Advertisement

Cholinergic Plasticity and the Meaning of Death

  • Michael McKinney
  • Karen Baskerville
  • David Personett
  • Katrina Williams
  • John Gonzales

Abstract

The selective degeneration of basal forebrain cholinergic neurons in several major human brain diseases has been known now for several decades, but why these cells die is still a puzzle. Our research addressing mechanisms of selective cholinergic vulnerability is structured by a hypothesis of multiple insults, one of which is oxidative stress. In our rodent model of aging, we have obtained convincing evidence that brain oxidative stress is associated with cognitive decline. The age-related oxidative stress may be global in nature, and probably includes effects on cholinergic neurons. This chapter first describes the anatomy and physiology of several major central cholinergic populations. We then summarize how we are using multiple models and experimental approaches to address how these populations might differ with respect to their vulnerability to oxidative stress, in particular nitrosative stress. The discussion is placed within the context of recent technological developments in brain research involving microarray screening of gene expression. Several examples are given to show how these technologies can be applied to discovery of neuronal signaling pathways likely to be important in human disease conditions. Finally, we outline some of the ways we are employing these methods in studies of the vasculature of the brain to address issues in stroke biology.

Keywords

Nitric Oxide Nitric Oxide Cholinergic Neuron Basal Forebrain Cholinergic System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agnati, L.F., Bjelke, B., and Fuxe, K. (1995) Volume versus wiring transmission in the brain: a new theoretical frame for neuropsychopharmacology. Medicinal Res. Rev. 15: 33–45.Google Scholar
  2. Alarcon-Vargas, D. and Ronai, Z. (2002) p53-Mdm2-the affair that never ends. Carcinogen 23: 541–547.Google Scholar
  3. Alter, O., Brown, P.O., and Botstein, D. (2000) Singular value decomposition for genome-wide expression data processing and modeling. Proc. Natl. Acad. Sci. USA 97: 10101–10106.PubMedGoogle Scholar
  4. Alonso, J.R. and Amaral, D.G. (1995) Cholinergic innervation of the primate hippocampal formation I. Distribution of choline acetyltransferase immunoreactivity in the Macaca fascicularis and Macaca mulatta monkeys. J. Comp. Neurol. 355: 135–170.PubMedGoogle Scholar
  5. Amaral, D. G. and Witter, M.P. (1995) Hippocampal Formation IN The Rat Nervous System. (2nd edition). Ed. G. Paxinos, Academic Press, San Diego, pp, 443–486.Google Scholar
  6. Apparsundaram, S., Ferguson, S.M., George, A.L., and Blakely, R.D. (2000) Molecular cloning of a human, hemicholinium-3-sensitive choline transporter. Biochem. Biophys, Res. Comm. 276: 862–867.Google Scholar
  7. Arriagda, P.V., Growdon, J.H., Hedley-Whyte, E.T., and Hyman, B.T. (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer s disease. Neurol. 42: 631–699.Google Scholar
  8. Bai, X.-C., Deng, F., Liu, A.-L., Zou, Z.-P., Wang, Y., Ke, Z.-Y., Ji, Q.-S., and Luo, S.-Q. (2002) Phospholipae C-g1 is required for cell survival in oxidative stress by protein kinase C. Biochem. J. 363: 395–401.PubMedGoogle Scholar
  9. Ballif, B.A. and Blenis, J. (2001) Molecular mechanisms mediating mammalian mitogenactivated protein kinase (MAPK) kinase (MEK)-MAPK cell survival signals. Cell Growth & Diff. 12: 397–408.Google Scholar
  10. Bartus, R.T., Dean, R.L., Beer, B., and Lippa, A.S. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417.PubMedGoogle Scholar
  11. Baxter, M.G. and Chiba, A.A. (1999) Cognitive functions of the basal forebrain. Curr. Opinion Neurobiol. 9: 178–183.Google Scholar
  12. Baxter, M.G., Bucci, D.J., Sobel, T.J., Williams, M.J., Gorman, L.K., and Gallagher, M. (1996a) Intact spatial learning following lesions of basal forebrain cholinergic neurons. NeuroReport 7: 1417–1420.PubMedGoogle Scholar
  13. Baxter, M.G., Bucci, D.J., Gorman, L.K., Wiley, R.G., and Gallagher, M. (1996b) Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats. Behav. Neurosci. 109: 714–722.Google Scholar
  14. Baxter, M.G., Bucci, DJ., Holland, P.C., and Gallagher, M. (1999) Impairments in conditioned stimulus processing and conditioned responding after combined selective removal of hippocampal and neocortical cholinergic input. Behav. Neurosci. 113: 486–495.PubMedGoogle Scholar
  15. Baxter, J.G., Holland, P.C., and Gallagher, M. (1997) Disruption of decrements in conditioned stimulus processing by selective removal of hippocampal cholinergic input. J. Neurosci. 17: 5230–5236.PubMedGoogle Scholar
  16. Baxter, M.G. and Gallagher, M. (1996) Intact spatial learning in both young and aged rats following selective removal of hippocampal cholinergic input. Behav. Neurosci. 110: 460–467.PubMedGoogle Scholar
  17. Bayraktar, T., Staiger, J.F., Acsady, L., Cozzari, C., Freund, T.F., and Zilles, K. (1997) Co-localization of vasoactive intestinal polypeptide, gamma-aminobutyric acid and choline acetyltransferase in neurocortical interneurons of the adult rat. Brain Res. 757: 209–217.PubMedGoogle Scholar
  18. Benzing, W.C., Ikonomovic, M.D., Brady, D.R., Mufson, E.J., and Armstrong, D.M. (1993) Evidence that transmitter-containing dystrophic neurites precede paired helical filament and Alz-50 formation within senile plaques in the amygdala of nondemented elderly and patients with Alzheimer’s disease J. Comp. Neurol. 334: 176–191.PubMedGoogle Scholar
  19. Behrens, M.I., Koh, J.Y., Muller, M.C., and Choi, D.W. (1996) NADPH diaphorase-containing striatal or cortical neurons are resistant to apoptosis. Neurobiol. Dis. 3: 72–75.PubMedGoogle Scholar
