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Basal Forebrain Cholinergic System: A Functional Analysis

  • David Olton
  • Alicja Markowska
  • Mary Lou Voytko
  • Ben Givens
  • Linda Gorman
  • Gary Wenk
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 295)

Abstract

Describing the function of the basal forebrain cholinergic system (BFCS) is complicated by the fact that both anatomical and neurochemical criteria define the system. Ideally, functions would be described for only the cholinergic cells in only this brain area. As will be indicated below, for technical reasons, functional analyses of the BFCS have not often achieved this goal. For example, studies examining the behavioral consequences of lesions in the nucleus basalis magnocellularis (NBM) and medial septal area (MSA), two areas of the BFCS, have often used a neurotoxin such as ibotenic (IBO) acid to produce the lesion. Although IBO clearly destroys many cholinergic cells, it is not specific for just the cholinergic system, and destroys noncholinergic cells also. Determining the extent to which the behavioral consequences of these lesions depend upon the destruction of the cholinergic cells, as compared to the noncholinergic cells, is very difficult. Likewise, measures of sodium dependent high affinity choline uptake (HACU) in the frontal cortex (FC), a projection area for cholinergic cells in the NBM, is complicated by the fact the FC has intrinsic cholinergic neurons.

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References

  1. Aigner, T., Mitchell, S., Aggleton, J., et al. (1987). Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert. Psvchopharmacoloav. 92, 292–300.CrossRefGoogle Scholar
  2. Aigner, T. G., Mitchell, S. J., Aggleton, J. P., et al. (1990). Transient impairment of recognition memory following ibotenic-acid lesions of the basal forebrain in macaques. Manuscript Submitted.Google Scholar
  3. Bartus, R. T., Flicker, C., Dean, R. L., Pontecorvo, M., Figueiredo, J. C., & Fisher, S. K. (1985a). Selective memory loss following nucleus basalis lesions: Long term behavioral recovery despite persistent cholinergic deficiencies. Pharmacol. Biochem. Behav., 23, 125–135.PubMedCrossRefGoogle Scholar
  4. Bartus, R.T., Reginald, L.D., Pontecorvo, M.J., & Flicker, C. (1985b). The cholinergic hypothesis: a historical overview, current perspective, and future directions. In D. S. Olton, E. Gamzu, & S. Corkin. (Eds.), Memory dysfunctions; An integration of animal and human research from preclinical and clinical perspectives (pp. 332–358). New York: The New York Academy of Sciences.Google Scholar
  5. Bostock, E., Gallagher, M., & King, R.A. (1988). Effects of opioid microinjections into the medial septal area on spatial memory in rats. Behavioral Neuroscience, 102, 643–652.PubMedCrossRefGoogle Scholar
  6. Coffey, P. J-, Perry, V. H., Allen, Y., Sinden, J., & Rawlins, J. N. P. (1988). Ibotenic acid induced demyelination in the central nervous system: A consequence of a local inflammatory response. Neuroscience Letter, 84, 171–184.CrossRefGoogle Scholar
  7. Davis, H.P., & Volpe, B.T. (In Press). Memory performance after ischemic or neurotoxin damage of the hippocampus. In L. R. Squire, & E. Lindenlaub. (Eds.).The Biology of Memorv. Symposia MedicaHoechst 23 New York: Stuttgart.Google Scholar
  8. Dunnett, S. B., Whishaw, I. Q., Jones, G. H., & Bunch, S. T. (1987). Behavioural, biochemical and histochemical effects of different neurotoxic amino acids injected into nucleus basalis magnocellularis of rats. Neuroscience., 20, 653.PubMedCrossRefGoogle Scholar
  9. Dunnett, S. B. (In Press). Comparison of short-term memory deficits in animal models of ageing using an operant delayed response task in rats. The Biologv of Memory.Google Scholar
  10. Durkin, T. (1989). Central cholinergic pathways and learning and memory processes: presynaptic aspects. Comp. Biochem. Physiol., 93A(1), 273–280.CrossRefGoogle Scholar
  11. Etherington, R., Mittleman, G., & Robbins, T. W. (1987). Comparative effects of nucleus basalis and fimbria-fornix lesions on delayed matching and alternation tests of memory. Neurosci. Res.Communie., 1, 135–143.Google Scholar
