Skip to main content
Log in

Cholinergic Neurotransmission and Synaptic Plasticity Concerning Memory Processing

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The brain is able to change the synaptic strength in response to stimuli that leave a memory trace. Long-term potentiation (LTP) and long-term depression (LTD) are forms of activity-dependent synaptic plasticity proposed to underlie memory. The induction of LTP appears mediated by glutamate acting on AMPA and then on NMDA receptors. Cholinergic muscarinic agonists facilitate learning and memory. Acetylcholine depolarizes pyramidal neurons, reduces inhibition, upregulates NMDA channels and activates the phosphoinositide cascade. Postsynaptic Ca2+ rises and stimulates Ca-dependent PK, promoting synaptic changes. Electroencephalographic desynchronization and hippocampal theta rhythm are related to learning and memory, are inducible by Cholinergic agonists and elicited by hippocampal Cholinergic terminals. Their loss results in memory deficits. Hence, Cholinergic pathways may act synergically with glutamatergic transmission, regulating and leading to synaptic plasticity. The stimulation that induces plasticity in vivo has not been established. The patterns for LTP/LTD induction in vitro may be due to the loss of ascending Cholinergic inputs. As a rat explores pyramidal cells fire bursts that could be relevant to plasticity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Kandel, E. R., and O'Dell, T. J. 1992. Are adult learning mechanisms also used for development? Science 258:243–245.

    Google Scholar 

  2. Bliss, T. V. P., and Lømo, T. 1973. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. (Lond.) 232:331–356.

    Google Scholar 

  3. Bliss, T. V. P., and Collingridge, G. L. 1993. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39.

    Google Scholar 

  4. Dudek, S. M., and Bear, M. F. 1992. Homosynaptic long-term depression in area CA1 of hippocampus and the effects of NMDA receptor blockade. Proc. Natl. Acad. Sci. USA 89:4363–4367.

    Google Scholar 

  5. Mulkey, R. M., and Malenka, R. 1992. Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus. Neuron 9:967–975.

    Google Scholar 

  6. Malenka, R. C., and Nicoll, R. A. 1993. NMDA-receptor-dependent synaptic plasticity: Multiple forms and mechanisms. Trends Neurosci. 16:521–527.

    Google Scholar 

  7. Ben-Ari, Y., Aniksztejn, L., and Bregestovski, P. 1992. Protein kinase C modulation of NMDA currents: an important link for LTP induction. Trends Neurosci. 15:333–339.

    Google Scholar 

  8. Hebb, D. O. 1949. The Organization of Behavior. John Wiley and Sons, Inc., New York.

    Google Scholar 

  9. Nicoll, R. A., and Malenka, R. C. 1995. Contrasting properties of two forms of long-term potentiation in the hippocampus. Nature 377:115–118.

    Google Scholar 

  10. Williams, J. H., Errington, M. L., Lynch, M., and Bliss, T. V. P. 1989. Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus. Nature 341:739–742.

    Google Scholar 

  11. O'Dell, T. J., Kandel, E. R., and Grant, S. G. 1991. Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors. Nature 353:558–560.

    Google Scholar 

  12. Stevens, C. F., and Hwang, Y. 1993. Reversal of long-term potentiation by inhibitors of haeme oxygenase. Nature 364:147–149.

    Google Scholar 

  13. Kato, K., Clark, G. D., Bazán, N. G., and Zorumski, C. F. 1994. Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation. Nature 367:1875–179.

    Google Scholar 

  14. Medina, J. H., and Izquierdo, I. 1995. Retrograde messengers, long term potentiation and memory. Brain Res. Rev., 21:185–194.

    Google Scholar 

  15. Stevens, C. F., and Wang, Y. 1994. Changes in reliability of synaptic function as a mechanism for plasticity. Nature 371:701–706.

    Google Scholar 

  16. Squire, L. R. 1987. Memory and Brain. Oxford University Press, Oxford.

    Google Scholar 

  17. Desimone, R. 1992. The physiology of memory: recordings of things past. Science 258:245–246.

    Google Scholar 

  18. Milner, B. 1985. Memory and the human brain. In Shaffo, M. (ed.), How We Know?, Harper and Row, San Francisco.

    Google Scholar 

  19. Vnek, N., and Rothblat, L. A. 1996. The hippocampus and long-term object memory in the rat. J. Neurosci. 16:2780–2787.

