IDENTIFICATION OF GLUTAMATE-RECEPTOR SUBTYPES MEDIATING INPUTS TO BIPOLAR CELLS AND GANGLION-CELLS IN THE TIGER SALAMANDER RETINA

1. The effects of glutamate receptor agonists and antagonists on bipolar cells and ganglion cells were studied with the use of intracellular and extracellular recording in the superfused, isolated, flat-mounted tiger salamander retina. The goal of the experiments was to correlate glutamate receptor subtypes with their localization at specific synaptic sites in the tiger salamander retina. The drugs tested were the kainate/a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the N-methyl-D-aspartate (NMDA) receptor antagonist 3-(C+/-)-2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP) and L-2-amino-4-phosphonobutyrate (L-AP4). 2. The light responses of hyperpolarizing bipolar cells were suppressed by 20 muM CNQX, whereas L-AP4 had no effect on their light responses. In contrast, 20 muM CNQX had no effect on depolarizing bipolar cells, whereas L-AP4 abolished the light responses of these cells. 3. The light offset responses of OFF and ON-OFF ganglion cells were completely blocked by concentrations of CNQX as low as 5 muM. The light onset responses of ON-OFF ganglion cells were blocked when the concentration of CNQX was raised to 20 muM. In addition, 30 muM CPP partially blocked the light onset responses of ON-OFF ganglion cells but had a lesser effect on the light offset responses. 4. Twenty micromolars of CNQX blocked a transient component, and 20 muM CPP blocked a sustained component of the light response of sustained-ON ganglion cells. 5. These results indicate that there are distinct differences in the pharmacology of glutamatergic synapses between the ON pathway and OFF pathway. In addition, the relative contribution of kainate/AMPA receptors compared with NMDA receptors may play a role in shaping transient versus sustained responses in retinal ganglion cells.