  12. Fuster, J.M. (1989). The prefrontal cortex: Anatomy. physiology, and neuropsychology of the frontal lobe (2nd ed.). New York:Raven Press.Google Scholar
  13. Gallagher, M., Meagher, M.W., & E. Bostock. (1987). Effects of opiate manipulations on latent inhibition in rabbits: Sensitivity of the medial septal region to intracranial treatments. Behavioral Neuroscience. 101. 315–324.PubMedCrossRefGoogle Scholar
  14. Gerbec, E. N., Messing, R. B., & Sparber, S. B. (1988). Parallel changes in operant behavioral adaptation and hippocampal corticosterone binding in rats treated with trimethyltin. Brain Research. 460. 346–351.PubMedCrossRefGoogle Scholar
  15. Givens, B. S., & Olton, D. S. (In Press). Modulation of medial septal area alters working memory: GABA and Ach may influence memory through a common mechanism in the medial septal area. Behavioral Neuroscience.Google Scholar
  16. Handelmann, G. E., & Olton, D. S. (1981). Recovery of function after neurotoxic damage to the hippocampal CA3 region: Importance of postoperative recovery interval and task experience. Behav. Neural Biol., 33. 453–464.PubMedCrossRefGoogle Scholar
  17. Kepler, D. J., Olton, D. S., Wenk, G. L., & Coyle, J. T. (1985). Lesions in nucleus basalis magnocellularis and medial septal area of rats produce qualitatively similar memory impairments. The Journal of Neuroscience, 5(4), 866–873.Google Scholar
  18. Irle, E., & Markowitsch, H. J. (1987). Basal forebrain-lesioned monkeys are severely impaired in tasks of association and recognition memory. Annals of Neurology, 22, 735–743.PubMedCrossRefGoogle Scholar
  19. Kesner, R. P., Adelstein, T., & Crutcher, K. A. (1987). Rats with nucleus basalis magnocellularis lesions mimic mnemonic symptomatology observed in patient with dementia of the Alzheimer’s type. Behav. Neurosci., 101(4), 451–456.PubMedCrossRefGoogle Scholar
  20. Kesner, R. P. (1988). Reevaluation of the contribution of the basal forebrain cholinergic system to memory. Neurobiology of Aging, 9, 609–616.PubMedCrossRefGoogle Scholar
  21. Kesner, R. P., Crutcher, K. A., & Beers, D. R. (1989). Serial position curves for item (spatial location) information: Role of the dorsal hippocampal formation and medial septum. Brain Research, 454, 219–226.CrossRefGoogle Scholar
  22. Kolb, B. (1984). Functions of the frontal cortex of the rat: A comparative review. Brain Research Review, 8, 65–98.CrossRefGoogle Scholar
  23. Leranth, C. & Frotscher, M. (1989). Organization of the septal region in the rat: Cholinergic-Gabaergic interconnections and the termination of hippocamposeptal fibers. Journal of Comparative Neurologv, 289, 304–314.CrossRefGoogle Scholar
  24. Majchrzak, M., Brailowsky, S., & Will, B. (1990). Chronic infusion of GABA and saline into the nucleus basalis magnocellularis of rats: II. Cognitive impairments. Behavioral Brain Research, 37, 45–56.CrossRefGoogle Scholar
  25. Markowska, A. L., Olton, D. S., Murray, E. A., & Gaffan, D. (1989). A comparative analysis of the role of the fornix and cingulate cortex in memory: Rats. Experimental Brain Research, 74, 255–269.CrossRefGoogle Scholar
  26. Markowska, A.L., Givens, B., & Olton, D.S. (1990). Cholinergic activation of medial septal area can restore working memory in old rats and in scopolamine-treated young rats. Society for Neuroscience Abstracts.Google Scholar
  27. Markowska, A. L., Wenk, G. L., & Olton, D. S. (In Press). Nucleus basalis magnocellularis and memory: Differential effects of two neurotoxins. Behavioral and Neural Biology.Google Scholar
  28. Meek, W. H., Church, R. M., & Olton, D. S. (1984). Hippocampus, time, and memory. Behavioral Neuroscience, 98, 3–22.CrossRefGoogle Scholar
  29. Meek, W. H., Church, R. M., Wenk, G. L., & Olton, D. S. (1987). Nucleus basalis magnocellularis and medial septal area lesions differentially impair temporal memory. Journal of Neuroscience, 7(11), 3505–3511.Google Scholar
