The Chemical Coding Via the Cholinergic System: Its Organization and Behavioral Implications

  • A. G. Karczmar
Part of the Advances in Behavioral Biology book series (ABBI, volume 10)


The central cholinergic synapses which constitute the subject of this paper are those at which the transmission between the presynaptic and the postsynaptic neuron — or, more precisely, between the presynaptic nerve terminal and the postsynaptic membrane — is mediated by acetylcholine (ACh); a complication may arise from the fact that at certain, non-cholinergic synapses ACh may play a modulatory, facilitatory rather than transmissive role. In view of the wide occurrence (cf. below) of the cholinergic synapses or modulations, the cholinergic system must participate significantly in brain functions and behavioral processes* In fact, several participants of this Symposium discussed the cholinergic participation in the appetitive and thermal control (R.D. Myers), in conditioning and learning (H. Brust-Carmona), in aggression (D.J. Reis), and in certain phases of sleep (P. Morgane); related aspects of the cholinergic system were described by others (Domino, 1968; Domino et al., 1968; Bovet-Nitti, 1965; Aprison, 1965; Stein, 1968; Karczmar et al., 1972; Karczmar, 1971).


Cholinergic System Paradoxical Sleep Cholinergic Synapse Chemical Code Central Cholinergic System 
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  1. Andersen, P. and Andersson, S.A., 1968,“Physiological Basis of Alpha Rhythm,” Appleton-Century-Crafts, New York.Google Scholar
  2. Anderson, P. and Curtis, D.R., 1964, The excitation of thalamic neuronesby acetylcholine, Acta Physiol. Scand 61: 85–99.CrossRefGoogle Scholar
  3. Aprison, M.H., 1965, Research approaches to problems in mental illness: Brain neurohumor-enzyme systems, and behavior, in “Progress in Brain Research,” (W.A. Hirawich and J.E. Schade eds), pp. 48–80, 16.Google Scholar
  4. Babb, T.L., Babb, M., Mahnke, J.H. and Verzeano, M., 1971, The action of cholinergic agents on the electrical activity of the non-specific nuclei of the thalamus, Int. J. Neurol. 8: 198–210.PubMedGoogle Scholar
  5. Barker, J.L. and Nicoll, R.A., 1973, The pharmacology and ionic dependency of amino acid responses in the frog spinal cord, J. Physiol. 228: 259–277.PubMedGoogle Scholar
  6. Barnes, L., Cann, F., Karczraar, A0G. and Longo, V.G., 1973a, 5-HTP and DOPA responses in 6-OH dopamine and 5,6-dihydrotryptamine treated mice, Fed. Proc. 32: 276.Google Scholar
  7. Barnes, L., Cann, F., Karczmar, A.G., Kindel, G. and Longo, V.G., 1973b, Effects of L-DOPA on behavior and on brain amines in mice trated with 6-hydroxydopamine, Pharmacol, and Behav. 1: 35–40.CrossRefGoogle Scholar
  8. Bovet-Nitti, F., 1965, Action of nicotine on conditioned behavior in naive and pretrained rats. II. Complex forms of acquired behavior, in “Symposium on Tobacco Alkaloids and Related Compounds,” (U.S.V. Euler, ed.), pp. 137–143, Pergamon Press, Oxford.Google Scholar
  9. Burn, J.H., 1966, Introductory remarks. Section V. Adrenergic transmission, Pharmac. Rev. 18: 459–470.Google Scholar
  10. Campbell, G., 1970, Autonomic nervous supply to effector cells, in “Smooth Musele,” (E. Btilbring, A.F. Brading, A.W. Jones and T. Tomita, eds.), pp. 451–495, The Williams and Wilkins Co., Baltimore.Google Scholar
  11. Christ, D.D. and Nishi, S., 1971, Site of adrenalin blockade in the superior cervical ganglion of the rabbit, J. Physiol. 213: 107–117.PubMedGoogle Scholar
  12. Cosgrove, K.A., Scudder, C.L. and Karczmar, A.G., 1973, Some aspects of acute quantitative shock on mouse whole brain levels of acetylcholine and choline, The Pharmacologist, 15: 255.Google Scholar
