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Cellular Studies of an Associative Mechanism for Classical Conditioning in Aplysia

Activity-dependent Presynaptic Facilitation
  • Thomas W. Abrams

Abstract

For much of this century, a central goal for both psychologists and neurobiologists has been to understand the mechanisms underlying associative learning. Of the various forms of associative learning, classical conditioning is perhaps the simplest and is thought to be the prototypical way in which an animal learns a predictive relationship (Pavlov, 1927; Kamin, 1969; Rescorla and Wagner, 1972). In classical conditioning, an animal alters its response to one stimulus as a result of the temporal pairing of this stimulus with a second event. During training, the animal comes to know that the first stimulus, called the conditioned stimulus, signals the occurrence of the second stimulus, the unconditioned stimulus. Because of its simplicity, many of the efforts to analyze cellular mechanisms of associative learning have focused on classical conditioning.

Keywords

Conditioned Stimulus Sensory Neuron Unconditioned Stimulus Classical Conditioning Spike Train 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abrams, T. W., Carew, T. J., Hawkins, R. D., and Kandel, E. R., 1983, Aspects of the cellular mechanism of temporal specificity in conditioning in Aplysia: Preliminary evidence for Ca2+ influx as a signal of activity, Soc. Neurosci. Abstr. 9:168.Google Scholar
  2. Abrams, T. W., Bernier, L., Hawkins, R. D., and Kandel, E. R., 1984a, Possible roles of Ca2+ and cAMP in activity-dependent facilitation, a mechanism for associative learning in Aplysia, Soc. Neurosci. Abstr. 10:269.Google Scholar
  3. Abrams, T. W., Castellucci, V. F., Camardo, J. S., Kandel, E. R., and Lloyd, P. E., 1984b, Two endogenous neuropeptides modulate the gill and siphon withdrawal reflex in Aplysia by presynaptic facilitation involving cAMP-dependent closure of a serotonin-sensitive potassium channel. Proc. Natl. Acad. Sci. USA 81:7956–7960.PubMedCrossRefGoogle Scholar
  4. Alkon, D. L., Lederhendler, I., and Shoukimas, J. L., 1982, Primary changes of membrane currents during retention of associative learning, Science 215:693–695.PubMedCrossRefGoogle Scholar
  5. Bailey, C. H., and Chen, M., 1983, Morphological basis of long-term habituation and sensitization in Aplysia, Science 220:91–93.PubMedCrossRefGoogle Scholar
  6. Bernier, L., Castellucci, V. F., Kandel, E. R., and Schwartz, J. H., 1982, Facilitatory transmitter causes a selective and prolonged increase in adenosine 3′:5′-monophosphate in sensory neurons mediating the gill and siphon withdrawal reflex in Aplysia, J. Neurosci. 2:1682–1691.PubMedGoogle Scholar
  7. Brons, J. F., and Woody, C. D., 1980, Long-term changes in excitability of cortical neurons after Pav-lovian conditioning and extinction, J. Neurophysiol. 44:605–615.PubMedGoogle Scholar
  8. Brostrom, M. A., Brostrom, C. O., Breckenridge, B. McL., and Wolff, D. J., 1978, Calcium-dependent regulation of brain adenylate cyclase, Adv. Cyclic Nucleotide Res. 9:85–99.PubMedGoogle Scholar
  9. Brunelli, M., Castellucci, V., and Kandel, E. R., 1976, Synaptic facilitation and behavioral sensitization in Aplysia: Possible role of serotonin and cyclic AMP, Science 194:1178–1181.PubMedCrossRefGoogle Scholar
  10. Byrne, J. Castellucci, V. F., and Kandel, E. R., 1974, Receptive fields and response properties of mechanoreceptor neurons innervating skin and mantle shelf of Aplysia, J. Neurophysiol. 37:1041–1064.PubMedGoogle Scholar
  11. Byrne, J., Castellucci, V. F., and Kandel, E. R., 1978, Contribution of individual mechanoreceptor sensory neurons to defensive gill-withdrawal reflex in Aplysia, J. Neurophysiol. 41:418–431.PubMedGoogle Scholar
  12. Carew, T. J., Walters, E. T., and Kandel, E. R., 1981, Classical conditioning in a simple withdrawal reflex in Aplysia californica, J. Neurosci. 1:1426–1437.PubMedGoogle Scholar
  13. Carew, T. J., Hawkins, R. D., and Kandel, E. R., 1983, Differential classical conditioning of a defensive withdrawal reflex in Aplysia californica, Science 219:397–400.PubMedCrossRefGoogle Scholar
  14. Carew, T. J., Abrams, T. W., Hawkins, R. D., and Kandel, E. R., 1984, A test of Hebb’s postulate at identified synapses which mediate classical conditioning in Aplysia, J. Neurosci. 4:1217–1224.PubMedGoogle Scholar
