Nitric Oxide Production in Rat Thalamus Changes with Behavioral State, Local Depolarization, and Brainstem Stimulation

Since its discovery as a putative neurotransmitter in the CNS, several functional roles have been suggested for nitric oxide (NO). However, few studies have investigated the role of NO in natural physiology. Because NO synthase (NOS) has been localized in regions believed to be important for attention and arousal, we hypothesized that NO production would be state-dependent. To test this hypothesis, we used in vivo microdialysis, coupled with the hemoglobin-trapping technique, to monitor extracellular NO concentrations in rat thalamus during wake, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. The thalamus is known to receive a massive innervation from the NOS/cholinergic neurons in the mesopontine brainstem, which have been suggested to play a key role in EEG desynchronized states. To test whether thalamic NO output was sensitive to neuronal-dependent changes in the mesopontine brainstem, we measured thalamic NO concentration in response to electrical stimulation in the laterodorsal tegmentum (LDT) of anesthetized rats. Finally, the calcium dependence of NO release was tested by local depolarization with a high potassium dialysate or by addition of a calcium chelator. The results showed that (1) extracellular NO concentrations in the thalamus were high during wake and REM sleep and significantly lower during SWS, (2) thalamic NO release increased in response to LDT stimulation in both a site-specific and tetrodotoxin (TTX)-dependent manner, and (3) NO production was calcium-dependent. These data suggest that thalamic NO production may play a role in arousal.

[1]  M. Miyazaki,et al.  Possible release of nitric oxide from cholinergic axons in the thalamus by stimulation of the rat laterodorsal tegmental nucleus as measured with voltammetry , 1996, Journal of Chemical Neuroanatomy.

[2]  M. R. Dzoljic,et al.  Sleep and nitric: oxide: effects of 7-nitro indazole, inhibitor of brain nitric oxide synthase , 1996, Brain Research.

[3]  M. Jouvet,et al.  [Voltametric detection of cerebral NO in rats. Variations of the signal throughout the sleep-wakefulness cycle]. , 1996, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[4]  L. Martinez,et al.  Further Observations on the Role of Nitric Oxide in the Feline Lateral Geniculate Nucleus , 1996, The European journal of neuroscience.

[5]  K. Edelstein,et al.  Distribution of NADPH-diaphorase staining and light-induced fos expression in the rat suprachiasmatic nucleus region supports a role for nitric oxide in the circadian system , 1995, Neuroscience.

[6]  M. Gillette,et al.  Nitric oxide synthase inhibitor blocks light-induced phase shifts of the circadian activity rhythm, but not c-fos expression in the suprachiasmatic nucleus of the Syrian hamster , 1995, Brain Research.

[7]  R. Lydic,et al.  Nitric oxide synthase inhibition decreases pontine acetylcholine release , 1995, Neuroreport.

[8]  T. Nishikawa,et al.  Extracellular concentration of endogenous free d-serine in the rat brain as revealed by in vivo microdialysis , 1995, Neuroscience.

[9]  S. Vincent,et al.  Molecular Characterization of a Type II Cyclic GMP‐Dependent Protein Kinase Expressed in the Rat Brain , 1995, Journal of neurochemistry.

[10]  N. Tashiro,et al.  The effect of phencyclidine on the basal and high potassium evoked extracellular GABA levels in the striatum of freely-moving rats: an in vivo microdialysis study , 1995, Brain Research.

[11]  C D Marsden,et al.  Increased striatal dopamine efflux in vivo following inhibition of cerebral nitric oxide synthase by the novel monosodium salt of 7‐nitro indazole , 1995, British journal of pharmacology.

[12]  M. Gillette,et al.  Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. , 1994, Science.

[13]  J. Krueger,et al.  Inhibition of nitric oxide synthesis inhibits rat sleep , 1994, Brain Research.

[14]  J. Wood,et al.  Models of the diffusional spread of nitric oxide: Implications for neural nitric oxide signalling and its pharmacological properties , 1994, Neuropharmacology.

[15]  G. Nisticó,et al.  Evidence that Nitric Oxide Is Involved in the Control of Electrocortical Arousal , 1994, Annals of the New York Academy of Sciences.

[16]  S. Vincent,et al.  Brain heme oxygenase isoenzymes and nitric oxide synthase are co-localized in select neurons , 1994, Neuroscience.

