Journal of Computational Neuroscience

, Volume 2, Issue 4, pp 335–343 | Cite as

A model for long-term potentiation and depression

  • M. Migliore
  • F. Alicata
  • G. F. Ayala


A computational model of long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus is presented. The model assumes the existence of retrograde signals, is in good agreement with several experimental data on LTP, LTD, and their pharmacological manipulations, and shows how a simple kinetic scheme can capture the essential characteristics of the processes involved in LTP and LTD. We propose that LTP and LTD could be two different but conceptually similar processes, induced by the same class of retrograde signals, and maintained by two distinct mechanisms. An interpretation of a number of experiments in terms of the molecular processes involved in LTP and LTD induction and maintenance, and the roles of a retrograde signal are presented and discussed.


computer simulations kinetic model LTD LTP retrograde messenger 


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  1. Bienenstock EL, Cooper LN, Munro PW (1982) Theory for the development of neuron selectivity: Orientation specificity and binocular interaction in visual cortex.J. Neurosci. 2:32–48.Google Scholar
  2. Bliss TVP, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path.J. Physiol. 232:331–356.Google Scholar
  3. Bredt DS, Snyder SH (1992) Nitric oxide: A novel neuronal messenger.Neuron 8:3–11.Google Scholar
  4. Brown TH, Zador AM (1990) The Hippocampus. In: GM Shepherd, ed. The Synaptic Organization of the Brain. Oxford University Press, New York. pp. 346–388.Google Scholar
  5. Dudek SM, Bear MF (1992) Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade.Proc. Natl. Acad. Sci. USA 89:4363–4367.Google Scholar
  6. Dundwiddie T, Lynch GS (1978) Long-term potentiation and depression of synaptic response in rat hippocampus: localization and frequency dependence.J. Physiol. 276:353–368.Google Scholar
  7. Edelstein-Keshet L (1988) Mathematical models in biology. Random House, New York.Google Scholar
  8. Haley JE, Wilcox GL, Chapman PF (1992) The role of nitric oxide in hippocampal long-term potentiation.Neuron 8:211–216.Google Scholar
  9. Izumi Y, Clifford DB, Zorumski CF (1992) Inhibition of long-term potentiation by NMDA-mediated nitric oxide release.Science 257:1273–1276.Google Scholar
  10. Lisman J (1989) A mechanism for the Hebb and the anti-Hebb process underlying learning and memory.Proc. Natl, Acad. Sci. USA 86:9574–9578.Google Scholar
  11. Malenka RC (1993) Long-term depression: Not so depressing after all.Proc. Natl. Acad. Sci. USA 90:3121–3123.Google Scholar
  12. Migliore M, Ayala GF (1993) A kinetic model of short- and long-term potentiation.Neural Comput. 5:636–647.Google Scholar
  13. O'Dell TJ, Hawkins RD, Kandel ER, Arancio O (1991) Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger.Proc. Natl. Acad. Sci. USA 88:11285–11289.Google Scholar
  14. Schuman M, Madison DV (1991) A requirement for the intercellular messenger nitric oxide in long-term potentiation.Science 254:1503–1506.Google Scholar
  15. Segel Lee A (1991) Biological Kinetics, Cambridge University Press, Cambridge.Google Scholar
  16. Shibuki K, Okada D (1991) Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum.Nature 349:326–328.Google Scholar
  17. Stevens CF, Wang Y (1993) Reversal of long-term potentiation by inhibitors of haem oxygenase.Nature 364:147–149.Google Scholar
  18. Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH (1993) Carbon monoxide: A putative neural messenger.Science 259:381–384.Google Scholar

Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • M. Migliore
    • 1
  • F. Alicata
    • 2
  • G. F. Ayala
    • 2
    • 3
  1. 1.Institute for Interdisciplinary Applications of Physics, National Research CouncilPalermoItaly
  2. 2.OASI Institute for Research and Treatment of Mental Retardation and Brain AgingTroinaItaly
  3. 3.Chair of Psychophysiology, Department of PsychologyUniversity of PalermoPalermoItaly

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