Summary
Human visual cortex was studied using NADPH-diaphorase histochemistry and nitric oxide synthase immunohistochemistry. Large, strongly stained, sparsely spined non-pyramidal cells (average soma diameter: 16 × 16 μm) occur in layers H–VI, but are commonest in layers II–III. Small weakly stained multipolar cells (average soma diameter 3.6 × 4 μm, stellate like cells) in layers II–VI are concentrated in layer IV of areas 17 and 18. The density of these cells, measured with a computer assisted microscopy system is less in area 18 than 17. Large, strongly stained, predominantly horizontal cells (average soma diameter 12 × 19 μm) are localized in the underlying white matter. Axons of the large, strongly NADPH-diaphorase positive cells are thin and unbranched with fine boutons. These axons ascend to layer I. The large, strongly stained cells in layers II–VI we identify as Martinotti neurons. In layer I parallel unbranched positive fibres with some fine boutons run horizontally and build dense axonal plexuses together with the axons of Martinotti neurons. Axons of presumed extrinsic origin are morphologically different from NADPH-diaphorase positive intrinsic fibres. They show thick varicosities running in different directions and forming a network in layers III–VI. Basket like formations of these fibres were frequently observed in layers IV, V and VI. Other fibres seem to innervate blood vessels. Nitric oxide synthase was also demonstrated immunohistochemically by a polyclonal rabbit nitric oxide synthase antiserum. The morphology and distribution of the immunostained cells correspond with those seen with NADPH-diaphorase histochemistry. Double labelling experiments confirm the colocalization of NADPH-diaphorase and nitric oxide synthase in all demonstrated cells. Immunohistochemical demonstration of glial fibrillary acidic protein has shown that astrocytes are not involved in the NADPH-diaphorase/NOS system in the human visual cortex.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akbarian, S., Vinuela, A., Kim, J. J., Potkin, S. G., Bunney, W. E., Jr &Jones, E. G. (1993) Distorted distribution of nicotinamide-adenine dinucleotide phos-phate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development.Archives of General Psychiatry 50, 178–87.
Aoki, C., Fenstemaker, S., Lubin, M. &Go, C. G. (1993) Nitric oxide synthase in the visual cortex of monocular monkeys as revealed by light and electron microscopic immunocytochemistry.Brain Research 620, 97–113.
Beal, M. F. (1992) Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?Annals of Neurology 31, 119–30.
Bredt, D. S., Hwang, P. M. &Snyder, S. H. (1990) Localization of nitric oxide synthase indicating a neuronal role for nitric oxide.Nature 347, 768–70.
Bredt, D. S., Hwang, P. M., Glatt, C. E., Lowenstein, C., -Reed, R. R. &Snyder, S. H. (1991) Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase.Nature 351, 714–18.
Dawson, V. L., Dawson, T. M., London, E. D., Bredt, D. S. &Snyder, S. H. (1991) Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures.Proceedings of the National Academy of Sciences (USA) 88, 6368–71.
Defelipe, J. (1993) A study of NADPH diaphorase-positive axonal plexuses in the human temporal cortex.Brain Research 615, 342–6.
Egberongbe, Y. I., Gentleman, S. M., Falkai, P., Bogerts, B., Polak, J. M. &Roberts, G. W. (1994) The distribution of nitric oxide synthase immunoreactivity in the human brain.Neuroscience 59, 561–78.
Ellison, D. W., Kowall, N. W. &Martin, J. B. (1987) Subset of neurons characterized by the presence of NADPH-diaphorase in human substantia innominata.Journal of Comparative Neurology 260, 233–45.
Fairén, A., Defelipe, J. &Regidor, J. (1984) Nonpyramidal neurons: general account. InCerebral Cortex, vol. 1 (edited byPeters, A. &Jones, E. G.) pp. 201–45. New York and London: Plenum Press.
Ferriero, D. M., Arcavi, L. J., Sagar, S. M., Mcintosh, T. K. &Simon, R. P. (1988) Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia.Annals of Neurology 24, 670–6.