    Google Scholar 

  20. Zola-Morgan, S., Squire, L. R., Clower, R. P., and Rempel, N. L. 1993. Damage to the perirhinal cortex exacerbates memory impairment following lesions to the hippocampal formation. J. Neurosci. 13:251–265.

    Google Scholar 

  21. Klingberg, T., Roland, P. E., and Kawashima, R. 1994. The human entorhinal cortex participates in associative memory. NeuroReport 6:57–60.

    Google Scholar 

  22. Jerusalinsky, D., Ferreira, M. B. C., Walz, R., Da Silva, R. C., Bianchin, M., Ruschel, A., Medina, J. H., and Izquierdo, I. 1992. Amnesia by post-training infusion of glutamate receptor blockers into the amygdala, hippocampus and entorhinal cortex. Behav. Neural Biol. 58:76–80.

    Google Scholar 

  23. Ferreira, M. B. C., Wolfman, C., Walz, R., Da Silva, R. C., Zanatta, M. S., Medina, J. H., and Izquierdo, I. 1992. NMDA-receptor-dependent, muscimol-sensitive role of the entorhinal cortex in post-training memory processing. Behav. Pharmacol. 3:387–391.

    Google Scholar 

  24. Ferreira, M. B. C., Da Silva, R. C., Medina, J. H., and Izquierdo, I. 1992. Late post-training role of the entorhinal cortex in memory processing. Pharmacol. Biochem. Behav. 41:767–771.

    Google Scholar 

  25. Eccles, J. C., Katz, B., and Koketsu, K. 1953. Cholinergic and inhibitory synapses in a central pathway. Austr. J. Sci. 16:50–54.

    Google Scholar 

  26. Karczmar, A. G. 1967. Multiple mechanisms of action of drugs at the neuromyal junction as studied in the light of the phenomenon of “reversal”. Laval Medical 38:465–480.

    Google Scholar 

  27. Drachman, D. S. 1978. Central cholinergic system and memory. Pages 651–652, in Lipton, M. A., and Killian, K. F. (eds.), Psychopharmacology; A Generation of Progress, Raven Press, New York.

    Google Scholar 

  28. Karczmar, A. 1995. Cholinergic substrates of cognition and organism-environment interaction. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 19:187–211.

    Google Scholar 

  29. Izquierdo, I. 1989. Mechanism of the amnestic action of scopolamine. Trends Pharmacol. Sci. 10:175–177.

    Google Scholar 

  30. Izquierdo, I., Medina, J. H., Jerusalinsky, D., and Da Cunha, C. 1992. Post-training memory processing in amygdala, septum and hippocampus: role of benzodiazepine/GABAA receptors, and their interaction with other neurotransmitter systems. Revs. Neurosci. 3:1–13.

    Google Scholar 

  31. Izquierdo, I. 1989. Different forms of post-training memory processing. Behav. Neural Biol., 51:171–202.

    Google Scholar 

  32. Alvarez, P., and Squire, L. R. 1994. Memory consolidation and the medial temporal lobe: A simple network model. Proc. Natl. Acad. Sci. USA 91:7041–7045.

    Google Scholar 

  33. Longo, V. G., and Loizzo, A. 1973. Effects of drugs on hippocampal θ-rhythm. Possible relationships to learning and memory processes. Pages 45–54, in Bloom, F. E., and Acheson, G. H. (eds.), Brain, Nerves and Synapses, Karger, Basel.

    Google Scholar 

  34. Karczmar, A. G. 1979. Brain acetylcholine and animal electrophysiology. Pages 265–310, in Davis, K. L., and Berger, P. A. (eds.), Brain, Acetylcholine and Neuropsychiatric Disease, Plenum Press, New York.

    Google Scholar 

  35. Karczmar, A. G. 1988. Schizophrenia and cholinergic system. Pages 29–63, in Sen, A. G., and Lee, T. (eds.), Receptor and Ligands in Psychiatry, Cambridge University Press, Cambridge.

