Ascending Cholinergic Control of the Neocortex and Hippocampus

  • C. H. Vanderwolf


In 1967, two British neuroscientists, P.R. Lewis and C.C.D. Shute, published a pair of papers1 on what they called the “ascending cholinergic reticular system”, a system of ascending cholinergic projections from the brainstem to the cerebral cortex. It was known at the time that drugs (anticholinesterases) that inhibit acetylcholinesterase, the enzyme involved in the breakdown of acetylcholine, produce low voltage fast activity in the neocortex and rhythmical slow activity in the hippocampus (neocortical and hippocampal activation). Conversely drugs that block muscarinic cholinergic transmission in the brain block at least one component of neocortical and hippocampal activation (see Chapters 4, 5 and 6). Therefore, it seemed reasonable to think that the actions of anticholinesterases and anti-muscarinic drugs on neocortical and hippocampal activity were due to interference with the normal function of an ascending cholinergic activating system.


Basal Forebrain Slow Wave Activity Septal Nucleus Ibotenic Acid Basal Forebrain Cholinergic Neuron 
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Notes on Chapter 7

  1. Lewis, P.R., and Shute, C.C.D. (1967). The cholinergic limbic system: Projection to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supraoptic crest. Brain, 90: 521-540. 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
  2. 2.
    Davies, P., and Maloney, A.J.F. (1976). Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet, 1403. Whitehouse, P.J., Price, D.L., Clark, A.W., Coyle, J.T., and DeLong, M.R. (1981). Alzheimer’s disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Annals of Neurology, 10: 122 - 126.Google Scholar
  3. 3.
    This effect is reminiscent of the severe depression of slow wave activity (both the irregular waves and the rhythmical waves) in the hippocampus when the septal nuclei are destroyed. The substantia innominata and nucleus basalis of Meynert appear to stand in the same relation to the neocortex as the septal nuclei do to the hippocampus.Google Scholar
  4. 4.
    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 Research, 322: 219 - 232.PubMedCrossRefGoogle Scholar
  5. 5.
    Vanderwolf, C.H., Raithby, A., Snider, M., Cristi, C., and Tanner, C. (1993). Effects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions. Brain Research Bulletin, 31: 515 - 521.PubMedCrossRefGoogle Scholar
  6. 6.
    Vanderwolf, C.H., Fine, A., and Cooley, R.K. (1990). Intracortical grafts of embryonic basal forebrain tissue restore low voltage fast activity in rats with basal forebrain lesions. Experimental Brain Research, 81: 426432.Google Scholar
  7. 7. Gilbert, M.E., and Peterson, G.M. (1991). Colchicine-induced deafferentation of the hippocampus selectively disrupts cholinergic rhythmical slow wave activity. Brain Research, 564: 117-126. Google Scholar
  8. 8.
    Vanderwolf, C.H., Harvey, G.C., and Leung, L.-W.S. (1987). Transcallosal evoked potentials in relation to behavior in the rat: effects of atropine, p-chlorophenylalanine, reserpine, scopolamine, and trifluoperazine. Behavioural Brain Research, 25; 31 - 48.PubMedCrossRefGoogle Scholar
  9. 9.
    Leung, L.-W.S., and Borst, J.G.G. (1987). Electrical activity of the cingulate cortex. I. Generating mechanisms and relations to behavior. Brain Research, 407: 68-80. Borst, J.G.G., Leung, L.-W.S., and MacFabe, D.F. (1987). Electrical activity of the cingulate cortex. II. Cholinergic modulation. Brain Research, 407: 81 - 93.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2003

Authors and Affiliations

  • C. H. Vanderwolf
    • 1
  1. 1.University of Western OntarioLondonCanada

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