
