  20. Bertorelli, R., Forloni, G., and Consolo, S. (1991) Modulation of cortical in vivo acetylcholine release by the basal nuclear complex: a role of the pontomesencephalic tegmental area. Brain Res. 563: 353–356.PubMedGoogle Scholar
  21. Blaker, S.N., Armstrong, D.M., and Gage, F.H. (1988) Cholinergic neurons within the rat hippocampus: response to fimbria-fornix transection. J. Comp. Neurol. 272: 127–138.PubMedGoogle Scholar
  22. Blokland, A. (1996) Acetylcholine: a neurotransmitter for learning and memory? Brain Res. Rev. 21: 285–300.Google Scholar
  23. Boegman, R.J. and Parent, A. (1988) Differential sensitivity of neuropeptide Y, somatostatin and NADPH-diaphorase containing neurons in rat cortex and striatium to quinolinic acid. Brain Res. 445: 358–362.PubMedGoogle Scholar
  24. Bogdan, C. (2001) Nitric oxide and the regulation of gene expression. Trends Cell Biol. 11: 66–75.PubMedGoogle Scholar
  25. Boncristiano, S., Calhoun, M.E., Kelly, P.H., Pfeifer, M., Bondolfi, L., Stalder, M., Phinney, A.L., Abramowski, D., Sturchler-Pierrat, C., Enz, A., Sommer, B., Staufenbiel, M., and Jucker, M., (2002) Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. J. Neurosci. 22: 3234–2343.PubMedGoogle Scholar
  26. Bowen, D.M., Smith, C.B., White, P., and Davison, A.N. (1976) Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 99: 459–496.PubMedGoogle Scholar
  27. Brashear, H.R., Zaborszsky, L., and Heimer, L. (1986) Distribution of GABAergic and cholinergic neurons in the rat diagonal band. Neurosci. 17: 439–451.Google Scholar
  28. Browne, S.E., Lin, L., Mattson, A., Georgievska, B., and Isacson, O. (2001) Selective antibody-induced cholinergic cell and synapse loss produce sustained hippocampal and cortical hypometabolism with correlated cognitive deficits. Exp. Neurol. 170: 36–47.PubMedGoogle Scholar
  29. Bredt, D.S., Hwang, P.M., and Snyder, S.H. (1990) Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347: 768–770.PubMedGoogle Scholar
  30. Capsoni, S., Ugolini, G., Comparini, A., Ruberti, F., Berardi, N., and Cattaneo, A. (2000) Alzheimer-like neurodegeneration in aged anti-nerve growth factor transgenic mice. Proc. Natl. Acad. Sci. USA 97: 6826–6831.PubMedGoogle Scholar
  31. Carlsen, J. and Heimer, L. (1986) A correlated light and electron microscopic immunocytochemical study of cholinergic terminals and neurons in the rat amygdaloid body with special emphasis on the basolateral amygdaloid nucleus. J. Comp. Neurol. 244: 121–136.PubMedGoogle Scholar
  32. Carroll, J.D., Green, P.E., and Chaturvedi, A. (1997) Mathematical Tools for Applied Multivariate Analysis. 2nd ed. Academic Press, San Diego.Google Scholar
  33. Celesia, G.C., and Jasper, H.H. (1966) Acetylcholine released from cerebral cortex in relation to state of activation. Neurol. 16: 466–467.Google Scholar
  34. Clarke, D.J. (1985) Cholinergic innervation of the rat dentate gyrus: an immunocytochemical and electron microscopical study. Brain Res. 360: 349–354.PubMedGoogle Scholar
  35. Clarke, D.J. and Dunnett, S.B. (1986) Ultrastructural organization of cholineacetyltransferase-immunoreactive fibres innervating the neocortex from embryonic ventral forebrain grafts. J. Comp. Neurol. 250: 192–205.PubMedGoogle Scholar
  36. Coyle, J.T., Price, D.L., and DeLong, M.R. (1983) Alzheimer s disease: a disorder of cortical cholinergic innervation. Science 219:1184–1190.PubMedGoogle Scholar
  37. Cullen, K.M. and Halliday, G.M. (1998) Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurbiol. Aging 19: 297–306.Google Scholar
  38. Datta, S. (1997) Cellular basis of ontine ponto-geniculo-occipital wave generation and modulation. Cell. Mol. Neurobiol. 17: 341–365.PubMedGoogle Scholar
  39. Datta, S. and Siwek, D.F. (1997) Excitation of the brain stem pedunculopontine tegmentum cholinergic cells induces wakefulness and REM sleep. J. Neurophysiol. 77: 2975–2988.PubMedGoogle Scholar
  40. Datta, S.R., Brunet, A., and Greenberg, M.E. (1999) Cellular survival: a play in three Akts. Genes Dev. 13: 2905–2927.PubMedGoogle Scholar
  41. Davies, P. and Maloney, AJ.F. (1976) Selective loss of central cholinergic neurons in Alzheimer s disease. Lancet 2: 1403.PubMedGoogle Scholar
  42. Dawson, V.L. and Dawson, T.M. (1996) Nitric oxide neurotoxicity. J. Chem. Neuroanat. 10: 179–190.PubMedGoogle Scholar
  43. Dawson, V.L., Kizushi, V.M., Huang, P.L., Snyder, S.H., and Dawson, T.M. (1996) Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice. J. Neurosci. 16:2479–2487.PubMedGoogle Scholar
  44. Deora, A.A., Win, T., Vanhaesebroeck, B., and Lander, H.M. (1998) A redox-triggered Ras-effector interaction. J. Biol. Chem. 273: 29923–29928.PubMedGoogle Scholar
  45. De Lima, A.D. and Singer, W. (1986) Cholinergic innervation of the cat striate cortex: a choline acetyltransferase immunocytochemical analysis. J. Comp. Neurol. 250: 324–338.PubMedGoogle Scholar
  46. DeLong, M.R. (1971) Activity of pallidal neurons during movement. J. Neurophysiol. 34: 414–427.PubMedGoogle Scholar
  47. De Smaele, E., Zazzeroni, F., Papa, S., Nguyen, D.U., Jin, R., Jones, J., Cong, R., and Franzoso, G. (2001) Induction of gadd45b by NF-kB downregulates pro-apoptotic JNK signaling. Nature 414: 308–313.PubMedGoogle Scholar
  48. Detari, L., Rasmusson, D.D., and Semba, K. (1999) The role of basal forebrain neurons in tonic and phasic activation of the cerebral cortex. Prog. Neurobiol. 58: 249–277.PubMedGoogle Scholar
  49. Detari, L., Semba, K., and Rasmusson D.D. (1997) Responses of cortical EEG-related basal forebrain neurons to brainstem and sensory stimulation in urethane-anaesthetized rats. Eur. J. Neurosci. 9: 1153–1161.PubMedGoogle Scholar
  50. Diez, M., Koistinaho, J., Kahn, K., Games, D., and Hokfe1t, T. (2000) Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein — initial observations. Neurosci. 100: 259–286.Google Scholar
