The network-selective actions of quinoxalines on the neurocircuitry operations of the rabbit retina.
We examined the contribution of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxalole-4-propionic acid (AMPA)/kainate (KA) receptors to the light-responses of rabbit retinal neurons. In the outer retina, bath application of the AMPA/KA receptor antagonists 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and 2,3,dihydroxy-6-nitro-7-sulfamoyl-benzo-f-quinoxaline (NBQX) blocked the light-responses of horizontal cells. Application of quinoxalines enhanced ON-bipolar cell light-responses, and was associated with a hyperpolarization of their resting potentials. In the inner retina, application of both AMPA/KA and NMDA antagonists to AII amacrine-like cells only partially blocked their light-responses. Their residual responses may reflect electrical coupling to neighboring ON-center cone bipolar cells, and can inhibit OFF-center ganglion cells. ON-sustained ganglion cells were highly sensitive to the quinoxalines, which reduced their light-evoked firing, while the firing of ON-transient cells remained as NMDA-mediated light-responses. Quinoxalines had differential effects on the firing rates of ON- and OFF-center ganglion cells: ON-cells were reduced, while OFF-cells were increased. In contrast, firing rates of ON-OFF ganglion cells were not excited by NBQX, and showed a recovered light-response mediated by NMDA receptors. The receptive field surround was lost in ganglion cells. For comparison, NMDA antagonists had only moderate effects on all ganglion cell light-responses. Our results indicate that NMDA and AMPA/KA receptors both contribute to ganglion cell light-responses. However, AMPA/KA receptors also significantly effect the light-response of neurons presynaptic to retinal ganglion cells, altering the observed pharmacology at the ganglion cell level.
Cohen
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Department of Physiology, University of Minnesota, 435 Delaware Street, Minneapolis, MN 55455, USA. ethan.cohen@yale.edu
Miller
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D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009415:Nerve Net / Q000187:drug effects* / Q000528:radiation effects; D011810:Quinoxalines / Q000494:pharmacology*; D011817:Rabbits; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000528:radiation effects; D012160:Retina / Q000187:drug effects* / Q000528:radiation effects / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000528:radiation effects; D014795:Visual Pathways / Q000187:drug effects* / Q000528:radiation effects / Q000648:ultrastructure; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C056723:FG 9041; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid