Abstract
Purpose:
In the OFF retinal pathway, parallel temporal channels are thought to arise from the selective expression of AMPA or kainate type glutamate receptors in the dendrites of different OFF bipolar cell types. AMPA receptors are thought to transmit high temporal frequency signals, whereas kainate receptors are presumed to encode lower temporal frequencies. We tested this hypothesis in the macaque retina, where the low (midget/parvocellular) and high frequency (parasol/magnocellular) temporal pathways have been well characterized.
Methods:
Retinas from adult rhesus macaques were obtained from the Tissue Distribution Program at the Oregon National Primate Research Center from animals used for unrelated experiments. Whole-cell voltage-clamp recordings were made from bipolar cells in light-adapted retinal slices. Light-evoked spikes and synaptic currents were recorded from ganglion cells in retinal wholemounts. The localization of the GluK1 kainate receptor subunit was examined using immunohistochemistry.
Results:
We recorded from five OFF bipolar cells types: flat midget bipolar (FMB; n = 33) and the diffuse bipolar (DB) cell types DB1 (n = 14), DB2 (n = 24), DB3a (n = 11) and DB3b (n = 20). We found that glutamate-evoked responses in all types were strongly suppressed (>90%) by application of the kainate receptor selective antagonist, ACET (0.1-1 μM), but not by the AMPA receptor selective antagonist, GYKI 53655 (10 μM). Control recordings from horizontal cells showed that glutamate-evoked currents were blocked by GYKI 53655 (n = 4), but not ACET (n = 6). OFF bipolar types showed evidence of kainate receptor heterogeneity, with differences in: response kinetics to agonist application, sensitivity to ACET, and immunohistochemical expression of the GluK1 receptor subunit. Finally, we found that ACET reversibly blocked light-evoked spiking in OFF midget and OFF parasol ganglion cells (n = 5 cells each), but had no effect on the corresponding ON ganglion cell types (n = 5 ON parasol, n = 3 ON midget). Voltage-clamp recordings revealed that ACET blocked light-evoked excitatory input to OFF ganglion cells without altering ON-pathway mediated crossover inhibition (n = 4 OFF parasol, n = 4 OFF midget).
Conclusions:
The results demonstrate that kainate receptors mediate synaptic transmission from cones to all OFF cone bipolar cell types in the macaque retina.
Keywords: 435 bipolar cells •
531 ganglion cells •
616 neurotransmitters/neurotransmitter systems