  51. Drachman, D.A. and Leavitt, J. (1974) Human memory and the cholinergic system. A relationship to aging? Arch. Neurol. 30: 113–121.PubMedGoogle Scholar
  52. Dringenberg, J.C. and Vanderwolf, C.H. (1997) Neocortical activation: modulation by multiple pathways acting on central cholinergic and serotonergic systems. Exp. Brain Res. 116: 160–174.PubMedGoogle Scholar
  53. Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M.N., Holcomb, L., Refolo, L., Zenk, B., Hardy, J., and Younkin, S. (1996) Increased amyloid-beta42(43 in brains of mice expressing mutant presenilin 1. Nature 383: 710–713.PubMedGoogle Scholar
  54. Dutar, P., Bassant, M.-H., Senut, M.-C., and Lamour Y. (1995) The septohippocampal pathway: structure and function of a central cholinergic system. Physiol. Rev. 75: 393–427.PubMedGoogle Scholar
  55. Eckenstein, F. and Baughman, R.W. (1984) Two types of cholinergic inervation in cortex, one co-localized with vasoactive intestinal polypeptide. Nature 309: 153–15.PubMedGoogle Scholar
  56. Eckenstein, F. and Thoenen, H. (1983) Cholinergic neurons in the rat cerebral cortex demonstrated by immunohistochemical localization of choline acetyltransferase. Neurosci. Lett. 36: 211–215.PubMedGoogle Scholar
  57. Everitt, B.J. and Robbins, T.W. (1997) Central cholinergic systems and cognition. Ann. Rev. Psychol. 48: 649–684.Google Scholar
  58. Eisen, M.B., Spellman, P.T., Brown, P.O., and Botstein, D. (1998) Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95: 14863–14868.PubMedGoogle Scholar
  59. Fass, U., Panickar, K., Personett, D., Bryan, D., Williams, K., Gonzales, J., Sugaya, K., and McKinney, M. (2000) Differential vulnerability of primary cultured cholinergic neurons to nitric oxide excess. NeuroReport 11: 931–936.PubMedGoogle Scholar
  60. Ferrante, R.J., Kowal, N.W., Beal, M.F., Richardson, E.P., Bird, E.D., and Martin, J.B. (1985) Selective sparing of a class of striatal neurons in Huntington’s disease. Science 230: 561–563.PubMedGoogle Scholar
  61. Fibiger, H.C. and Vincent, S.R. (1987) Anatomy of central cholinergic neurons. IN Psychopharmacology: The Third Generation of Progress. Ed. H.Y. Meltzer. New York, Raven Press, pp. 211–218.Google Scholar
  62. Fine, A. Hoyle, C., Maclean, C.J., Levatte, T.L., Baker, H.F., and Ridley, R.M. (1997) Learning impairments following injection of a selective cholinergic immunotoxin, ME20.4 IgG-saporin, into the basal nucleus of Meynert in monkeys. Neurosci. 81: 331–343.Google Scholar
  63. Fischer, S.J., McDonald, E.S., Gross, L., and Windebank, A.J. (2001) Alterations in cell cycle regulation underlie cysplatin induced apoptosis of dorsal root ganglion neurons in vivo. Neurobiol. Dis. 8: 1027–1035.PubMedGoogle Scholar
  64. Fisher, R.S., Buchwald, N.A., Hull, C.D., and Levine, M.S. (1988) GABAergic basal forebrain neurons project to the neocortex: the localization of glutamic acid decarboxylase and choline acetyltransferase in feline corticopetal neurons. J. Comp. Neurol. 272: 489–502.PubMedGoogle Scholar
  65. Frotscher, M. and Leranth, C. (1985) Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: a combined light and electron microscopic study. J. Comp. Neurol. 239: 237–246.PubMedGoogle Scholar
  66. Frotscher, M., Schlander, M., and Leranth, C. (1986) Cholinergic neurons in the hippocampus. A combined light-and electron-microscopic immunocytochemical study in the rat. Cell & Tiss. Res. 246: 293–301.Google Scholar
  67. Frotscher, M., Vida, I., and Bender, R. (2000) Evidence for the existence of non-GABAergic, cholinergic interneurons in the rodent hippocampus. Neurosci. 96:27–31.Google Scholar
  68. Fujita, N., Sato, S., Ishida, A., and Tsuruo, T. (2002) Involvement of HSP90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem. 277: 10346–10353.PubMedGoogle Scholar
  69. Furey, M.L., Pietrini, P., Haxby, J.V., Alexander, G.E., Lee, H.C., VanMeter, J., Grady, C.L., Shetty, U., Rapoport, S.I., Schapiro, M.B., and Freo, U. (1997) Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory. Proc. Natl. Acad. Sci. USA 94: 6512–6516.PubMedGoogle Scholar
  70. Gaykema, R.P., Gaal, G., Traber, J., Hersh, L.B., and Luiten, P.G. (1991) The basal forebrain cholinergic system: efferent and afferent connectivity and long-term effects of lesions. Acta Psych. Scand. Suppl. 466: 14–26.Google Scholar
  71. Gaspar, P., Duyckaerts, C., Febvret, A., Benoit, R., Beck, B., and Berger, B. (1989) Subpopulations of somatostatin 28-immunoreactive neurons display different vulnerability in senile dementia of the Alzheimer type. Brain Res. 490: 1–13.PubMedGoogle Scholar
  72. Gau, J.T., Steinhilb, M.L., Kao, T.C., D’Amato, C.J., Gaut, J.R., Frey, K.A. and Turner, R.S. (2002) Stable beta-secretase activity and presynaptic cholinergic markers during progressive central nervous system amyloidogenesis in Tg2576 mice. Am. J. Pathol. 160: 409–411.Google Scholar
  73. Geula, C., Schatz, C.R., and Mesulam, M.-M. (1993) Differential localization of NADPH-diaphorase and calcindin-D28K within the cholinergic neurons of the basal forebrain, striatum, and brainstem of the rat, monkey, baboon, and human. Neurosci. 54: 461–476.Google Scholar
  74. Golub, G.H. and van Loan, C.F. (1996) Matrix Computations. 3rd ed. Johns Hopkins University Press, Baltimore.Google Scholar
  75. Gonzalez-Zulueta, M., Ensz, L.M., Mukhina, G., Lebovitz, R.M., Zwacka, R.M., Engelhardt, J.F., Oberley, L.W., Dawson, V.L., and Dawson, T.M. (1998) Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide-mediated neurotoxicity. J. Neurosci. 18: 2040–2055.PubMedGoogle Scholar
  76. Gonzalez-Zulueta, M., Feldman, A.B., Klesse, L.J., Kalb, R.G., Dillman, J.F., Parada, L.F., Dawson, T.M., and Dawson, V.L. (2000) Requirement for nitric oxide activation of p21ras/extracellular regulated kinase in neuronal ischemic preconditioning. Proc. Natl. Acad. Sci. 97: 436–441.PubMedGoogle Scholar