  30. Messing, R. B., & Aanonsen, L. M. (1989). Trimethyltin (TMT) effects on hippocampal phencyclidine receptors: Dose-dependent decreases in CA and increases in dentate. Society for Neuroscience Abstracts, 1351.Google Scholar
  31. Messing, R. B., & Sparber, B. S. (1986). Increased forebrain adrenergic ligand binding induced by trimethlytin. Toxicology Letters, 32: 107–112.Google Scholar
  32. Mitchel, S. J., Rawlins, J. A., Steward, O., & Olton, D. S. (1982). Medial septal area lesions disrupt theta rhythm and cholinergic staining in medial entorhinal cortex, and produce impaired radial arm maze behavior in rats. The Journal of Neuroscience, 2, 292–300.Google Scholar
  33. Mizumori, S.J., McNaughton, B.L., Barnes, C.A. & Fox, K.B. (1989). Preserved spatial coding in hippocampal CAl pyramidal cells during reversible suppression of CA3c output: evidence for pattern completion in the hippocampus. Journal of Neuroscience. 9, 3915–3928.PubMedGoogle Scholar
  34. Nagel, J.A., & Huston, J.P. (1988). Enhanced inhibitory avoidance learning produced by post-trial injections of substance P into the basal forebrain. Behavioral and Neural Biology, 49, 374–385.PubMedCrossRefGoogle Scholar
  35. O’Keefe, J., & Nadel, L. (1978). The Hippocampus as a cognitive map Oxford:Clarendon Press.Google Scholar
  36. Olton, D.S. (1986). Interventional approaches to memory: Lesions. In J. L. Martinez, & R. Kesner. (Eds.), Learning and Memory: A Biological View (pp. 379–397). New York: Academic Press.Google Scholar
  37. Olton, D.S. (1989a). Mnemonic functions of the hippocampus: single unit analyses in rats. In V. Chan-Palay, & C. Kohier. (Eds.). Neurology and neurobiology. The Hippocampus New Vistas (pp. 411–424). New York: Alan R. Liss, Inc.Google Scholar
  38. Olton, D.S. (1989b). Dimensional mnemonics. In G. H. Bower. (Ed.), (pp. 1–23). San Diego: Academic Press.Google Scholar
  39. Olton, D. S., Becker, J. T., & Handelmann, G. E. (1979). Hippocampus, space and memory. The Behavioral and Brain Sciences, 2, 313–322.CrossRefGoogle Scholar
  40. Olton, D.S., & Wenk, G.L. (1987). Dementia:Animal models of the cognitive impairments produced by degeneration of the basal forebrain cholinergic system. In H. Y. Meitzer. (Ed.), Psychopharmacology: The third generation of progress (pp. 941–953). New York: Raven Press.Google Scholar
  41. Olton, D. S., Meek, W. H., & Church, R. M. (1987). Separation of hippocampal and amygdaloid involvement in temporal memory dysfunctions. Brain Research, 404, 180–188.PubMedCrossRefGoogle Scholar
  42. Olton, D. S., Wenk, G. L., Church, R. M., & Meek, W. H. (1988). Attention and the frontal cortex as examined by simultaneous temporal processing. Neuropsychologia, 26(2), 307–318.PubMedCrossRefGoogle Scholar
  43. Olton, D.S., & Markowska, A.L. (1989). The effects of preoperatiave experience upon postoperative performance of rats following lesions of the hippocampal systems. In J. Schulkin. (Ed.) Preoperative events (pp. 151–173). Hillsdale, New Jersey: Lawrence Erlbaum Associates, Publishers.Google Scholar
  44. Olton, D.S., Wenk, G.L., & Markowska, A.M. (In Press). Basal forebrain, memory, and attention. In R. Richardson. (Ed.). Activation to acquisition: Functional aspects of the basal forebrain Boston: Birkhauser.Google Scholar
  45. Powell, D.A., Hernandez, L., & Buchanan, S.L. (1985) Intraseptal scopolamine has differential effects on Pavlovian eye blink and heart rate conditioning. Behavioral Neuroscience, 99, 75–87.PubMedCrossRefGoogle Scholar
  46. Raffaele, K. C., & Olton, D. S. (1988). Hippocampal and amygdaloid involvement in working memory for nonspatial stimuli. Behavioral Neuroscience. 102. 349–355.PubMedCrossRefGoogle Scholar
  47. Ridley, R. M., Baker, H. F., Drewett, B., & Johnson, J. A. (1985). Effects of ibotenic acid lesions of the basal forebrain on serial reversal learning in marmosets. Psvchopharmacoloqy, 60, 438–443.CrossRefGoogle Scholar
  48. Ridley, R. M., Murray, T. K., Johnson, J. A., & Baker, H. F. (1986). Learning impairment following lesion of the basal nucleus of Meynert in the marmoset: Modification by cholinergic drugs. Brain Research, 376, 108–116.PubMedCrossRefGoogle Scholar