[17]  R. McCarron,et al.  L‐arginine induces dopamine release from the striatum in vivo , 1994, Neuroreport.

[18]  M. R. Dzoljic,et al.  Nitric oxide synthase inhibition reduces wakefulness , 1994, Neuropharmacology.

[19]  U. Walter,et al.  Cloning, expression, and in situ localization of rat intestinal cGMP-dependent protein kinase II. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[20]  H. Fibiger,et al.  State-dependent release of acetylcholine in rat thalamus measured by in vivo microdialysis , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  J. Lancaster,et al.  Simulation of the diffusion and reaction of endogenously produced nitric oxide. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Tamura,et al.  Dynamic features of hemodynamic and metabolic changes in the human brain during all-night sleep as revealed by near-infrared spectroscopy , 1994, Brain Research.

[23]  Y. Kayama,et al.  Regulation of regional blood flow in the laterodorsal thalamus by ascending cholinergic nerve fibers from the laterodorsal tegmental nucleus , 1994, Neuroscience Research.

[24]  K. Fuxe,et al.  Facilitation of gaba release by neurotensin is associated with a reduction of dopamine release in rat nucleus accumbens , 1994, Neuroscience.

[25]  K. E. Binns,et al.  Release of the nitric oxide precursor, arginine, from the thalamus upon sensory afferent stimulation, and its effect on thalamic neurons in vivo , 1994, Neuroscience.

[26]  C. Nathan,et al.  Regulation of biosynthesis of nitric oxide. , 1994, The Journal of biological chemistry.

[27]  Paul Leonard Gabbott,et al.  An oriented framework of neuronal processes in the ventral lateral geniculate nucleus of the rat demonstrated by NADPH diaphorase histochemistry and GABA immunocytochemistry , 1994, Neuroscience.

[28]  K. Kendrick,et al.  Modulation of In Vivo Striatal Transmitter Release by Nitric Oxide and Cyclic GMP , 1994, Journal of neurochemistry.

[29]  M. Raiteri,et al.  Extracellular cGMP in the hippocampus of freely moving rats as an index of nitric oxide (NO) synthase activity , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  E. Leung,et al.  Nitric oxide-dependent efflux of cGMP in rat cerebellar cortex: an in vivo microdialysis study , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  T. Maher,et al.  Determination of Kainic Acid‐Induced Release of Nitric Oxide Using a Novel Hemoglobin Trapping Technique with Microdialysis , 1993, Journal of neurochemistry.

[32]  Paul Leonard Gabbott,et al.  Histochemical localization of nadph-dependent diaphorase (nitric oxide synthase) activity in vascular endothelial cells in the rat brain , 1993, Neuroscience.

[33]  D. Lorrain,et al.  Nitric oxide increases dopamine and serotonin release in the medial preoptic area , 1993, Neuroreport.

[34]  G. Nisticó,et al.  Inhibition by Nω‐nitro‐L‐arginine methyl ester of the electrocortical arousal response in rats , 1993 .

[35]  S. Snyder,et al.  Carbon monoxide: a putative neural messenger. , 1993, Science.

[36]  P. Klatt,et al.  Regulation of Neuronal Nitric Oxide and Cyclic GMP Formation by Ca2+ , 1992, Journal of neurochemistry.

[37]  G. Kojda,et al.  Spectrophotometric determination of nitric oxide using hemoglobin , 1992 .

[38]  K. Johnson,et al.  Nitric oxide induces neurotransmitter release from hippocampal slices. , 1992, European journal of pharmacology.

[39]  H. Pape,et al.  Nitric oxide controls oscillatory activity in thalamocortical neurons , 1992, Neuron.

[40]  R. Berne,et al.  Competitive inhibition of nitric oxide synthase prevents the cortical hyperemia associated with peripheral nerve stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[41]  O. Inanami,et al.  Nitric oxide (NO) is involved in increased cerebral cortical blood flow following stimulation of the nucleus basalis of Meynert in anesthetized rats , 1992, Neuroscience Letters.

[42]  H. Kimura,et al.  Histochemical mapping of nitric oxide synthase in the rat brain , 1992, Neuroscience.

[43]  E. Jodo,et al.  Firing of ‘possibly’ cholinergic neurons in the rat laterodorsal tegmental nucleus during sleep and wakefulness , 1992, Brain Research.

