Presynaptic Markers of Cholinergic Function in Cortex Following Ibotenic Acid Lesion of the Basal Forebrain

  • Martha Downen
  • Kimi Sugaya
  • Stephen P. Arneric
  • Ezio Giacobini
Part of the Advances in Behavioral Biology book series (ABBI, volume 36)


The large neurons of the magnocellular nucleus of the basal forebrain provide the maior extrinsic cholinergic innervation of the cerebral cortex1,2,3,4,5. The cells of origin form a diffusely localized cell group known as the nucleus basalis magnocellularis (NBM) and are found in the region of the ventromedial portion of the globus pallidus, the substantia innominata and the preoptic magnocellular nucleus. These cells send widespread projections to the cerebral cortex and the amygdala. This cell group is of particular interest given the finding that an analogous system in the human, known as the nucleus basalis of Meynert, shows considerable damage in Alzheimer’s Disease (AD)6• Lesions of the rat NBM provide an animal model that mimics some of the neurochemical pathology associated with AD.


Basal Forebrain Nucleus Basalis Neurochemical Pathology ChAT Activity Ibotenic Acid 
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  1. 1.
    Johnston, M. V., McKinney, M. & Coyle, J. T. (1981) Neocortical cholinergic innervation: A description of extrinsic and intrinsic components in the rat Exp. Br. Res. 43: 159–172.Google Scholar
  2. 2.
    Mesulam, M.-M., Mufson, E. J., Levey, A. I., and Wainer, B. H. (1983) Cholinergic innervation of cortex by the basal forebrain: Cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia inominata) and hypothalamus in the rhesus monkey. J. Comp. Neurol. 214: 170–197.Google Scholar
  3. 3.
    Saper, C. B. (1984) Organization of cerebral cortical afferent systems in the rat. II. Magnocellular basal nucleus. J. Comp. Neurol. 222: 313–342.Google Scholar
  4. 4.
    Shute, C. C. D. and Lewis, P. R. (1967) The ascending cholinergic reticular system: Neocortical, olfactory and subcortical projections. Brain 90: 497–520.Google Scholar
  5. 5.
    Rye, D. B., Wainer, B. H., Mesulam, M.-M., Mufson, E. J., and Saper, C. B. (1984) Cortical projections arising from the basal forebrain: A study of cholinergic and non-cholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neurosci. 13: 627–643.Google Scholar
  6. 6.
    Etienne, P., Robitaille, Y., Wood, P., Gauthier, S., Nair, N. P. V. and Quirion, R. (1986) Nucleus basalis neuronal loss, neuritic plaques and choline acetyltransferase activity in advanced Alzheimer’s Disease. Neurosci. 19: 1279–1291.CrossRefGoogle Scholar
  7. 7.
    Watson, M., Vickroy, T. W., Fibiger, H. C., Roeske, W. R. and Yamamura, H. I. (1985) Effects of bilateral ibotenate-induced lesions of the nucleus basalis magnocellularis upon selective cholinergic biochemical markers in the rat anterior cerebral cortex. Er. Res. 346: 387–391.Google Scholar
  8. 8.
    Pedata, F., Lo Conte, G., Sorki, S., Marconini-Pepeu, I., Pepeu, G. (1982) Changes in high-affinity choline uptake in rat cortex following lesions of the magnocellular forebrain nuclei Br. Res. 233: 359–367.CrossRefGoogle Scholar
  9. 9.
    Lo Conte, G., Casamenti, F., Bigl, V., Milaneschi, E., and Pepeu, G. (1982) Effect of magnocellular forebrain nuclei lesions on ACh output from the cerebral cortex, electrocorticogram and behavior. Arch. Ital. Biol. 120: 176–188.Google Scholar
  10. 10.
    Casamenti, F., Pedata, F., Sorki, S., LoConte, G. and Pepeu, G. (1981) Lesions of the globus pallidus: Changes in cortical ChAT, choline uptake and acetylcholine output in the rat. In: Cholinergic peripheral synapses. clinical significance. (Eds.: G. Pepeu and H. Ladinsky ), Plenum Publ. Comp., New York, pp. 685–694.Google Scholar
  11. 11.
    Bowen, D. M., Allen, S. J., Benton, J. S., Goodhardt, M. H., Haan, E. A., Palmer, A. M., Sims, N R., Smith, C. C. T., Spillane, J. A., Esiri, M. M., Neary, D., Snowdon, J. S., Wilcock, G. K., and Davison, A. N. (1983) Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer’s Disease. J. Neurochem 41: 266–272.CrossRefGoogle Scholar
  12. 12.