  77. Gutierrez, H., Gutierrez, R., Ramirez-Trejo, L., Silva-Gandarias, R., Ormsby, C.E., Miranda, M.I., and Bermudez-Rattoni, F. (1999a) Redundant basal forebrain modulation in taste aversion memory formation. J. Neurosci. 19: 7661–7669.PubMedGoogle Scholar
  78. Gutierrez, H., Gutierrez, R., Silva-Gandarias, R., Estrada, J., Miranda, M.I., and Bermudez-Rattoni, F. (1999b) Differential effects of 192IgG-saporin and NMDA-induced lesions into the basal forebrain on cholinergic activity and taste aversion memory formation. Brain Res. 834: 136–141.PubMedGoogle Scholar
  79. Hallanger, A.E., Levey, A.I., Lee, H.I., Rye, D.B., and Wainer, B.H. (1987) The origins of cholinergic and other subcortical afferents to the thalamus in the rat. J. Comp. Neurol. 262: 105–124.PubMedGoogle Scholar
  80. Hallanger, A.E. and Wainer, B.H. (1988) Ascending projections from the pedunculopontine tegmental nucleus and the adjacent mesopontine tegmentum in the rat. J. Comp. Neurol. 274: 483–515.PubMedGoogle Scholar
  81. Hammond, D.N., Wainer, B.H., Tonsgard, H.J., and Heller, A. (1986) Development and characterization of clonal cell lines derived from septal cholinergic neurons. Science 234: 1237–1240.PubMedGoogle Scholar
  82. Hernandez, D., Sugaya, K., Qu, T., McGowan, E., Duff, K., and McKinney, M. (2001) Survival and plasticity of basal forebrain cholinergic systems in mice transgenic for presenilin-1 and amyloid precursor protein mutant genes. NeuroReport 12: 1377–1384.PubMedGoogle Scholar
  83. Hess, G., Donoghue, J.P. (1999) Facilitation of long-term potentiation in layer II/III horizontal connections of rat motor cortex following layer I stimulation: route of effect and cholinergic contributions. Exp. Brain Res. 127:279–290.PubMedGoogle Scholar
  84. Holcomb, L., Gordon, M.N., McGowan, E., Yu, X., Benkovic, S., Jantzen, P., Wright, K., Eckman, C., Younkin, S., Hsiao, K., and Duff, K. (1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nature Med. 4: 97–100.PubMedGoogle Scholar
  85. Holter, N.S., Mitra, M., Maritan, A., Cieplak, M., Banavar, JR., and Fedoroff, N.V. (2000) Fundamental patterns underlying gene expression profiles: simplicity to complexity. Proc. Natl. Acad. Sci. USA 79: 8409–8414.Google Scholar
  86. Hoover, D.B. and Jacobowitz, D.M. (1979) Neurochemical and histochemical studies of the effect of a lesion of the nucleus cuneiformis on the cholinergic innervation of discrete areas of the rat brain. Brain Res. 170: 113–122.PubMedGoogle Scholar
  87. Houser, C.R. (1990) Cholinergic synapses in the central nervous system: studies of the immunocytochemical localization of choline acetyltransferase. J. Elect. Micros. Tech. 15: 219.Google Scholar
  88. Houser, C.R., Crawford, G.D., Salvaterra, P.M., and Vaughn, J.E. (1985) Immunocytochemical localization of choline acetyltransferase in the rat cerebral cortex: a study of cholinergic neurons and synapses. J. Comp. Neurol. 234: 17–34.PubMedGoogle Scholar
  89. Hreib, K.K., Rosene, D.L., and Moss, M.B. (1988) Basal forebrain efferents to the medial dorsal thalamic nucleus in the rhesus monkey. J. Comp. Neurol. 277: 365–390.PubMedGoogle Scholar
  90. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., and Cole, G. (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274: 99–102.PubMedGoogle Scholar
  91. Hyman, B.T., Marzloff, K., Wenniger, J.J., Dawson, T.M., Bredt, D.S., and Snyder, S.H. (1992) Relative sparing of nitric oxide synthase-containing neurons in the hippocampal formation in Alzheimer s disease. Ann. Neurol. 32: 818–820.PubMedGoogle Scholar
  92. Impey, S., Obrietan, K., and Storm, D.R. (2000) Making new connections: role of ERKIMAP kinase signaling in neuronal plasticitiy. Neuron 23: 11–14.Google Scholar
  93. Ino, H. and Chiba, T. (2001) Cyclin-dependent kinase 4 and cyclin D1 are required for excitotoxin-induced neuronal cell death in vivo. J. Neurosci. 21: 6086–6094.PubMedGoogle Scholar
  94. Ichikawa, T and Hirata, Y. (1986) Organization of choline acetyltransferase-containing structures in the forebrain of the rat. J. Neurosci. 6: 281–292.PubMedGoogle Scholar
  95. Inglis, W.L. and Semba, K. (1997) Discriminable excitotoxic effects of ibotenic acid, AMPA, NMDA and quinolinic acid in the rat laterodorsal tegmental nucleus. Brain Res. 755: 17–27.PubMedGoogle Scholar
  96. Ischiropoulos, H. (1998) Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species. Arch. Biochem. Biophys. 356: 1–11.PubMedGoogle Scholar
  97. Inglis, W.L. and Senba, K. (1997) Discriminable excitotoxic effects of ibotenic acid, AMPA, NMDA, and quinolinic acid in the lateral dorsal tegmental nucleus. Brain Res. 755: 17–27.PubMedGoogle Scholar
  98. Jaffar, S., Counts, S.E., Ma, S.Y., Dadko, E., Gordon, M.N., Morgan, D., and Mufson, E.J. (2001) Neuropathology of mice carrying mutant APP(Swe) and/or PSI (M146L) transgenes: alterations in the p75 (NTR) cholinergic basal forebrain septohippocampal pathway. Exp. Neurol. 170: 227–243.PubMedGoogle Scholar
  99. Johnston, M.V., McKinney, M., and Coyle, J.T. (1979) Evidence for a cholinergic projection to neocortex from neurons in basal forebrain. Proc. Natl. Acad. Sci. USA 76: 5392–5396.PubMedGoogle Scholar
  100. Johnston, M.V., McKinney, M., and Coyle, J.T. (1981) Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rat. Exp. Brain Res. 43: 159–172.PubMedGoogle Scholar
  101. Kanai, T. and Szerb, J.C. (1965) Mesencephalic reticular activating system and cortical acetylcholine output. Nature 205: 80–82, 1965.PubMedGoogle Scholar
  102. Kelly, P.H. and Moore, K.E. (1978) Decrease of neocortical choline acetyltransferase after lesion of the globus pallidus in the rat. Exp. Neurol. 61: 479–484.PubMedGoogle Scholar