Gally, J. A., Montague, P. R., Reeke, G. N. &Edelman, G. M. (1990) The NO hypothesis: possible effects of a short-lived, rapidly diffusible signal in the development and function of the nervous system.Proceedings of the National Academy of Sciences (USA) 87, 3547–51.
Garthwaite, J. (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system.Trends in Neuroscience 14, 60–8.
Goadsby, P. J., Kaube, H. &Hoskin, K. L. (1992) Nitric oxide synthesis couples cerebral blood flow and metabolism.Brain Research 595, 167–70.
Hedlich, A., Lüth, H. J. &Seidel, J. (1990a) Spinefreie GABAerge Neuronen im visuellen Cortex der Ratte.Journal für Hirnforschung 31, 137–51.
Hedlich, A., Lüth, H. J., Werner, L., Bär, B., Hanisch, U. &Winkelmann, E. (1990b) GABAerge NADPH-diaphorase-positive Martinottizellen im visuellen Cortex der Ratte.Journal für Hirnforschung 31, 681–7.
Hope, B. T., Michael, G. J., Knigge, K. M. &Vincent, S. R. (1991) Neuronal NADPH-diaphorase is a nitric oxide synthase.Proceedings of the National Academy of Sciences (USA) 88, 2811–14.
Jacobs, W. R., Farivar, N. &Butcher, L. L. (1985) Alzheimer dementia and reduced nicotinamide adenine dinucleotide (NADH)-diaphorase activity in senile plaques and the basal forebrain.Neuroscience Letters 53, 39–44.
Johnson, M. D. &Ma, P. M. (1993) Localization of NADPH diaphorase activity in monoaminergic neurons of rat brain.Journal of Comparative Neurology 332, 391–406.
Knowles, R. G., Palacios, M., Palmer, R. M. J. &Mon-Cada, S. (1989) Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase.Proceedings of the National Academy of Sciences (USA) 86, 5159–62.
Koh, J. Y. &Choi, D. W. (1988) Vulnerability of cultured cortical neurons to damage by excitotoxins: differential susceptibility of neurons containing NADPH-diaphorase.Journal of Neuroscience 8, 2153–63.
Kowal, N. &Beal, M. F. (1988) Cortical somatostatin, neuropeptide Y and NADPH-diaphorase: normal anatomy and alterations in Alzheimer's disease.Annals of Neurology 23, 105–14.
Kummer, W., Fischer, A., Mundel, P., Mayer, B., Hoba, B., Philippin, B. &Preissler, U. (1992) Nitric oxide in VIP-containing vasodilator nerve fibres in the guinea pig.NeuroReport 3, 653–5.
Lund, J. S. (1984) Spiny stellate neurons. InCerebral Cortex, vol. 1 (edited byPeters, A. &Jones, E. G.) pp. 225–308. New York and London: Plenum Press.
Lüth, H. J. &Winkelmann, E. (1994) Immunohisto-chemische Charakterisierung von NO-Synthase positiven Nervenzellen im cerebralen Cortex des Menschen.Anatomischer Anzeiger Suppl. 176, 75.
Marin-Padilla, M. (1984) Neurons of layer I. A developmental analysis. InCerebral Cortex vol. 1 (edited byPeters, A. &Jones, E. G.) pp. 447–78. New York and London: Plenum Press.
Mayer, B., John, M. &Böhme, E. (1990) Purification of a Ca2+/calmodulin-dependent nitric oxide synthase from porcine cerebellum: cofactor role of tetrahydrobiopterin.FEBS Letters 277, 215–19.
Meyer, G., Wahle, P., Castaneyra-Perdomo, A. &Ferres-Torres, R. (1992) Morphology of neurons in the white matter of the adult human neocortex.Experimental Brain Research 88, 204–12.
Meyer, G. &González-Hernández, T. (1993) Developmental changes in layer I of the human neocortex during prenatal life: a Dil-tracing AChE and NADPH-d histo-chemistry study.Journal of Comparative Neurology 338, 317–36.
Sandell, J. H. (1986) NADPH Diaphorase histochemistry in the macaque striate cortex.Journal of Comparative Neurology 251, 388–97.