    Google Scholar 

  36. McCormick, D. A. 1993. Actions of acetylcholine in the cerebral cortex and thalamus and implications for function. Pages 303–308, in Cuello, A. C. (ed.), Cholinergic Function and Dysfunction, Elsevier, Amsterdam.

    Google Scholar 

  37. Karczmar, A. G., Nishi, S., and Blaber, L. C. 1972. Synaptic modulations. Pages 63–92, in Karczmar, A. G., and Eccles, J. C. (eds.), Brain and Human Behavior, Springer-Verlag, Berlin.

    Google Scholar 

  38. Greengard, P. 1976. Possible role for cyclic nucleotides and phosphorylated membrane proteins in postsynaptic actions of neurotransmitters. Nature 260:101–108.

    Google Scholar 

  39. Greengard, P. 1987. Neuronal phosphorproteins. Mol. Neurobiol. 1:81–119.

    Google Scholar 

  40. Hokin, L. E., and Dixon, J. F. 1993. I. Historical background. II. Effects of lithium on the accumulation of second messenger inositol 1, 4, 5-triphosphate in brain cortex slices. Pages 309–315, in Cuello, A. C. (ed.), Cholinergic Function and Dysfunction, Elsevier, Amsterdam.

    Google Scholar 

  41. Maeda, T., Kaneko, S., and Satoh, M. 1993. Bidirectional modulation of long-term potentiation by carbachol via M1 and M2 muscarinic receptors in guinea pig hippocampal mossy fiber-CA3 synapses. Brain Res. 619:324–330.

    Google Scholar 

  42. Marchi, M., and Raiteri, M. 1989. Interaction acetylcholine-glutamate in rat hippocampus: Involvement of two subtypes of M2 muscarinic receptor. J. Pharmacol. Exp. Ther. 248:1255–1260.

    Google Scholar 

  43. Dutar, P., and Nicoll, R. A. 1988. Classification of muscarinic responses in hippocampus in terms of receptor subtypes and second-messenger systems: Electrophysiological studies in vitro. J. Neurosci. 8:4214–4224.

    Google Scholar 

  44. Johnston, D., Williams, S., Jaffe, D., and Gray, R. 1992. NMDA-receptor-independent long-term potentiation. Ann. Rev. Physiol. 54:489–505.

    Google Scholar 

  45. Huerta, P. T., and Lisman, J. E. 1995. Bidirectional synaptic plasticity induced by single burst during cholinergic theta oscillation in CA1 in vitro. Neuron 15:1053–1063.

    Google Scholar 

  46. Izquierdo, I. 1991. Role of NMDA receptor in memory. Trends Pharmacol. Sci. 12:128–129.

    Google Scholar 

  47. Izquierdo, I., Da Cunha, C., Rosat, R., Jerusalinsky, D., Ferreira, M. B. C., and Medina, J. H. 1992. Neurotransmitter receptors involved in memory processing by the amygdala, medial septum and hippocampus of rats. Behav. Neural. Biol. 58:16–26.

    Google Scholar 

  48. Segal, M. 1982. Multiple actions of acetylcholine at a muscarinic receptor studied in the rat hippocampal slice. Brain Res. 246:77–87.

    Google Scholar 

  49. Markram, H., and Segal, M. 1990. Long-lasting facilitation of excitatory postsynaptic potentials in the rat hippocampus by acetylcholine. J. Physiol. 427:381–393.

    Google Scholar 

  50. Markram, H., and Segal, M. 1992. The inositol 1, 4, 5-trisphosphate pathway mediates cholinergic potentiation of rat hippocampal neuronal responses to NMDA. J. Physiol. 447:513–533.

    Google Scholar 

  51. Lin, Y., and Phillis, J. W. 1991. Muscarinic agonist-mediated induction of long-term potentiation in rat cerebral cortex. Brain Res. 551:342–347.

    Google Scholar 

  52. Nicoll, R. A., Malenka, R. C., and Kauer, J. A. 1990. Functional comparison of the neurotransmitter receptor subtypes in mammalian central nervous system. Physiol. Rev. 70:513–565.