    Henke, H. and Lang, W. (1983) Cholinergic enzymes in neocortex, hippocampus and basal forebrain of non-neurological and senile dementia of Alzheimer-type patients. Br. Res. 267: 281–291.CrossRefGoogle Scholar
  13. 13.
    Nagai, T., McGeer, P. L., Peng, J. H., McGeer, E. G., and Dolman, C. E. (1983) Choline acetyltransferase immunohistochemistry in brains of Alzheimer’s disease patients and controls. Neurosci. Letters 36: 195–199.CrossRefGoogle Scholar
  14. 14.
    Perry, R. H., Candy, J. M., Perry, E. K. Irving, D., Blessed, G., Fairbairn, A. F., and Tomlinson, B. E. (1982) Extensive loss of choline acetyltransferase activity is not reflected by neuronal loss in the nucleus of meynert in Alzheimer’s disease. Neurosci. Letters 33: 311–315.CrossRefGoogle Scholar
  15. 15.
    Reisine, T. D., Yamamura, H. I., Bird, E. D., Spokes, E. and Enna, S. J. Pre-and postsynaptic neurochemical alterations in Alzheimer’s Disease. Br. Res. 159: 477–481.Google Scholar
  16. 16.
    Nilsson, L., Nordberg, A., Hardy, J., Wester, P., and Winblad, B. (1986) Physostigmine restores [3H]-acetylcholine efflux from Alzheimer brain slices to normal level. J. Neural Transm. 67: 275–285CrossRefGoogle Scholar
  17. 17.
    Sims, N. R., Bowen, D. M., Allen, S. J., Smith C. C. T., Nearry, D., Thomas, D. J. and Davison, A. N. (1983) Presynaptic cholinergic dysfunction in patients with dementia. J. Neurochem. 40: 503–509.CrossRefGoogle Scholar
  18. 18.
    Bartus, R. T., Dean, R. L., Pontecorvo, M. J., and Flicker, C. (1985) The cholinergic hypothesis: A historical overview, current perspective, and future directions. Annals N.Y. Acad. Sci. 444: 332–358.CrossRefGoogle Scholar
  19. 19.
    Wenk, G. and Olton, D. S. (1987) Basal forebrain cholinergic neurons and Alzheimer’s Disease. In: Animal Models of Dementia (ED.: Coyle, J. T.), Alan R. Liss, New York, pp. 81–101.Google Scholar
  20. 20.
    Salamone, J. D., Beart, P. M., Alpert, J. E. and Iverson, S. D. (1984) Impairment in T-maze reinforced alternation performance following nucleus basalis magnocellularis lesions in rats. Behay. Br. Res. 13: 63–70.CrossRefGoogle Scholar
  21. 21.
    Giacobini, E., DeSarno, P., Mcllhany, M., and Clark, B. (1988) In: Nicotinic Acetylcholine Receptors in the Nervous System. R. Clementi, C. Gotti, and E. Sher (Eds.)Series M, Cell bioloaY, NATO ASI series, vol M.25, P. 367–378. Springer Verlag.Google Scholar
  22. 22.
    Whitehouse, P. J., Martino, A. M., Antuono, P. G., Lowenstein, P. K., Coyle, J. T., Price, D. L. & Kellar, K. J. (1986) Nicotinic acetylcholine binding sites in Alzheimer’s Disease. Br. Res. 371: 146–151.CrossRefGoogle Scholar
  23. 23.
    Meyer, E. M., Arendash, G. W., Judkins, J. H., Ying, L., Wade, C. and Kem, W. R. (1987) Effects of nucleus basalis lesion on the muscarinic and nicotinic modulation of [3H]-acetylcholine release the rat cerebral cortex. J. Neurochem. 49: 1758–1762.CrossRefGoogle Scholar
  24. 24.
    Atack, J. R., Wenk, G. L., Wagster, M. V., Kellar, K. J., Whitehouse, P. J., and Rapoport, S. I. (1989) Bilateral changes in neocortical [3H]pirenzepine and [3H]oxotremorine-M binding following unilateral lesions of the rat nucleus basalis magnocellularis: an autoradiographic study. Br. Res. 483: 367–372.CrossRefGoogle Scholar
  25. 25.
    Wenk, G. L. and Rokaeus, A. (1988) Basal forebrain lesions differentially alter galanin levels and acetylcholinergic receptors in the hippocampus and neocortex. Br. Res. 460: 17–21.CrossRefGoogle Scholar
  26. 26.