  15. Castellucci, V. F., and Kandel, E. R., 1976, Presynaptic facilitation as a mechanism for behavioral sensitization in Aplysia, Science 194:1176–1178.PubMedCrossRefGoogle Scholar
  16. Castellucci, V. F., Kandel, E. R., Schwartz, J. H., Wilson, F. D., Nairn, A. C., and Greengard, P., 1980, Intracellular injection of the catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia, Proc. Natl. Acad. Sci. U.S.A. 77:7492–7496.PubMedCrossRefGoogle Scholar
  17. Castellucci, V. F., Bernier, L., Schwartz, J. H., and Kandel, E. R., 1983, Persistent activation of adenylate cyclase underlies the time course of short-term sensitization in Aplysia, Soc. Neurosci. Abstr. 9:169.Google Scholar
  18. Clark, G. A., McCormick, D. A., Lavond, D. G., Thompson, R. F., 1984, Effects of lesions of cerebellar nuclei on conditioned behavioral and hippocampal neuronal responses, Brain Res. 291:125–136.PubMedCrossRefGoogle Scholar
  19. Crow, T. J., and Alkon, D. L., 1978, Retention of an associative behavioral change in Hermissenda, Science 201:1239–1241.PubMedCrossRefGoogle Scholar
  20. Davis, W. J., Villet, J., Lee, D., Rigler, M., Gillette, R., and Prince, E., 1980, Selective and differential avoidance learning in the feeding and withdrawal behavior of Pleurobranchaea californica, J. Comp. Physiol. 138:157–165.CrossRefGoogle Scholar
  21. Dudai, Y., and Zvi, S., 1984, Adenylate cyclase in the Drosophila memory mutant rutabaga displays an altered Ca2+ sensitivity, Neurosci. Letters 47:119–124.CrossRefGoogle Scholar
  22. Gelperin, A., 1975, Rapid food-aversion learning by a terrestrial mollusk, Science 189:567–570.PubMedCrossRefGoogle Scholar
  23. Glanzman, D. L., Abrams, T. W., Hawkins, R. D., and Kandel, E. R., 1984, Extracts of L29 intemeurons produce spike-broadening in sensory neurons of Aplysia, Soc. Neurosci. Abstr. 10:510.Google Scholar
  24. Gold, M. R., and Cohen, D. H., 1981, Modification of the discharge of vagal cardiac neurons during learned heart rate change, Science 214:345–347.PubMedCrossRefGoogle Scholar
  25. Hawkins, R. D., and Abrams, T. W., 1984, Evidence that activity-dependent facilitation underlying classical conditioning in Aplysia involves modulation of the same ionic current as normal presynaptic facilitation, Soc Neurosci. Abstr. 10:268.Google Scholar
  26. Hawkins, R. D., Castellucci, V. F., and Kandel, E. R., 1981a, Intemeurons involved in mediation and modulation of the gill-withdrawal reflex in Aplysia. I. Identification and characterization, J. Neu-rophysiol. 45:304–314.Google Scholar
  27. Hawkins, R. D., Castellucci, V. F., and Kandel, E. R., 1981b, Intemeurons involved in mediation and modulation of the gill-withdrawal reflex in Aplysia. II. Identified neurons produce heterosynaptic facilitation contributing to behavioral sensitization, J. Neurophysiol. 45:315–326.PubMedGoogle Scholar
  28. Hawkins, R. D., Abrams, T. W., Carew, T. J., and Kandel, E. R., 1983a, A cellular mechanism of classical conditioning in Aplysia: Activity-dependent amplification of presynaptic facilitation, Science 219:400–405.PubMedCrossRefGoogle Scholar
  29. Hawkins, R. D., Carew, T. J., and Kandel, E. R., 1983b, Effects of interstimulus interval and contingency on classical conditioning in Aplysia, Soc. Neurosci. Abstr. 9:168.Google Scholar
  30. Hebb, D. O., 1949, The Organization of Behavior, New York, Wiley & Sons, Inc.Google Scholar
  31. Horridge, G. A., 1962, Learning of leg position by headless insects, Nature (London) 193:697–698.CrossRefGoogle Scholar
  32. Hoyle, G., 1980, Learning, usual natural reinforcements, in insect preparations that permit cellular neuronal analysis, J. Neurophysiol. 11:323–354.Google Scholar
  33. Kamin, L. J., 1969, Predictability, surprise, attention, and conditioning, in: Punishment and Aversive Behavior (B. A. Campbell and R. M. Church, eds.), Appleton-Century-Crofts, New York, pp. 279–296.Google Scholar
  34. Kandel, E. R., and Schwartz, J. H., 1982, Molecular biology of an elementary form of learning: Modulation of transmitter release by cyclic AMP, Science 218:433–443.PubMedCrossRefGoogle Scholar
  35. Kandel, E. R., Abrams, T., Bernier, L., Carew, T. J., Hawkins, R. D., and Schwartz, J. H., 1983, Classical conditioning and sensitization share aspects of the same molecular cascade in Aplysia, Cold Spring Harbor Symp. Quant. Biol. 48:821–830.CrossRefGoogle Scholar