  103. Kent, C., Sugaya, K., Bryan, D., Personett, D., and McKinney, M. (1998) Expression of superoxide dismutase messenger RNA in adult rat brain cholinergic neurons. J. Mol. Neurosci. 12: 1–10.Google Scholar
  104. Kessler, J., Markowitsch, H.J., and Sigg, O. (1986) Memory related role of the posterior cholinergic system. Int. J. Neurosci. 30: 101–119.PubMedGoogle Scholar
  105. Kitt, C.A., Price, D.L., Struble, R.O., Cork, L.C., Wainer, B.H., Becher, M.W., and Mobley, W.C. (1984) Evidence for cholinergic neurites in senile plaques. Science 226:1443–1445.PubMedGoogle Scholar
  106. Klein, S.D. and Brune, B. (2002) Heat-shock protein 70 attenuates nitric oxide-induced apoptosis in RAW macrophages by preventing cytochrome c release. Biochem. J. 362: 635–641.PubMedGoogle Scholar
  107. Koh, J.Y. and Choi, D.W. (1988) Vulnerability of clutured cortical neurons to damage by excitotoxins: differential susceptibility of neurons containing NADPH-diaphorase. J. Neurosci. 8: 2153–2163.PubMedGoogle Scholar
  108. Kohler, C., Chan-Palay, V. and Wu, J.Y. (1984) Septal neurons containing glutamic acid decarboxylase immunoreactivity project to the hippocampal region in the brain. Anat. Embryol. 169: 41–44.PubMedGoogle Scholar
  109. Kowall, N.W. and Beal, M.F. (1988) Cortical somatostatin, neuropeptide Y, and NADPH diaphorase neurons: normal anatomy and alterations in Alzheimer’s disease Ann. Neurol. 23: 105–114.PubMedGoogle Scholar
  110. Lander, H.M., Hajjar D.P., Hempstead, RL., Mirza, U.A., Chait, RT., Campbell, S., and Quilliam, L.A. (1997) A molecular redox switch on p21ras. Structural basis for the nitric oxide-p2lras interaction. J. Biol. Chem. 272: 4323–4326.PubMedGoogle Scholar
  111. Lander, H.M., Ogiste, J.S., Teng, K.K., and Novogrodsky, A. (1995) p21ras as a common signaling target of reactive free radicals and cellular redox stress. J. Biol. Chem. 270: 21195–21198.PubMedGoogle Scholar
  112. Lehmann, J. Nagy, J.I., Atmadja, S., and Fibiger, H.C. (1980) The nucleus basalis magnocellularis: the origin of a cholinergic projection to the neocortex of the rat. Neurosci. 5: 1161–1174.Google Scholar
  113. Leranth, C. and Frotscher, M. (1987) Cholinergic innervation of hippocampal OAD-and somatostatin-immunoreactive commissural neurons. J. Comp. Neurol. 261: 33–47.PubMedGoogle Scholar
  114. Levey, A.I., Hallagher, A.E., and Wainer, B.H. (1987) Cholinergic nucleus basalis neurons may influence the cortex via the thalamus. Neurosci. Lett. 74: 7–13.PubMedGoogle Scholar
  115. Levey, A.I., Wainer, RH., Rye, D.B., Mufson, E.J., and Mesulam, M.M. (1984) Choline acetyltransferase-immunoreactive neurons intrinsic to rodent cortex and distinction from acetylcholinesterase-positive neurons. Neurosci. 13: 341–353.Google Scholar
  116. Lewis, P.R. and Shute, C.C.D. (1967) The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfomical organ and supra-optic crest. Brain 90: 521–540.PubMedGoogle Scholar
  117. Lewis, P.R., Shute, C.C.D., and Silver, A. (1967) Confirmation from choline acetylase analyses of a massive cholinergic innervation to the rat hippocampus. J. Physiol. 191: 215–224.PubMedGoogle Scholar
  118. Li, Z., Lin, H., Zhu, Y., Wang, M., and Luo, J. (2001) Disrupt ion of cell cycle kinetics and cyclin-dependent kinase system by ethanol in cultured cerebellar granule progenitors. Dev. Brain Res. 132: 47–58.Google Scholar
  119. Li, H. and Shen, X. (2000) Selective loss of basal forebrain cholinergic neurons in APP770 transgenic mice. Chin. Med. J. 113: 1040–1042.PubMedGoogle Scholar
  120. Lo Conte, G., Casamenti, F., Bigl, V., Milaneschi, E., and Pepeu, G. (1982) Effect of magnocellular forebrain nuclei lesions on acetylcholine output from the cerebral cortex, electrocorticogram and behavior. Arch. Ital. De Biol. 120: 176–188.Google Scholar
  121. Marshall, H.E., Merchant, K., and Stamler, J.S. (2000) Nitrosation and oxidation in the regulation of gene expression. FASEB J. 14: 18889–1900.Google Scholar
  122. Martinez-Serrano and Bjorklund, A. (1998) Ex vivo nerve growth factor gene transfer to the basal forebrain in presymptomatic middle-aged rats prevents the development of cholinergic neuron atrophy and cognitive impairment during aging. Proc. Natl. Acad. Sci. USA 95: 1858–1863.PubMedGoogle Scholar
  123. Masliah, E., Rockenstein, E., Veinbergs, I., Sagara, Y., Mallory, M., Hashimoto, M., and Mucke, L. (2001) Beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer’s disease and Parkinson’s disease Proc. Natl. Acad. Sci. USA 98: 12245–12250.PubMedGoogle Scholar
  124. Matsumura, M.E., Lobe, D.R., and McNamara, C.A. (2002) Contribution of the helix-loop-helix factor Id2 to regulation of vascular smooth muscle cell proliferation. J. Biol. Chem. 277: 7293–7297.PubMedGoogle Scholar
  125. Matthews, D.A., Salvaterra, P.M., Crawford, G.D., Houser, C.R., and Vaughn, J.E. (1987) An immunocytochemical study of choline acetyltransferase-containing neurons and axon terminals in normal and partially deafferented hippocampal formation. Brain Res. 402: 30–43.PubMedGoogle Scholar
  126. Mayo, L.D. and Bonner, D.B. (2001) A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc. Natl. Acad. Sci. USA 98: 11598–11603.PubMedGoogle Scholar
  127. McGowan, E., Sanders, S., Iwatsubo, T., Takeuchi, A., Saido, T., Zehr, C., Yu, X., Uljon, S., Wang, R., Mann, D., Dickson, D., and Duff, K. (1999) Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol. Dis. 6: 231–244.PubMedGoogle Scholar
  128. McLin, D.E., Miasnikov, A.A., and Weinberger, N.M. (2002) Induction of behavioral associative memory by stimulation of the nucleus basalis. Proc. Natl. Acad. Sci. USA 99: 4002–4007.PubMedGoogle Scholar