  13. Curtis, D.R. and Crawford, J.M., 1969, Central synaptic transmission microelectrophoretic studies, Ann. Rev. Pharmacol. 9: 209–250.PubMedCrossRefGoogle Scholar
  14. Domino, E.F., 1968, Cholinergic mechanisms and the EEG, EEG Clin. Neurophysiol. 24: 292–293.Google Scholar
  15. Domino, E.F., Yamamoto, K. and Dren, A.T., 1968, Role of cholinergic mechanisms in states of wakefulness and sleep, Brain Res. 28: 113–133.CrossRefGoogle Scholar
  16. Eccles, R.M., 1955, Intracellular potentials recorded from a mammalian sympathetic ganglion, J. Physiol. 130: 572–584.PubMedGoogle Scholar
  17. Eccles, J.C., 1969, Historical Introduction, in “Central Cholinergic Transmission and its Behavioral Aspects,” (A.G. Karczmar, ed.), pp. 90–94, Fed. Proc. 28.Google Scholar
  18. Eccles, J.C., 1969, “The Inhibitory Pathways of the Central Nervous System,” Charles C. Thomas (Publ.), Springfield, Illinois.Google Scholar
  19. Eccles, J.C., Fatt, P. and Koketsu, K., 1954, Cholinergic and inhibitory synapses in a pathway from motor axon collaterals to motoneurons, J. Physiol. (Lond.), 216: 524–562.Google Scholar
  20. Eccles, J.C., Schmidt, R.F. and Willis, W.D., 1963, Pharmacological studies of synaptic inhibition, J. Physiol. 168: 500–530.PubMedGoogle Scholar
  21. Essman, W.B., 1972, Neurochemical changes in ECS and ECT, Seminars in Psychiat. 4: 67–79.Google Scholar
  22. Gastaut, H. and Fischer-Williams, M., 1959, The physiopathology of epileptic seizures, in “Handbook of Physiology, Section I: Neurophysiology,” (J. Field, ed.), pp. 329–363, American Physiol, Soc., Washington, D.C.Google Scholar
  23. George, R., Haslett, W.L. and Jenden, D.J., 1964, A cholinergic mechanism in the brain stem reticular formation: induction of paradoxical sleep, Internatl. J. NeuroPharmacol. 3: 541–552.Google Scholar
  24. Glisson, S.N. and Karczmar, A.G., 1971, Atropine methyl nitrate block of diisopropyl fluorophosphate effect on dopamine in rabbit brain, Fed. Proc. 30: 382.Google Scholar
  25. Glisson, S.N., Karczmar, A.G. and Barnes, L., 1972, Cholinergic effects on adrenergic transmitters in rabbit brain parts, Neuropharma col. 11: 465–477.CrossRefGoogle Scholar
  26. Hanigan, W. and Scudder, C.L., 1973, A systems view of seizure patterning, Gen. Syst. Bull. 4: 3–13.Google Scholar
  27. Hanin, I., Massarelli, R. and Costa, E., 1972, An approach to the study of the biochemical pharmacology of cholinergic function, in “Studies of Neurotransmitters at the Synaptic Level,” E. Costa, L.L. Iversen and R. Paoletti, eds.), pp. 181–202, Adv. Biochem. Psychopharmacol. 6.Google Scholar
  28. Hernandez-Peon, R., 1965, Central neurohumoral transmission in sleep and wakefulness, in “Progress in Brain Research, Sleep Mechanisms,” ( K. Akert, C. Bally and J.P. Schade, eds.), pp. 96–116, Elsevier, Amsterdam.CrossRefGoogle Scholar
  29. Hernandez-Peon, R. and Chavez Ibarra, G., 1963, Sleep induced by electrical or chemical stimulation of the forebrain, Electroenceph. Clin. Neurophysiol. Suppl. 24: 188–198.Google Scholar
  30. Himwich, H.E., 1962, Reticular activating system — current concepts of function, Chapter 28, in “Psychosomatic Medicine,” (J.H. Nodine and J.H. Meyer, eds.),pp. 211–220, Lea and Fabiger, Philadelphia.Google Scholar
  31. Hubbard, J.H. and Rayport, M., 1968, Cholinergic induction of thalamo-cortical seizures in cats, EEG Clin. Neurophysiol. 24: 189.Google Scholar
  32. Iwata, N., Sakai, Y. and Deguchi, T., 1971, Effects of physostigmine on the inhibition of trigeminal motoneurons by cutaneous impulses in the cat, Exp. Brain Res. 13: 519–522.PubMedCrossRefGoogle Scholar
  33. Jouvet, M., 1972, Some monoaminergic mechanisms controlling sleep and waking, in “Brain and Human Behavior,” (A.G. Karczmar and J.C. Eccles, eds.), pp. 131–160, Springer-Verlag, Berlin.CrossRefGoogle Scholar