    Google Scholar 

  53. Krnjevic, K., Reiffenstein, R. J., and Ropert, N. 1981. Desinhibitory action of acetylcholine in rats' hippocampus: Extracellular observations. Neuroscience 12:2465–2474.

    Google Scholar 

  54. Pitler, T., and Alger, B. E. 1992. Cholinergic excitation of GABAergic interneurons in the rat hippocampal slice. J. Physiol. 450:127–142.

    Google Scholar 

  55. Muller, D., Arai, A., and Lynch, G. S. 1992. Factors governing the potentiation of NMDA receptor-mediated responses in hippocampus. Hippocampus 2:29–38.

    Google Scholar 

  56. Bland, B. H. 1986. The physiology and pharmacology of hippocampal formation theta rhythms. Prog. Neurobiol. 26:1–54.

    Google Scholar 

  57. Winson, J. 1978. Loss of hippocampal theta rhythm result in spatial memory deficit in rat. Science 201:160–163.

    Google Scholar 

  58. Stewart, M., and Fox, S. E. 1990. Do septal neurons pace the hippocampal theta rhythm? Trends Neurosci. 13:163–168.

    Google Scholar 

  59. Huerta, P. T., and Lisman, J. E. 1993. Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364:723–725.

    Google Scholar 

  60. Buszáki, G. 1989. Two-stage model of memory trace formation: A role for “noisy” brain states. Neuroscience 31:551–570.

    Google Scholar 

  61. Steward, M., Luo, Y., and Fox, S. E. 1992. Effects of atropine on hippocampal theta cells and complex-spike cells. Brain Res. 591:122–128.

    Google Scholar 

  62. Burgard, E. C., and Sarvey, J. M. 1990. Muscarinic receptor activation facilitates the induction of long-term potentiation (LTP) in the rat dentate gyrus. Neurosci. Lett. 116:34–39.

    Google Scholar 

  63. Bland, B. H., and Colom, L. V. 1993. Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex. Prog. Neurobiol. 41:157–208.

    Google Scholar 

  64. Buszáki, G., Leung, L. S., and Vanderwolf, C. H. 1983. Cellular basis of hippocampal EEG in the behaving rat. Brain Res. 6:139–171.

    Google Scholar 

  65. O'Keefe, J., and Recce, M. L. 1993. Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3:317–330.

    Google Scholar 

  66. Agmon, A., and Connors, B. W. 1992. Correlation between intrinsic firing patterns and thalamocortical synaptic responses of neurons in mouse barrel cortex. J. Neurosci. 12:319–329.

    Google Scholar 

  67. Hessler, N. A., Shirke, A. M., and Malinow, R. 1993. The probability of transmitter release at a mammalian central synapse. Nature 366:569–572.

    Google Scholar 

  68. Markram, H., and Sakmann, B. 1994. Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc. Natl. Acad. Sci. USA 91:5207–5211.

    Google Scholar 

  69. Nilsson, O. G., Leanza, G., and Björklund, A. 1992. Acetylcholine release in the hippocampus: Regulation by monoaminergic afferents as assessed by in vivo microdialysis. Brain Res. 584:132–140.

    Google Scholar 

  70. Day, J., and Fibiger, H. C. 1993. Dopaminergic regulation of cortical acetylcholine release: effects of dopamine receptor agonists. Neuroscience 54:643–648.

    Google Scholar 

  71. Hersi, A. I., Richard, J. W., Gaudreau, P., and Quirion, R. 1995. Local modulation of hippocampal acetylcholine release by dopamine D1 receptors: a combined receptor autoradiography and in vivo dialysis study. J. Neurosci. 15:7150–7157.

    Google Scholar 

  72. Huang, Y. Y., and Kandel, E. R., 1995. D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. Proc. Natl. Acad. Sci. USA 92:2446–2450.

    Google Scholar 

  73. Smialowski, A. 1985. The effects of intrahippocampal administration of dopamine or apomorphine on EEG of the limbic structure of the rabbit brain. Pol. J. Pharmacol. Pharm. 28:579–586.

    Google Scholar 

  74. Hersi, A. I., Rowe, W., Gandreau, P., and Quirion, R. 1995. Dopamine D1 receptor ligands modulate cognitive performance and hippocampal acetylcholine release in memory impaired aged rats. Neuroscience 69:1067–1074.