  129. McKinney, M. and Coyle, J.T. (1991) The potential for muscarinic receptor subtype-specific pharmacotherapy for Alzheimer’s disease. Mayo Clinic Proc. 66: 1225–1237.Google Scholar
  130. McKinney, M., Coyle, J.T., and Hedreen, J.C. (1983) Topographic analysis of the innervation of the rat neocortex and hippocampus by the basal forebrain cholinergic system. J. Comp. Neurol. 217: 103–121.PubMedGoogle Scholar
  131. McMillian M., Kong, L.-Y., Sawin, S.M., Wilson, B., Das, K., Hudson, P., Hong, J.-S., and Bing, G. (1995) Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures. Biochem. Biophys. Res. Comm. 215: 572–577.PubMedGoogle Scholar
  132. Melander, T., Hokfelt, T., and Rokaeus, A. (1986) Distribution of galaninlike immunoreactivity in the rat central nervous system. J. Comp. Neurol. 248: 475–517.PubMedGoogle Scholar
  133. Melander, T., Staines, W.A., Hokfelt, T. Rokaeus, A., Eckenstein, F., Salvaterra, P.M., and Wainer, B.H. (1985) Galanin-like immunoreactivity in cholinergic neurons of the septum-basal forebrain complex projecting to the hippocampus of the rat. Brain Res. 360: 130–138.PubMedGoogle Scholar
  134. Mesulam, M.-M. and Van Hoesen G.W. (1976) Acetylcholinesterase-rich projections from the basal forebrain of the rhesus monkey to neocortex. Brain Res. 109: 152–157.PubMedGoogle Scholar
  135. Mesulam, M.-M., Geula, C., Bothwell, M.A., and Hersch, L.B. (1989) Human reticular formation: cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons. J. Comp. Neurol. 281: 611–633.Google Scholar
  136. Mesulam, M.M., Hersh, L.B., Mash, D.C., Geula, C. (1992) Differential cholinergic innervation within functional subdivisions of the human cerebral cortex: a choline acetyltransferase study. J. Comp. Neurol. 318: 316–328.PubMedGoogle Scholar
  137. Mesulam, M.-M., Mufson, EJ., Wainer, B.H., and Levey, A.I. (1983) Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Chl-Ch6). Neurosci. 10: 1185–1201.Google Scholar
  138. Mesulam, M.-M., Volicer, L., Marquis, J.K., Mufson, E.J., and Green, R.C. (1986) Systematic regional differences in the cholinergic innervation of the primate cerebral cortex: distribution of enzyme activities and some behavioral implications. Ann. Neurol. 19: 144–151.PubMedGoogle Scholar
  139. Miranda, M.I. and Bermudez-Rattoni, F. (1999) Reversible inactivation of the nucleus basalis magnocellularis induces disruption of cortical acetylcholine release and acquisition, but not retrieval, of aversive memories. Proc. Natl. Acad. Sci. USA 96: 6478–6482.PubMedGoogle Scholar
  140. Mitchell, J.F. (1963) The spontaneous and evoked release of acetylcholine from the cerebral cortex. J. Physiol. 165: 98–116.PubMedGoogle Scholar
  141. Moruzzi, G. and Magoun, H. (1949) Brain stem reticular formation and activation of EEG. EEG Clin. Neurophysiol. 1: 455–473.Google Scholar
  142. Nandagopal, K., Dawson, T.M., and Dawson, V.L. (2001) Critical role for nitric oxide signaling in cardiac and neuronal ischemic preconditioning and tolerance. J. Pharmacol. Exp. Ther. 297: 474–478.PubMedGoogle Scholar
  143. Nicolle, M.M., Gonzalez, J., Sugaya, K., Baskerville, K.A., Bryan, D., Lund, K., Gallagher, M., and McKinney, M. (2001) Signatures of hippocampal oxidative stress in aged spatial leaming-impaired rodents. Neurosci. 107: 415–431.Google Scholar
  144. Oakman, SA, Faris, P.L., Cozzari, C., and Hartman, B.K. (1999) Characterizaion of the extent of pontomesencephalic cholinergic neurons’ projections to the thalamus comparison with projections to the thalamus: comparison with projections to midbrain dopaminergic groups. Neurosci. 94: 529–547.Google Scholar
  145. Okuda, T. and Haga, T. (2000) Functional characterization of the human high-affinity choline transporter. FEBS Lett. 484: 92–97.PubMedGoogle Scholar
  146. Okuda, T., Haga, T., Kanai, Y., Endou, H., Ishihara, T., and Katsura, I. (2000) Identification and characterization of the high-affinity choline transporter. Nature Neurosci. 3: 120–125.PubMedGoogle Scholar
  147. Pare, D., Steriade, M., Deschenes, M., and Bouhassira, D. (1990) Prolonged enhancement of anterior thalamic synaptic responsiveness by stimulation of a brainstem cholinergic group. J. Neurosci. 10: 20–33.PubMedGoogle Scholar
  148. Parnavelas, J.G., Kelly, W., Franke, E., and Eckenstein, F. (1986) Cholinergic neurons and fibres in the rat visual cortex. J. Neurocytol. 15: 329–336.PubMedGoogle Scholar
  149. Pepeu, G. and Mantegazzini, P. (1964) Midbrain hemisection: effect on cortical acetylcholine in the cat. Science 145: 1069–1070.PubMedGoogle Scholar
  150. Perry, E.K., Gibson, P.H., Blessed, G., Perry, R.H., and Tomlinson, B.E. (1977) Neurotransmitter enzyme abnormalities in senile dementia. J. Neurol. Sci. 34: 247–265.PubMedGoogle Scholar
  151. Personett, D., Sugaya, K., Hammond, D., Robbins, M., and McKinney, M. (1997) Use of capillary electrophoresis with laser-induced fluorescence detection to assess messenger ribonucleic acid molecules amplified by the polymerase chain reaction: applications in the cloning of cells. Electrophoresis 18: 1750–1759.PubMedGoogle Scholar
  152. Personett, D., Fass, U., Panickar, K., and McKinney, M. (2000) Retinoic acid-mediated enhancement of the cholinergic/neuronal nitric oxide synthase phenotype of the medial septal SN56 clone: establishment of a nitric oxide-sensitive proapoptotic state. J. Neurochem. 74: 2412–2424.PubMedGoogle Scholar
  153. Pfeilschifter, J., Eberhardt, W., and Beck, K.-F. (2001) Regulation of gene expression by nitric oxide. Pflugers Archiv-Eur J Physiol DOI 10.1007/s004240100586.Google Scholar
  154. Power, A.E., Thal, L.J., and McGaugh, J.L. (2002) Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block memory enhancement with posttraining norepinephrine in the basolateral amygdala. Proc. Natl. Acad. Sci. USA 99: 2315–2319.PubMedGoogle Scholar