  36. Kistler, H. B., Jr., Hawkins, R. D., Koester, J., Steinbusch, H. W. M., Kandel, E. R., and Schwartz, J. H., 1985, Distribution of serotonin-immunoreactive cell bodies and processes in the abdominal ganglion of mature Aplysia, J. Neurosci. 5:72–80.Google Scholar
  37. Klein, M., and Kandel, E. R., 1978, Presynaptic modulation of voltage-dependent Ca2+ current: Mechanism for behavioral sensitization in Aplysia californica, Proc. Natl. Acad. Sci. U.S.A. 75:3512–3516.PubMedCrossRefGoogle Scholar
  38. Klein, M., and Kandel, E. R., 1980, Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia, Proc. Natl. Acad. Sci. U.S.A. 77:6912–6916.CrossRefGoogle Scholar
  39. Klein, M., Shapiro, E., and Kandel, E. R., 1981, Synaptic plasticity and the modulation of the Ca2+ current, J. Exp. Biol. 89:117–157.Google Scholar
  40. Livingstone, M. S., Sziber, P. P., and Quinn, W. G., 1984, Loss of calcium/calmodulin sensitivity responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant, Cell 37:205–215.PubMedCrossRefGoogle Scholar
  41. Lukowiak, K., and Sahley, C., 1981, The in vitro classical conditioning of the gill withdrawal reflex of Aplysia californica, Science 212:1516–1518.PubMedCrossRefGoogle Scholar
  42. Mpitsos, G. J., and Collins, S. D., 1975, Learning: Rapid aversive conditioning in the gastropod mollusk Pleurobranchaea, Science 188:954–957.PubMedCrossRefGoogle Scholar
  43. Ocorr, K. A., Walters, E. T., and Byrne, J. H., 1983, Associative conditioning analog in Aplysia tail sensory neurons selectively increases cAMP content, Soc. Neurosci. Abstr. 9:169.Google Scholar
  44. Pavlov, I. P., 1927, Conditioned Reflexes, Oxford University Press.Google Scholar
  45. Perlman, A. J., 1979, Central and peripheral control of siphon withdrawal reflex in Aplysia californica, J. Neurophysiol. 42:510–529.PubMedGoogle Scholar
  46. Pinsker, H., Kupfermann, I., Castellucci, V., and Kandel, E. R., 1970, Habituation and dishabituation of the gill-withdrawal reflex in Aplysia, Science 167:1740–1742.PubMedCrossRefGoogle Scholar
  47. Pinsker, H. M., Hening, W. A., Carew, T. J., and Kandel, E. R., 1973, Long-term sensitization of a defensive withdrawal reflex in Aplysia, Science 182:1039–1042.PubMedCrossRefGoogle Scholar
  48. Quinn, W. G., Harris, W. A., and Benzer, S., 1974, Conditioned behavior in Drosophila melanogaster, Proc. Natl. Acad. Sci. U.S.A. 71:708–712.PubMedCrossRefGoogle Scholar
  49. Rescorla, R. A., and Wagner, A. R., 1972, A theory of Pavlovian conditioning: Variations in the effectiveness of reinforcement and nonreinforcement, in: Classical Conditioning II: Current research and theory (A. H. Black and W. F. Prokasy, eds.), Appleton-Century-Crofts, New York, p. 64–99.Google Scholar
  50. Rodbell, M., 1980, The role of hormone receptors and GTP-regulatory proteins in membrane transduction, Nature (London) 284:17–22.CrossRefGoogle Scholar
  51. Sahley, C., Rudy, J. W., and Gelperin, A., 1981, An analysis of associative learning in a terrestrial mollusc. I. Higher-order conditioning, blocking, and a transient US pre-exposure effect, J. Comp. Physiol. 144:1–8.CrossRefGoogle Scholar
  52. Salter, R. S., Krinks, M. H., Klee, C. B., and Neer, E. J., 1981, Calmodulin activates the isolated catalytic unit of brain adenylate cyclase, J. Biol. Chem. 256:9830–9833.PubMedGoogle Scholar
  53. Siegelbaum, S., Camardo, J. S., and Kandel, E. R., 1982, Serotonin and cAMP close single K+ channels in Aplysia sensory neurones, Nature (London) 299:413–417.CrossRefGoogle Scholar
  54. Walters, E. T., and Byrne, J. H., 1983, Associative conditioning of single sensory neurons suggests a cellular mechanism for learning, Science 219:405–408.PubMedCrossRefGoogle Scholar
  55. Walters, E. T., Carew, T. J., and Kandel, E. R., 1979, Classical conditioning in Aplysia californica, Proc. Natl. Acad. Sci. USA 76:6675–6679.PubMedCrossRefGoogle Scholar
  56. Walters, E. T., Byrne, J. H., Carew, T. J., and Kandel, E. R., 1983, Mechanoefferent neurons innervating the tail of Aplysia: II. Modulation by sensitizing stimulation, J. Neurophysiol. 50:1543–1559.PubMedGoogle Scholar
  57. Woolacott, M. H., and Hoyle, G., 1977, Neural events underlying learning in insects: Changes in pacemaker, Proc. R. Soc. London Ser. B 195:395–415.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Thomas W. Abrams
    • 1
    • 2
  1. 1.Center for Neurobiology and Behavior, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  2. 2.Howard Hughes Medical InstituteNew YorkUSA

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