  49. Ridley, R. M., Aitken, D. M., & Baker, H. F. (1989). Learning about rules but not about reward is impaired following lesions of the cholinergic projection to the hippocampus. Brain Research, 502, 306–318.PubMedCrossRefGoogle Scholar
  50. Robbins, T. W., Everitt, B. J., Ryan, C. N., Marston, H. M., Jones, G. H., & Page, K. J. (1989). Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and the globus pallidus on the acquisition of a conditional visual discrimination: Differential effects on cholinergic mechanisms. Neurosci., 28, 337–352.CrossRefGoogle Scholar
  51. Robinson, S.E., Hambrecht, K.L. & Lyeth, B.G. (1988). Basal forebrain carbachol injection reduces cortical acetylcholine turnover and disrupts memory. Brain Research, 445, 160–164.PubMedCrossRefGoogle Scholar
  52. Sarter, M., Bruno, J. P., & Dudchenko, P. (1990). Activating the damaged basal forebrain cholinergic system: tonic stimulation versus signal amplification. PsychopharmacoloQV, 101, 1–17.CrossRefGoogle Scholar
  53. Sarter, M., & Dudchenko, P. (In Press). Dissociative effects of ibotenic and quisqualic acid-induced basal forebrain lesions on cortical AChE-positive fiber density and cytochrome oxidase activity. Neuroscience.Google Scholar
  54. Toumane, A., Durkin, T., Marighetto, A., Galey, D., & Jaffard, R. (1988). Differential hippocampal and cortical cholinergic activation during the acquisition, retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze by mice. Behavioral Brain Research, 30, 225–234.CrossRefGoogle Scholar
  55. Toumane, A., Durkin, T., Marighetto, A., & Jaffard, R. (1989). The durations of hippocampal and cortical cholinergic activation induced by spatial discrimination testing of mice in an eight-arm radial maze decrease as a function of acquisition. Behavioral and Neural Biology, 52, 279–284.PubMedCrossRefGoogle Scholar
  56. Volpe, B. T., Davis, H. P., & Colombo, P. J. (1989). Preoperative training modifies radial maze performance in rats with ischemic hippocampal injury. Stroke, 20. 1700–1706.PubMedCrossRefGoogle Scholar
  57. Voytko, M. L., Olton, D. S., Richardson, R. T., Wenk, G. L., & Price, D. L. (1990). Lack of memory impairments following basal forebrain lesions in monkeys. Society of Neuroscience.Google Scholar
  58. Wenk, G. L., & Olton, D. S. (1984). Recovery of neocortical choline acetyltransferase activity following ibotenic acid injection in the nucleus basalis of Meynert in rats. Brain Research, 293, 184–186.PubMedCrossRefGoogle Scholar
  59. Wenk, G., Kepler, D., & Olton, D. (1984). Behavior alters the uptake of [3H]choline into acetylcholinergic neurons of the nucleus basalis magnocellularis and medial septal area. Behavioural Brain Research, 13, 129–138.PubMedCrossRefGoogle Scholar
  60. Wenk, G. L., Cribbs, B., & McCall, L. (1984). Nucleus basalis magnocellularis: Optimal coordinates for selective reduction of choline acetyltransferase in frontal neocortex by ibotenic acid injections. Exp. Brain Res., 56, 335–340.PubMedCrossRefGoogle Scholar
  61. Wenk, G.L., & Olton, D.S. (1987). Basal forebrain cholinergic neurons and Alzheimer’s disease. In J. T. Coyle. (Ed.). Animal models of dementia (pp. 81–101). New York: Alan R. Liss, Inc.Google Scholar
  62. Wenk, G. L., Markowska, A. L., & Olton, D. S. (1989). Basal forebrain lesions and memory: Alterations in neurotensin, not acetylcholine, may cause amnesia. Behav.Neurosei., 103. 765–769.CrossRefGoogle Scholar
  63. Whishaw, I. Q., O’Connor, W. T., & Dunnett, S. B. (1985). Disruption of central cholinergic systems in the rat by basal forebrain lesions or atropine: Effects on feeding, senosrimotor behaviour, locomotor activity and spatial navigation. Behavioural Brain Research, 17, 103–115.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • David Olton
    • 1
  • Alicja Markowska
    • 1
  • Mary Lou Voytko
    • 1
  • Ben Givens
    • 1
  • Linda Gorman
    • 1
  • Gary Wenk
    • 1
  1. 1.Department of PsychologyThe Johns Hopkins UniversityBaltimoreUSA

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