  155. Ravagnan, L., Gurbuxani, S., Susin, S.A., Maisse, C., Daugas, E., Zamzami, N., Mak, T., Jaattela, M., Penninger, J.M., Garrido, C., and Kroemer, G. (2001) Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nature Cell Biol. 3: 839–843.PubMedGoogle Scholar
  156. Rasmusson, D.D., Clow, K., and Szerb, J.C. (1994) Modification of neocortical acetylchoine release and electroencephalogram desynchronization due to brainstem stimulation by drugs applied to the basal forebrain. Neurosci. 60: 665–677.Google Scholar
  157. Rebeck, G., Marzloff, K., and Hyman, B. (1993) The pattern of NADPH-diaphorase staining, a marker of nitric oxide synthase activity, is altered in the perforant pathway terminal zone in Alzheimer’s disease. Neurosci. Lett. 153: 165–168.Google Scholar
  158. Ridley, R.M., Barefoot, H.C., Maclean, C.J., Pugh, P., and Baker, H.F. (1999a) Different effects on learning ability after injection of the cholinergic immunotoxin ME20AlgG-saporin into the diagonal band of Broca, basal nucleus of Meynert, or both in monkeys. Behav. Neurosci. 113: 303–315.PubMedGoogle Scholar
  159. Ridley, R.M., Pugh, P., Maclean, C.J., and Baker, H.F. (1999b) Severe learning impairment caused by combined immunotoxic lesion of the cholinergic projections to the cortex and hippocampus in monkeys. Brain Res. 836: 120–138.PubMedGoogle Scholar
  160. Rye, D.B., Wainer, B.H., Mesulam, M.M., Mufson, EJ., and Saper, C.B. (1984) Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neurosci. 13: 627–643.Google Scholar
  161. Robner, S. (1997) Cholinergic imunolesions by 192IgG-saporin—A useful tool to simulate pathogenic aspects of Alzheimer’s disease. Int. J. Devl. Neurosci. 15: 835–850.Google Scholar
  162. Semba, K., Reiner, P.B., McGeer, E.G., and Fibiger, H.C. (1989) Brainstem projecting neurons in the rat basal forebrain: neurochemical, topographical, and physiological distinctions from cortically projecting cholinergic neurons. Brain Res. Bull. 22: 501–509.PubMedGoogle Scholar
  163. Senut, M.C., Menetrey, D., and Lamour, Y. (1989) Cholinergic and peptidergic projections from the medial septum and the nucleus of the diagonal band of Broca to dorsal hippocampus, cingulate cortex and olfactory bulb: a combined wheatgerm agglutininapohorseradish peroxidase-gold immunohistochemical study. Neurosci. 30: 385–403.Google Scholar
  164. Shute, C.C.C. and Lewis, P.R. (1967) The ascending cholinergic reticular system: neocortical, olfactory and subcortical projections. Brain 90: 497–520.PubMedGoogle Scholar
  165. Smiley, J.F. and Mesulam, M.-M. (1999) Cholinergic neurons of the nucleus basalis of Meynert receive cholinergic, catecholaminergic and GABAergic synapses: an electron microscopic investigation in the monkey. Neurosci. 88: 241–255, 1999.Google Scholar
  166. Smith, D.E., Roberts, J., Gage, F.H., and Tuszynski, M.H. (1999) Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proc. Natl. Acad. Sci. USA 96: 10893–10898.PubMedGoogle Scholar
  167. Stambolic, V., Mak, T.W., and Woodgett, J.R. (1999) Modulation of cellular apoptotic potential: contributions to oncogenesis. Oncogene 18: 6094–6103.PubMedGoogle Scholar
  168. Standaert, D.G., Saper, C.B., Rye, D.B., and Wainer, B.H. (1986) Colocalization of atriopeptin-like immunoreactivity with choline acetyltransferase-and substance P-like immunoreactivity in the pedunculopontine and laterodorsal tegmental nuclei in the rat. Brain Res. 382: 163–168.PubMedGoogle Scholar
  169. Steckler, T., Inglis, W., Winn, P., and Sahgal, A. (1994) The pedunculopontine tegmental nucleus: a role in cognitive processes? Brain Res. Rev. 19: 298–318.PubMedGoogle Scholar
  170. Stegh, A.H., Herrmann, H., Lampel, S., Weisenberger, D., Andra, K., Seper, M., Wiche, G., Krammer, P.H., and Peter, M.E. (2000) Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95-and tumor necrosis factor receptor-mediated apoptosis. Mol. Cell. Biol. 20: 5665–5679.PubMedGoogle Scholar
  171. Steriade, M. Amzica, F., and Nunez, A. (1993) Cholinergic and noradrenergic modulation of the slow (≈0.3 Hz) oscillation in neocortical cells. J. Neurophysiol. 70: 1385–1400.PubMedGoogle Scholar
  172. Stewart, D.J., MacFabe, D.F., and Vanderwolf, C.H. (1984) Cholinergic activation of the electrocorticogram: role of the substantia innominata and effects of atropine and quinuclidinyl benzilate. Brain Res. 322: 219–232.PubMedGoogle Scholar
  173. Struble, R.G., Powers, R.E., Casanova, M.F., Kitt, C.A., Brown, E.C., and Price, D.L. (1987) Neuropeptidergic systems in plaques of Alzheimer s disease. J. Neuropathol. & Exp. Neurol. 46: 567–584.Google Scholar
  174. Sturchler-Pierrat, C. and Staufenbiel, M. (2000) Pathogenic mechanisms of Alzheimer’s disease analyzed in the APP23 transgenic mouse model. Ann. N.Y. Acad. Sci. 920: 134–139.PubMedGoogle Scholar
  175. Sugaya, K. and McKinney, M. (1994) Nitric oxide synthase gene expression in cholinergic neurons in the rat brain examined by combined immunocytochemistry and in situ hybridization histochemistry. Mol. Brain Res. 23: 111–125.PubMedGoogle Scholar
  176. Szerb, J.C. (1967) Cortical acetylcholine release and electroencephalographic arousal. J. Physiol. 192: 329–343.PubMedGoogle Scholar
  177. Tao, L., Murphy, M.E.P., and English, A.M. (2002) S-nitrosation of Ca2+-1oaded and Ca2+-free recombinant calbindin D28K from human brain. Biochem. 41: 6185–6192.Google Scholar
  178. Tong, T., Fan, W., Zhao, H., Jin, S., Fan, F., Blanck, P., Alomo, I., Rajasekaran, B., Liu, Y., Holbrook, N.J., and Zhan, Q. (2001) Involvement of MAP kinase pathways in induction of GADD45 following UV radiation. Exp. Cell Res. 269: 64–72.PubMedGoogle Scholar
  179. Umbriaco, D., Garcia, S., Beaulieu, C., and Descarries, L. (1995) Relational features of acetylcholine, noradrenaline, serotonin and GABA axon terminals in the stratum radiatum of adult rat hippocampus (CAl). Hippocampus 5: 605–620.PubMedGoogle Scholar
