The role of excitatory amino acid (EAA) receptors in primate retinal ganglion cell function was analyzed in a superfused retina-eyecup preparation using single-unit, extracellular recording techniques. The effects of bath applied L-2-amino-4-phosphonobutyrate (APB), N-methyl-D-aspartate (NMDA), and non-NMDA EAA receptor agonists and antagonists were examined on the light-evoked responses and resting firing rates of ganglion cells. APB (30-100 jxM) reduced or blocked the light-evoked responses and resting firing rates of all ON-center ganglion cells; higher doses of APB (100 jxM) were required to block the light-evoked responses of ON-transient cells. In contrast, an increase in resting firing rates was observed when L-APB was applied to some OFF-center ganglion cells. The EAA agonists kainate (KA) (10-20 AM) and NMDA (200-350 /am) increased the firing rate of virtually all ganglion cells examined. Quisqualate (10-20 /xM) increased firing in most cells, but occasionally (4/13 cases) produced inhibition. The NMDA antagonist D-amino-phosphono-heptanoic acid (D-AP7) (200-250 ^M) reduced the light-evoked responses of ganglion cells by an average of 12% from control levels, while resting firing rates declined 37%. In the presence of D-AP7, the basic receptive-field characteristics of cells were not significantly altered. In contrast, two non-NMDA receptor antagonists, NBQX (2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxalinedione) and DNQX (6,7-dinitro-quinoxaline-2,3-dione), produced substantial reductions in the light-evoked responses (82%) and resting firing rates (87%) of all ganglion cell classes. A striking observation in some neurons was the recovery of a persistent transient light-evoked response in the presence of NBQX. This NBQX-insensitive, light-evoked response was always blocked by adding D-AP7. Thus, neurotransmission from bipolar to ganglion cells in primates is mediated predominantly by non-NMDA EAA receptors, with NMDA receptors forming a minor component of the light-evoked response.
Bibliographical noteFunding Information:
The authors wish to thank Drs. Chip Bowman; Robert Morstad; the University of Minnesota, Department of Ophthalmology; and especially Dr. Tim Ebner for tissue donations. We thank Dr. Tag Honore (A/S Ferrosan CNS Div., Soeborg, Denmark) for his gift of NBQX, and Carol Toris for technical assistance during the first series of experiments. We thank David Marshak and Stan Schein for helpful discussions. This research was supported by NIH funding F32 EY06171 to Ethan D. Cohen and R01 EY03014 to Robert F. Miller.
- Excitatory amino acid receptors
- Ganglion cells
- Primate retina