    Google Scholar 

  75. Rosenmund, C., Clements, J., and Westbrook, G. L. 1993. Nonuniform probability of glutamate release at a hippocampal synapse. Science 262:754–757.

    Google Scholar 

  76. Malinow, R., Blum, K., Otmakhov, N., and Lisman, J. E. 1994. Visualizing hippocampal synaptic function by optical detection of Ca2+ entry through the N-methyl-aspartate channel. Proc. Natl. Acad. Sci. USA 91:8170.

    Google Scholar 

  77. Davies, C., Starkey, S., Pozza, M., and Collingridge, G. L. 1991. GABAB autoreceptors regulate the induction of LTP. Nature 349:609–611.

    Google Scholar 

  78. Cobb, S. R., Buhl, E. H., Halasy, K., Paulsen, O., and Somogyi, P. 1995. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378:75–78.

    Google Scholar 

  79. Van der Zee, E. A., and Luiten, P. G. M. 1994. Cholinergic and GABAergic neurons in the rat medial septum express muscarinic acetylcholine receptors. Brain Res. 652:263–272.

    Google Scholar 

  80. Toth, K., Borhegyi, Z., and Freund, T. F. 1993. Postsynaptic targets of GABAergic hippocampal neuron in the medial septum-diagonal band of Broca complex. J. Neurosci. 13:475–485.

    Google Scholar 

  81. Izquierdo, I., and Medina, J. H. 1991. GABAA receptor modulation of memory: the role of endogenous benzodiazepines. Trends Pharmacol. Sci. 12:260–265.

    Google Scholar 

  82. Izquierdo, I., Da Cunha, C., Huang, Ch., Walz, R., Wolfman, C., and Medina, J. H. 1990. Post-training down-regulation of memory consolidation by a GABAA mechanism in the amygdala modulated by endogenous benzodiazepines. Behav. Neural. Biol. 54:105–109.

    Google Scholar 

  83. Brioni, J. D., Nagahara, A., and McGaugh, J. L. 1989. Involvement of the amygdala GABAergic system in the modulation of memory storage. Brain Res. 47:105–112.

    Google Scholar 

  84. Izquierdo, I., and Medina, J. H. 1995. Correlation between the pharmacology of LTP and the pharmacology of memory. Neurobiol. Learn. Memory 18–32.

  85. Huang, Y-Y., Colley, P. A., and Routtenberg, A. 1990. Postsynaptic then presynaptic PKC activity may be necessary for long-term potentiation. Neuroscience 4:819–827.

    Google Scholar 

  86. Burchuladze, R., Potter, J., and Rose, S. P. R. 1990. Memory formation: The chick depends on membrane-bound protein kinase C. Brain Res. 535:131–138.

    Google Scholar 

  87. Jerusalinsky, D., Quillfeldt, J., Walz, R., Da Silva, R., Medina, J. H., and Izquierdo, I. 1994. Post-training intrahippocampal infusion of protein kinase C inhibitors causes amnesia in rats. Behav. Neural Biol. 61:107–109.

    Google Scholar 

  88. Bernabeu, R., Izquierdo, I., Cammarota, M., Jerusalinsky, D., and Medina, J. H. 1995. Learning-specific time-dependent increase in 3H-phorbol ester 12,13 dibutyrate to protein kinase C in specific region of the rat brain. Brain Res. 685:163–168.

    Google Scholar 

  89. O'Dell, T. J., and Kandel, E. R. 1994. Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases. Learn. Mem. 1:129–139.

    Google Scholar 

  90. Abraham, W. C., and Bear, M. F. 1996. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 19:126–130.

    Google Scholar 

  91. Cohen, A. S., Kerr, D. S., and Abraham, W. C. 1995. Prior priming activation of metabotropic glutamate receptors lowers the threshold for LTP. Soc. Neurosci. Abstr. 21:602, 246.3.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jerusalinsky, D., Kornisiuk, E. & Izquierdo, I. Cholinergic Neurotransmission and Synaptic Plasticity Concerning Memory Processing. Neurochem Res 22, 507–515 (1997). https://doi.org/10.1023/A:1027376230898

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1027376230898

Navigation