  180. Umbriaco, D., Watkins, K.C., Descarries, L., Cozzari, C., and Hartman, B.K. (1994) Ultrastructural and morphometric features of the acetylcholine innervation in adult rat parietal cortex: an electron microscopic study in serial sections. J. Comp. Neurol. 348: 351–373.PubMedGoogle Scholar
  181. Unger, J.W. and Lange, W. (1992) NADPH-diaphorase-positive cell populations in the human amygdala and temporal cortex: neuroanatomy, peptidergic characteristics and aspects of aging and Alzheimer’s disease. Acta Neuropathol. 83: 636–646.PubMedGoogle Scholar
  182. Vanderwolf, C.H. (1975) Neocortical and hippocampal activation in relation to behavior: effects of atropine, eserine, phenothiazines and amphetamine. J. Comp. Physiol. Psychol. 88: 300–323.PubMedGoogle Scholar
  183. Vanderwolf, C.H. and Robinson, T.E. (1981) Reticulo-cortical activity and behavior: a critique of the arousal theory and a new synthesis. Behav. Brain Sci. 4: 459–514.Google Scholar
  184. Vanhaesebroeck, B. and Alessi, D.R. (2000) The PI3K-PDK1 connection: more than just a road to PKB. Biochem. J. 346: 561–576.PubMedGoogle Scholar
  185. Vincent, S.R. and Kimura, H. (1992) Histochemical mapping of nitric oxide synthase in the rat brain. Neurosci. 46: 755–784.Google Scholar
  186. Vincent, S.R., Satoh, K, Armstrong, D.M., and Fibiger, H.C. (1983a) Substance P in the ascending cholinergic reticular system. Nature 306: 688–691.PubMedGoogle Scholar
  187. Vincent, S.R., Satoh, K., Armstrong, D.M., and Fibiger, H.C. (1983b) NADPH-diaphorase: a selective histochemical marker for the cholinergic neurons of the pontine reticular formation. Neurosci. Lett. 43: 31–36.PubMedGoogle Scholar
  188. Vincent, S.R., Satoh, K., Armstrong, D.M., Panula, P., Vale, W., and Fibiger, H.C. (1986) Neuropeptides and NADPH-diaphorase activity in the ascending cholinergic reticular system of the rat. Neurosci. 17: 167–182.Google Scholar
  189. Vizi, E.S., Kiss, J.P. (1998) Neurochemistry and pharmacology of the major hippocampal transmitter systems: synaptic and nonsynaptic interactions. Hippocampus 8:566–607.PubMedGoogle Scholar
  190. Waite, J.J., Chen, A.D., Wardlow, M.L., Wiley, R.G., Lappi, D.A., and Thal, L.J. (1995) 192 immunoglobulin G-saporin produces graded behavioral and biochemical changes accompanying the loss of cholinergic neurons of the basal forebrain and cerebellar Purkinje cells. Neurosci. 65: 463–476.Google Scholar
  191. Waite, J.J. and Thal, L.J. (1996) Lesions of the cholinergic nuclei in the rat basal forebrain: excitotoxins vs. an immunotoxin. Life Sci. 58: 1947–1953.PubMedGoogle Scholar
  192. Wall, M.E., Dyck, P.A., and Brettin, T.S. (2001) SVDMAN-singular value decomposition of microarray data. Bioinformatics 17: 566–568.PubMedGoogle Scholar
  193. Walker, L.C., Price, D.L., and Young III, W.S. (1989) GABAergic neurons in the primate basal forebrain magnocellular complex. Brain Res. 499: 188–192.PubMedGoogle Scholar
  194. Wang, X.W., Vermeulen, W., Coursen, J.D., Gibson, M., Lupoid, S.E., Forrester, K., Xu, G., Elmore, L., Yeh, H., Hoeijmakers, J.H., and Harris, C.C. (1996) The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Genes & Devel. 10: 1219–1232.Google Scholar
  195. Wei, G., Dawson, V.L., and Zweier, J.L. (1999) Role of neuronal and endothelial nitric oxide synthase in nitric oxide generation in the brain following cerebral ischemia. Biochim. Biophys. Acta 1455: 23–34.PubMedGoogle Scholar
  196. Wenk, G.L. (1996) Neuroprotection and selective vulnerability of neurons within the nucleus basalis magnocellularis. Behav. Brain Res. 72: 17–24.Google Scholar
  197. Wenk, G.L. (1997) The nucleus basalis magnocellularis cholinergic system: one hundred years of progress. Neurobiol. Learn. Mem. 67: 85–95.PubMedGoogle Scholar
  198. Wenk, G.L. and Willard, L.B. (1998) The neural mechanisms underlying cholinergic cell death within the basal forebrain. Int. J. Dev. Neurosci. 16: 729–735.PubMedGoogle Scholar
  199. Wenk, H., Bigl, V., and Meyer, U., (1980) Cholinergic projections from magnocellular nuclei of the basal forebrain to cortical areas in rats. Brain Res. Rev. 2: 295–316.Google Scholar
  200. Whitehouse, P.J., Price, D.L., Struble, R.G., Clark, A.W., Coyle, J.T., and DeLong, M.R. (1982) Alzheimer s disease and senile dementia: loss of neurons in the basal forebrain. Science 215: 1237–1239.PubMedGoogle Scholar
  201. Winkler, J., Suhr, S.T., Gage, F.H., Thai, L.J., and Fisher, L.J. (1995) Essential role of neocortical acetylcholine in spatial memory. Nature 375: 484–487.PubMedGoogle Scholar
  202. Wisniowski, L., Ridley, R.M., Baker, H.F., and Fine, A (1992) Tyrosine hydroxylase-immunoreactive neurons in the nucleus basalis of the common marmoset (Callithrix jacchus). J. Comp. Neurol. 325: 379–387.PubMedGoogle Scholar
  203. Woolf, N.J, Jacobs, R.W., and Butcher, L.L. (1989) The pontomesencephalotegmental cholinergic system does not degernerate in Alzheimer’s disease. Neurosci. Lett, 96: 277–282.PubMedGoogle Scholar
  204. Wong, T.P., Debeir, T., Duff, K. and Cuello, A.C. (1999) Reorganization of cholinergic terminal in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes. J. Neurosci. 29: 2706–2716.Google Scholar
  205. Wrenn, C.C., Lappi, D.A., and Wiley, R.G. (1999) Threshold relationship between lesion extent of the cholinergic basal forebrain in the rat and working memory impairment in the radial maze. Brain Res. 847: 284–298.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Michael McKinney
    • 1
  • Karen Baskerville
    • 1
  • David Personett
    • 1
  • Katrina Williams
    • 1
  • John Gonzales
    • 1
  1. 1.Department of PharmacologyMayo ClinicJacksonvilleUSA

Personalised recommendations