  34. Kaplan, R.L. and Scudder, C.L., 1973, The effect of unavoidable footshock stress on-γ-aminobutyric acid levels in mouse brain, The Pharmacologist. 15: 259.Google Scholar
  35. Karczmar, A.G., 1967, Pharmacologic, toxicologic and therapeutic properties of anticholinesterase agents, in “Physiological Pharmacology,” (W.S. Root and F.G. Hofman, eds.), pp. 163–322, Vol. 3, Academic Press, New York.Google Scholar
  36. Karczmar, A.G., 1969, Is the central cholinergic system overexploited? in “Central Cholinergic Transmission and its Behavioral Aspects,” (A.G. Karczmar, ed.), Fed. Proc. 28: 47–157.Google Scholar
  37. Karczmar, A.G., 1970, Central cholinergic pathways and their be-havioral implications, in “Principles of Psychopharmacology,” (W.G. Clark and J. del Giudice, eds.), pp. 57–86, Academic Press, New York.Google Scholar
  38. Karczmar, A.G., 1971, Possible mechanisms underlying the so-called “Divorce” phenomena of EEG desynchronizing actions of anti-cholinesterases, Presented at the Regional Midwest EEG Meetings, April 1971, Hines V.A. Hospital.Google Scholar
  39. Karczmar, A.G., 1971, Neurophysiologies1 behavioral and neurochemical correlates of the central cholinergic synapses, in “Advances in Neuropsychopharmacology,” ( O. Vinar, Z. Votava and P.B. Bradley, eds.), pp. 455–480, North-Holland Pubi. Co., Amsterdam.Google Scholar
  40. Karczmar, A.G., 1973, Brain acetylcholine and seizures, in “Psychobiology of Electroconvulsive Therapy,” (M. Fink, ed.), Winston and Sons, Publ., New York (in Press).Google Scholar
  41. Karczmar, A.G. and Koppanyi, T., 1953, Central effects of diisopropyl fluorophosphonate in urodele larvae, Schmiedebergs Arch. J. expt. Path. 219: 261–270.Google Scholar
  42. Karczmar, A.G. and Nishi, S., 1971, The types and sites of cholinergic receptors: in “Advances in Cytopharmacology,” (F. Clementi and B. Ceccarelli, eds.), 1: 301–318, Raven Press, New York.Google Scholar
  43. Karczmar, A.G., Longo, V.G. and Scotti de Carolis, A., 1970, A pharmacological model of paradoxical sleep: the role of cholinergic and monoamine systems, Physiology and Behavior 5: 175–182.PubMedCrossRefGoogle Scholar
  44. Karczmar, A.G., Nishi, S. and Blaber, L.C., 1970, Investigations, particularly by means of the anticholinesterase agents, of the multiple peripheral and central cholinergic mechanisms and of their behavioral implications, Acta Vitaminologica et Enzymologica 24: 131–189.PubMedGoogle Scholar
  45. Karczmar, A.G., Nishi, S. and Blaber, L.C., 1972, Synaptic modulations, in “Brain and Humpn Behavior,” (A.G. Karczmar and J.C. Eccles, eds.), pp. 63–92, Springer-Verlag, BerlinCrossRefGoogle Scholar
  46. Karczmar, AG., Scudder, C.L. and Richardson, D., 1973, Interdisciplinary approach to the study of behavior in related mice types, in “Neurosciences Research,” (I. Kopin, ed.), 5: 159–244, Academic Press, New York,Google Scholar
  47. Kidokoro, Y., Kubota, K., Shuto, S. and Sumino, R., 1968, Possible interneurons responsible for reflex inhibition of motoneurons of jaw-closing muscles from inferior dental nerve, J. Neurophysiol, 31: 709–716oPubMedGoogle Scholar
  48. Kiraly, M.K. and Phillis, J.W., 1961, Action of some drugs on the dorsal root potentials of the isolated toad spinal cord, Brit. J. Pharmacol. 17: 224–231.PubMedGoogle Scholar
  49. Koelle, G.B., 1963, Cytological distribution and physiological functions of cholinesterases, in “Cholinesterases and Anticholinesterase Agents, ”(GOB. Koelle, ed.), Handbch. d. Exper. Pharmakol., Ergzungswk., 15: 187–298, Springer-Verlag, Berlin.Google Scholar
  50. Koelle, G.B., 1969, Significance of acetylcholinesterase in central synaptic transmission, in “Symposium on Central Cholinergic Transmission and its Behavioral Aspects,” (A.G. Karczmar, ed.), Fed. Proc., 28: 147–157.Google Scholar