[44]  E. Kandel,et al.  Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[45]  D. Madison,et al.  A requirement for the intercellular messenger nitric oxide in long-term potentiation. , 1991, Science.

[46]  H. Sies,et al.  Nitric oxide production by cultured aortic endothelial cells in response to thiol depletion and replenishment. , 1991, The Journal of biological chemistry.

[47]  K. Shibuki,et al.  Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum , 1991, Nature.

[48]  G Oakson,et al.  Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  Richard Graham Knowles,et al.  Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[50]  H. Heller,et al.  Arousal state vs. temperature effects on neuronal activity in subcoeruleus area. , 1989, The American journal of physiology.

[51]  L. Ignarro.  Endothelium‐derived nitric oxide: actions and properties , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[52]  J. Garthwaite,et al.  Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain , 1988, Nature.

[53]  B. Wainer,et al.  Ascending projections from the pedunculopontine tegmental nucleus and the adjacent mesopontine tegmentum in the rat , 1988, The Journal of comparative neurology.

[54]  M. Maines,et al.  Evidence suggesting that the two forms of heme oxygenase are products of different genes. , 1988, The Journal of biological chemistry.

[55]  L. Ignarro,et al.  Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[56]  J. M. Crowder,et al.  Continuous glutamate leakage from brain cells is balanced by compensatory high-affinity reuptake transport , 1987, Neuroscience Letters.

[57]  M. Feelisch,et al.  Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. , 1987, European journal of pharmacology.

[58]  S. Moncada,et al.  Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor , 1987, Nature.

[59]  H. Fibiger,et al.  Cholinergic neurons of the laterodorsal tegmental nucleus: Efferent and afferent connections , 1986, The Journal of comparative neurology.

[60]  Larry L. Butcher,et al.  Cholinergic systems in the rat brain: III. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain , 1986, Brain Research Bulletin.

[61]  H. Fibiger,et al.  Neuropeptides and nadph-diaphorase activity in the ascending cholinergic reticular system of the rat , 1986, Neuroscience.

[62]  M. Maines,et al.  Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. , 1986, The Journal of biological chemistry.

[63]  A. C. Cuello,et al.  Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry , 1985, Brain Research.

[64]  H. Fibiger,et al.  NADPH-diaphorase: A selective histochemical marker for the cholinergic neurons of the pontine reticular formation , 1983, Neuroscience Letters.

[65]  H. Wada,et al.  Changes in the levels of cyclic nucleotides in rat brain during the sleep-wakefulness cycle , 1981, Brain Research.

[66]  Q. Gibson,et al.  Conformation, co-operativity and ligand binding in human hemoglobin. , 1975, Journal of molecular biology.

[67]  Bradley E. Copeland,et al.  Spectrophotometry of Haemoglobin Derivatives , 1971 .

[68]  C. Shute,et al.  The ascending cholinergic reticular system: neocortical, olfactory and subcortical projections. , 1967, Brain : a journal of neurology.

[69]  H. Dixon,et al.  Reduction of Methaemoglobin in Haemoglobin Samples using Gel Filtration for Continuous Removal of Reaction Products , 1967, Nature.

[70]  M. Jouvet,et al.  Détection voltamétrique du NO cérébral chez le rat. Variations du signal à travers le cycle veille-sommeil , 1996 .

[71]  M E Murphy,et al.  Nitric oxide assay using hemoglobin method. , 1994, Methods in enzymology.

[72]  E. Rüther,et al.  Relationship between cerebral blood flow velocities and cerebral electrical activity in sleep. , 1994, Sleep.

[73]  Michael E. P. Murphy,et al.  [24] Nitric oxide assay using hemoglobin method , 1994 .

[74]  M. Feelisch.  The Biochemical Pathways of Nitric Oxide Formation from Nitrovasodilators: Appropriate Choice of Exogenous NO Donors and Aspects of Preparation and Handling of Aqueous NO Solutions , 1991 .

[75]  B. Westerink,et al.  A microdialysis and automated on-line analysis approach to study central cholinergic transmission in vivo , 1991 .

[76]  S. Snyder,et al.  Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[77]  E. G. Jones,et al.  Thalamic oscillations and signaling , 1990 .

[78]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[79]  G. Moruzzi,et al.  Brain stem reticular formation and activation of the EEG. , 1949, Electroencephalography and clinical neurophysiology.