GLUR5 KAINATE RECEPTOR ACTIVATION IN INTERNEURONS INCREASES TONIC INHIBITION OF PYRAMIDAL CELLS

We studied the modulation of GABAergic inhibition by glutamate and kai nate acting on GluR5-containing kainate receptors in the CA1 hippocamp al region. Glutamate, kainate or ATPA, a selective agonist of GluR5-co ntaining receptors, generates an inward current in inhibitory interneu rons and cause repetitive action potential firing. This results in a m assive increase of tonic GABAergic inhibition in the somata and apical dendrites of pyramidal neurons. These effects are prevented by the Gl uR5 antagonist LY 293558. Electrical stimulation of excitatory afferen ts generates kainate receptor-mediated excitatory postsynaptic current s (EPSCs) and action potentials in identified interneurons that projec t to the dendrites and somata of pyramidal neurons. Therefore glutamat e acting on kainate receptors containing the GluR5 subunit may provide a protective mechanism against hyperexcitability.