European Journal of Neuroscience, Vol. 8, pp. 2459-2466, 1996 @ European Neuroscience Association C. Aivadulla1, A. Aodriguez, S. Martinez-Conde, C. Acuña and J. Cudeiro1 Laboratorios de Neurociencia y Computación Neuronal (Unidad asociada al C.S.I.C, Instituto Cajal), Complejo Hospitalario Universitario, Universidad de Santiago de Compostela, Spain 1Dept. De Ciencias de la Salud I (E.U. Fisioterapia) and Unidad de Cirugía Experimental (Neurofisiología Visual), Hospital Juan Canalejo, Coruña, Spain Keywords: visual system, PGN, corticofugal, neuromodulation, parabrachial, spindle waves, sleep-wake cycle Abstract We have tested the effect of iontophoretic application of the nitric oxjde synthase inhibitor L-nitroarginine on the activity of a population of 53 perigeniculate (PGN) cells, recorded extracellularly in the anaesthetized paralysed cat. In all cells tested with visual stimulation during L-nitroarginine application (n = 15), the visually elicited responses were markedly reduced, on average by 63 :!: 15%, and there was a reduction in spontaneous activity too. This effect was blocked by co-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 donor S-nitroso-N-acetylpenicillamine (SNAP) elevated both visual responses and spontaneous discharge, an effect also seen with a second nitric oxjde donor, sodium nitroprusside (n = 12). The nitrjc oxjde synthase inhibitor L-nitroarginine was applied to a sub-population of seven cells and it selectively decreased NMDA mediated excitation (reduction 80 :!: 14%) with little or no effect on the excitation mediated by a-amino-3- hydroxy-5-5-methyl-4-isoxazole-propionic acjd (AMPA) or quisqualate (effects not statistically signifjcant), and it had no effect (n = 7) on excitation mediated by the metabotropic agonist (1 S,3R)-1-amjnocyclopentane-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-njtric oxide (DEA-NO) enhanced the actions of NMDA without an effect on responses to AMPA. These effects are qualitatively and quantitatively similar to those we have previously described for X and y type cells in the dorsallateral geniculate nucleus (dLGN), despjte the known opposjte effects of acetylcholine (ACh) application in the dLGN and PGN (ACh is co-Iocalized with nitric oxide synthase at both sites). We propose that within the PGN nitrjc oxide acts to enhance transmission utilizing NMDA receptors selectively (thereby interacting with the globally inhibiting effect of ACh at this sjte) to enhance vísual responses, reducing or removjng the non-specific inhibitory drive from PGN to dLGN seen in the spindling activity of slow-wave sleep. These effects will act in concert with the facilitatory actions of both ACh and nitric oxide within the dLGN proper, and will thereby enhance the faithful transmission of visual information from retina to cortex. Introduction The perigeniculate nucleus (PGN), the visual component of the thalamic reticular nucleus, is a major extrinsic source of GABAergic innervation to the dorsallateral geniculate nucleus (dLGN). The cells in the PGN have been shown to be immunoreactive for GABA, and they send their axons back into the thalamus, innervating both relay cells and local GABAergic intemeurons (Fitzpatrick et al., 1984; Montero and Singer, 1984; Rinvik et al.,1987). The PGN receives visual input both from collaterals of dLGN relay cells (Ahlsen et al., 1978; Ferster and LeVay, 1978; Friedlander et al., 1981; Ahlsen and Lindstrom, 1982) and from collaterals of the dense descending corticofugal projection to the dLGN (Updyke, 1975, 1977; Boyapati and Henry,1984; Robson, 1984). This pattem of connectivitv allows PGN cells to mediate the recurrent inhibition previously shown to operate on dLGN relay cells (Singer and Bedworth, 1973; Dubin and Cleland, 1977; Lindstrom, 1982). In addition, PGN cells receive a number of non-visual modulatory inputs, including cholinergic fibres from the paiabrachial region of the brainstem, which also innervate the dLGN (Kimura et al., 1981; Ahlsen and Lo, 1982; DeLima and Singer, 1987; Steriade et al., 1987; Bickford et al., 1993; Funke and Eysel,1993). Pharmacological investigations have demonstrated that acetyl- choline (ACh) markedly increases the discharge rate of dLGN relay cells, while PGN cells, like the intrinsic inhibitory intemeurons within the dLGN, are inhibited (Ben Ari et al., 1976; Godfraind. 1978: Correspondence to: Dr I. Cudeiro, E.U. Fisioterapia, Hospital Juan Canalejo, As Xubias 84, 15006 A Coruña, Spain Received 12 December 1995, revised 22 March 1996, accepted 21 June 1996