  51. Koelle, G.B., 1969b, Pharmacology of synaptic transmission, in “Basic Mechanisms of the Epilepsies,” (H.H. Jasper, A.A. Ward, Jr., and A. Pope, eds. ), pp. 195–211.Google Scholar
  52. Koketsu, K., 1969, Cholinergic synaptic potentials and the underlying ionic mechanisms, In “Central Cholinergic Transmission and its Behavioral Aspects,” (A.G. Karczmar, ed.), Fed. Proc., 28: 101–112.Google Scholar
  53. Koketsu, K., Karczmar, A.G. and Kitamura, R., 1969, Acetylcholine depolarization of the dorsal root nerve terminals in the amphibian spinal cord, Int. J. Neuro-Pharmacol., 8: 329–336.Google Scholar
  54. Kottegoda, S.R., 1970, Peristalsis of the small intestine, in “Smooth Muscle,” (E. Mibring, A.F. Brading, A.W. Jones and T. Tomita, eds.), pp. 525–541, The Williams and Wilkins Co., Baltimore.Google Scholar
  55. Krnjevic, K., 1969, Central cholinergic pathways, in “Central Cholinergic Transmission and its Behavioral Aspects,” (A.G. Karczmar, ed.), Fed. Proc., 28: 113–120.Google Scholar
  56. Krnjevic, K., 1970, Dopamine, acetylcholine and excitatory amino acids in nigrostriatal transmission, in “L-DOPA and Parkinsonism,” (A. Barbeau and F.H. McDowell, eds.), pp. 189–190, F.A. Davis Co., Philadelphia.Google Scholar
  57. Krnjevic K. and Schwartz, S., 1967, The action of i-aminobutyric acid on cortical neurones, Exptl. Brain Res. 3: 320–336.CrossRefGoogle Scholar
  58. Krnjevic, K., Purnain, R. and Renaud, L., 1971, The mechanism of excitation by acetylcholine in the cerebral cortex, J. Physiol. 215: 247–268.PubMedGoogle Scholar
  59. Lewis, P.R. and Shute, C.C.D., 1966, The distribution of cholinesterase in cholinergic neurons demonstrated with electrone microscope, J. Cell Science, 1: 381–390.PubMedGoogle Scholar
  60. Libet, B. and Kobayashi, H., 1969, Generation of adrenergic and cholinergic potentials in sympathetic ganglion cells, Science, 164: 1530–1532.PubMedCrossRefGoogle Scholar
  61. Lomax, P., 1969, Drugs and body temperature, Int. Rev. Neurobiol. 12: 1–43.CrossRefGoogle Scholar
  62. Lomax, P., Foster, R.S. and Kirkpatrick, W.E.,1969, Cholinergic and adrenergic interaction in the flermoregulatory centers of the rat, Brain Res, 15: 431–438.Google Scholar
  63. Longo, V.G., 1962, Electroencephalographic atlas for pharmacological research, Elsevier Publ. Co., Amsterdam.Google Scholar
  64. Longo, V.G. and Silvestrini, G., 1957, Action of eserine and amphetamine on the electrical activity of rabbit brain, J. Pharmacol. Exptl. Therap. 120: 160–170.Google Scholar
  65. Machne, X. and Unna, K.R.W., 1963, Actions of the central nervous system, in “Cholinesterases and Anticholinesterase Agents,” (G.B. Koelle, ed.), Hndbch, d. exper. Pharmakol. Erganzungswk., 15: 679–700, Springer-Verlag, Berlin.Google Scholar
  66. Marczynski, T.J., 1967, Topical application of drugs to subcortical brain structures and related aspects of electrical stimulation Ergebn. d. Physiol. Biol, Chem. Exp, Pharmakol, 59: 86–159.Google Scholar
  67. Martin, W,R. and Eades, C.G,, 1967, Pharmacological studies of spinal cord adrenergic and cholinergic mechanisms and their relation to physical dependence on morphine, Psychopharmacologia 11: 195–223,PubMedCrossRefGoogle Scholar
  68. Morrell, F., 1967, Electrical signs of sensory coding, in “The Neurosciences,” (JVC, Quarton, T, Melnechuk and F.O. Schmitt, eds.), pp. 452–468, The Rockefeller Press, New York.Google Scholar
  69. Nishi, S., 1970, Cholinergic and adrenergic receptors at sympathetic preganglionic nerve terminals, Fed. Proc. 29: 1457–1465,Google Scholar
  70. Nishi, S., Minota, S, and Karczmar, A.G., 1973b, The GABA-mediated depolarization of Primary afferent neurons, The Physiologist, (in Press).Google Scholar