    Gardiner, I. M., deBelleroche, J., Premi, B. K., and Hamilton, M. H. (1987) Effect of lesion of the nucleus basalis of rat on ACh release in cerebral cortex: time course of compensatory events. Br. Res. 407: 263–271.CrossRefGoogle Scholar
  27. 27.
    Mufson, E. J., Kehr, A. D., Wainer, B. H. and Mesulam, M.-M. (1987) Cortical effects of neurotoxin damage to the nucleus basalis in rats: persistent loss of extrinsic cholinergic input and lack of transsynaptic effect upon the number of somatostatin-containing, cholinesterase-positive and cholinergic cortical neurons. Br. Res. 417: 385–388.CrossRefGoogle Scholar
  28. 28.
    Wenk, G. L. and Olton, D. S. (1984) Recovery of neocortical choline acetyltransferase activity following ibotenic acid injection into the nucleus basalis of Meynert in rats. Br. Res. 293: 184–186.Google Scholar
  29. 29.
    Hohman, C. F., Wenk, G. L., Lowenstein, P., Brown, M. E., and Coyle, J. T. (1987) Age-related recurrence of basal forebrain lesion-induced cholinergic deficits. Neurosci Letters 82: 254–259.CrossRefGoogle Scholar
  30. 30.
    Arendash, G. W. Millard, W. J., Dunn, A. and Meyer, E. M. (1987) Longterm neuropathological and neurochemical effects of nucleus basalis lesions in the rat. Science 238: 952–956.Google Scholar
  31. 31.
    Bartus,R. T., Pontecorvo, M. J., Flicker, C., Dean, R. L. and Figueiredo, J. C. (1986) Behavioral recovery following bilateral lesions of the nucleus basalis does not occur spontaneously. Pharm. Blocher Reh. 24: 1287–1292.Google Scholar
  32. 32.
    Amaral, D. G. and Price, J. L. (1983) An air pressure system for the injection of tracer substances into the brain. J. Neurosci. MethodsGoogle Scholar
  33. 33.
    May, A. M. and Arneric, S. P. (1987) Effects of basal forebrain lesions and cholinomimetics on cerebral cortical microvascular perfusion (CCMP) in rat: continuous measurement by laser-doppler flowmetry. Neurosci. Abat. 13: 1034.Google Scholar
  34. 34.
    Hadhazy, P. and Szerb, J. C. (1977) The effect of cholinergic drugs on [3H]-acetylcholine release from slices of rat hippocampus, striatum, and cortex. Br. Res. 123: 311–322. 35. Bradford, M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye-binding. Anal. Biochem. 72: 248–254.Google Scholar
  35. 36.
    Fonnum, F. (1969) Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities. Biochem. J. 115: 465–472.Google Scholar
  36. 37.
    Arneric, S. P., Honig, M. A., Milner, T. A., Greco, S., Iadecola, C. and Reis, D. J. (1988) Neuronal and endothelial sites of acetylcholine synthesis and release associated with microvessels in rat cerebral cortex: ultrastructural and neurochemical studies. Br. Res,. 454: 11–30.Google Scholar
  37. 38.
    El-Defrawy, S. R., Coloma, F., Jhamandas, K., Boegman, R. J., Beninger, R. J. and Wisching, B. A. (1985) Functional and neurochemical cortical cholinergic impairment following neurotoxic lesion of the nucleus basalis magnocellularis in the rat. Neurobio. of Aging 6: 325–330.CrossRefGoogle Scholar
  38. 39.
    Casamenti, F., DiPatre, P. L., Bartolini, L., and Pepeu, G. (1988) Unilateral and bilateral nucleus basalis lesions: differences in neurochemical and behavioral recovery. Neuroscience 24: 209–215.CrossRefGoogle Scholar
  39. 40.
    Pearson, R. C. A., Sofropiew, M. V., and Powell, T. P. S. (1987) The cholinergic nuclei of the basal forebrain of the rat: hypertrophy following contralateral cortical damage or section of the corpus callosum. Br. Res. 411: 332–340.Google Scholar
  40. 41.
    Eckenstein, F. P., Baughman, R. W. and Quinn, J. (1988) An anatomical study of cholinergic innervation in rat cerebral cortex. Neuroscience 25: 457–474.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Martha Downen
    • 1
  • Kimi Sugaya
    • 1
  • Stephen P. Arneric
    • 1
  • Ezio Giacobini
    • 1
  1. 1.Dept. of PharmacologySouthern Illinois University School of MedicineSpringfieldUSA

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