Schmidt, H. H. W., Gagne, C. D., Nakane, M., Pollock, J. S., Miller, M. F. &Murad, F. (1992a) Mapping of neuronal nitric oxide synthase in the rat suggests frequent colocation with NADPH-diaphorase but not soluble guanylyl cyclase and novel paraneural functions for nitricergic signal transduction.Journal of Histochemistry and Cytochemistry 40, 1439–56.
Schmidt, H. H. W., Smith, R. M., Nakane, M. &Murad, F. (1992b) Ca2+/calmodulin dependent NO synthase type I: Biopteroflavoprotein with Ca2+/calmodulin independent diaphorase and reductase activities.Biochemistry 31, 3243–9.
Schütz, Uy., Krahwinkel, A., Bloch, W., Addicks, K. &Schröder, H. (1994) Das neuronale NO-System des Cortex: Typisierung corticaler, NADPH-diaphorase positiver Neuronen bei Ratte und Maus.Anatomischer Anzeiger Suppl.176, 174–5.
Spessert, R., Layes, E. &Vollrath, L. (1994) Unterscheidung einer NOS-abhängigen und einer NOS-unabhängigen NADPH Diaphorase Färbung im Bulbus olfactorius der Ratte.Anatomischer Anzeiger Suppl.176, 188.
Thomas, E. &Pearse, A. G. E. (1961) The fine localization of dehydrogenases in the nervous system.Histochemie 2, 266–82.
Uemura, Y., Kowall, N. W. &Beal, M. F. (1990) Selective spearing of NADPH-diaphorase-somatos-tatin-neuropeptide Y neurons in ischemie gerbil striaturn.Annals of Neurology 27, 620–5.
Valtschanoff, J. G., Weinberg, R. J., Kharazia, V. N., Schmidt, H. W., Nakane, M. andRustioni, A. (1993) Neurons in rat cerebral cortex that synthesize nitric oxide: NADPH diaphorase histochemistry, NOS immunohistochemistry, and colocalization with GABA.Neuroscience Letters 57, 157–61.
Vincent, S. R. &Johansson, O. (1983) Striatal neurons containing both somatostatin- and avian pancreatic polypeptide (APP)-like immunoreactivities and NADPH-diaphorase activity: a light and electron microscopic study.Journal of Comparative Neurology 217, 264–70.
Vincent, S. R., Johansson, O., Hökfelt, T., Skirboll, L., Elde, R. P., Terenius, L., Kimmel, J. &Goldstein, M. (1983) NADPH-diaphorase: a selective histochemical marker for Striatal neurons containing both somatostatin and avian pancreatic polypeptide (APP)-like immunoreactivities.Journal of Comparative Neurology 217, 252–63.
Vincent, S. R. (1984) Neuropeptide coexistence in the mammalian forebrain. InCoexistence of Neuroactive Substances in Neurons (edited byChan-Palay, V. &Palay, S. L.) pp. 127–35. New York: John Wiley and Sons.
Vincent, S. R. (1986) NADPH-diaphorase histochemistry and transmitter coexistence. InNeurohistochemistry: Modern Methods and Applications (edited byPanula, PäivÄrinta, H. &Soinila, S.) pp. 375–96. New York: Alan R. Liss.
Vincent, S. R. &Hope, B. T. (1992) Neurons that say NO.Trends in Neuroscience 15, 108–13.
Vincent, S. R. &Kimura, H. (1992) Histochemical mapping of nitric oxide synthase in rat brain.Neuroscience 46, 755–84.
Yan, X. X., Garey, L. J. &Jen, L. S. (1994a) Development of NADPH-diaphorase activity in the rat neocortex.Developmental Brain Research 79, 29–38.
Yan, X. X., Jen, L. S. &Garey, L. J. (1994b) Neurons in primate cerebral cortex that synthesise nitric oxide: morphological diversity, differential distribution and colocalisation with GABA and calcium binding proteins. Submitted.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lüth, H.J., Hedlich, A., Hilbig, H. et al. Morphological analyses of NADPH-diaphorase/nitric oxide synthase positive structures in human visual cortex. J Neurocytol 23, 770–782 (1994). https://doi.org/10.1007/BF01268089
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01268089