  71. Nishi, S., Minota, S. and Karczmar, A.G., 1973c, Primary afferent neurons: The ionic mechanism of GABA-mediate depolarization, Science (in Press).Google Scholar
  72. Phillis, J.W., 1971, The pharmacology of thalamic and geniculate neurons, Int. Rev. Neurobiol. 14: 1–48.PubMedCrossRefGoogle Scholar
  73. Pradhan, S.N. and Dutta, S.N., 1971, Central cholinergic mechanism and behavior, Int. Rev. Neurobiol. 14: 173–231.PubMedCrossRefGoogle Scholar
  74. Reid, W., Haubrich, D. and Krishna, G., 1971, Enzymatic radioassay for estimating brain levels of acetylcholine and choline, Anal, Biochem. 42: 392–396.CrossRefGoogle Scholar
  75. Richardson, D., Karczmar, A.G., and C,L. Scudder, 1972, Behavioral neurochemical correlates of stress, Proc. Fifth Int, Cong. Pharmacol., p. 192.Google Scholar
  76. Rinaldi, F. and Himwich, H., 1955, Cholinergic mechanisms involved in function of mesodiencephalic activating system, Arch. Neurol. Psychiat. 73: 396–402.Google Scholar
  77. Scudder, C.L., 1971, The brain: A neurohumorally regulated ultra-homeostat. Gen. Syst. Bull. 3: 2–11.Google Scholar
  78. Scudder, C.L., Karczmar, A.G., Everett, G.M., Gibson, E. and Rifkin, M., 1966, Brain catechol and serotonin levels in various strains and genera of mice and a possible interpretation for the correlations of amine levels with electroshock latency and behavior, Int. J. Neuropbarmacol., 5: 343–351.CrossRefGoogle Scholar
  79. Sethy, V.H. and Van Woert, M.H., 1973, Effect of L-DOPA on brain acetylcholine and choline in rats, Neuropharmacolo 12: 27–31.CrossRefGoogle Scholar
  80. Stein, L., 1968, Chemistry of reward and punishment, in “Psychopharmacology. A Review of Progress 1957 to 1967,” (D.H. Efron, ed.), pp. 105–124, U.S. Govt, Printing Office, PHS Publ. No. 836, Washington, D.C.Google Scholar
  81. Tebécis, A.K., 1970a, Properties of cholinoceptive neurons in the medial geniculate nucleus, Brit. J. Pharmacol. 38: 117–137.Google Scholar
  82. Tebecis, A.K., 1970b, Studies on cholinergic transmission in the medial geniculate nucleus, Brit. J. Pharmacol. 38: 138–147.Google Scholar
  83. Toman, J., 1963, Some aspects of central nervous pharmacology, Ann. Rev. Pharmacol. 3: 153–184.CrossRefGoogle Scholar
  84. Van Meter, W., 1970, “Responses to anticholinesterases,” Ph.D. Thesis, Loyola University, Chicago, Illinois.Google Scholar
  85. Van Meter, W. and Karczmar, A.G., 1967, Effects of catecholamine depletion on anticholinesterase activity in the central nervous system, Fed. Proc. 26: 651.Google Scholar
  86. Van Meter, W.G. and Karczmar, A.G., 1971, An effect of physostigmine on the central nervous system of rabbits, related to brain levels of norepinephrine, Neuropharmacol. 10: 379–390.CrossRefGoogle Scholar
  87. Varagic, V. and Kristic, M., 1966, Adrenergic activation by anti-cholinesterases, Pharmac. Rev. 18: 796–800.Google Scholar
  88. Vazquez, A.J. and Krip, G., 1973, Evidence for an inhibitory role for acetylcholine, catecholamines, and serotonin on the cerebral cortex, in “Chemical Modulation of Brain Function — A Tribute to J.E.P. Toman,” (U.C. Sabelli, ed.), pp. 137–159, Raven Press, Pubis., New York.Google Scholar
  89. Wikler, A., 1952, Pharmacologic dissociation of behavior and EEG sleep patterns in dogs: Morphine, n-allyl normorphine and atropine, Proc. Soc. Exptl. Biol. Med. 79: 261–265.Google Scholar
  90. York, D.H., 1967, The inhibitory action of dopamine on the neurons of the caudate nucleus, Brain Res. 5: 263–266.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1974

Authors and Affiliations

  • A. G. Karczmar
    • 1
    • 2
  1. 1.Department of PharmacologyLoyola University Medical CenterMaywoodUSA
  2. 2.Institute for Mind, Drugs and BehaviorLoyola University Medical CenterMaywoodUSA

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