THE INFLUENCE OF NITRIC-OXIDE ON PERIGENICULATE GABAERGIC CELL-ACTIVITY IN THE ANESTHETIZED CAT

We have tested the effect of iontophoretic application of the nitric o xide synthase inhibitor L-nitroarginine on the activity of a populatio n of 53 perigeniculate (PGN) cells, recorded extracellularly in the an aesthetized paralysed cat. In all cells tested with visual stimulation during L-nitroarginine application (n = 15), the visually elicited re sponses were markedly reduced, on average by 63 +/- 15%, and there was a reduction in spontaneous activity too. This effect was blocked by c o-application of the substrate for nitric oxide synthase, L-arginine, but not by the inactive D-isoform, although application of L-arginine alone was without effect. Pressure application of the nitric oxide don or S-nitroso-N-acetylpenicillamine (SNAP) elevated both visual respons es and spontaneous discharge, an effect also seen with a second nitric oxide donor, sodium nitroprusside (n = 12). The nitric oxide synthase inhibitor L-nitroarginine was applied to a sub-population of seven ce lls and it selectively decreased NMDA mediated excitation (reduction 8 0 +/- 14%) with little or no effect on the excitation mediated by a-am ino-3-hydroxy-5-5-methyl-4-isoxazole-propionic acid (AMPA) or quisqual ate (effects not statistically significant), and it had no effect (n = 7) on excitation mediated by the metabotropic agonist (1S,3R)-1-amino cyclopentane-1,3-dicarboxylic acid (ACPD). Furthermore, application of SNAP also increased the magnitude of excitatory responses mediated by NMDA receptors. On a different population of seven cells, application of the new NO donor diethylamine-nitric oxide (DEA-NO) enhanced the a ctions of NMDA without an effect on responses to AMPA. These effects a re qualitatively and quantitatively similar to those we have previousl y described for X and Y type cells in the dorsal lateral geniculate nu cleus (dLGN), despite the known opposite effects of acetylcholine (ACh ) application in the dLGN and PGN (ACh is co-localized with nitric oxi de synthase at both sites). We propose that within the PGN nitric oxid e acts to enhance transmission utilizing NMDA receptors selectively (t hereby interacting with the globally inhibiting effect of ACh at this site) to enhance visual responses, reducing or removing the non-specif ic inhibitory drive from PGN to dLGN seen in the spindling activity of slow-wave sleep. These effects will act in concert with the facilitat ory actions of both ACh and nitric oxide within the dLGN proper, and w ill thereby enhance the faithful transmission of visual information fr om retina to cortex.