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. 1999 Sep;77(3):1234–1243. doi: 10.1016/S0006-3495(99)76975-4

Long-term potentiation and depression induced by a stochastic conditioning of a model synapse.

M Migliore 1, P Lansky 1
PMCID: PMC1300415  PMID: 10465738

Abstract

Protracted presynaptic activity can induce long-term potentiation (LTP) or long-term depression (LTD) of the synaptic strength. However, virtually all the experiments testing how LTP and LTD depend on the conditioning input are carried out with trains of stimuli at constant frequencies, whereas neurons in vivo most likely experience a stochastic variation of interstimulus intervals. We used a computational model of synaptic transmission to test if and to what extent the stochastic fluctuations of an input signal could alter the probability to change the state of a synapse. We found that, even if the mean stimulation frequency was maintained constant, the probability to induce LTD and LTP could be a function of the temporal variation of the input activity. This mechanism, which depends only on the statistical properties of the input and not on the onset of additional biochemical mechanisms, is not usually considered in the experiments, but it could have an important role to determine the amount of LTP/LTD induction in vivo. In response to a change in the distribution of the interstimulus intervals, as measured by the coefficient of variation, a synapse could be easily adapted to inputs that might require immediate attention, with a shift of the input thresholds required to elicit LTD or LTP, which are restored to their initial conditions as soon as the input pattern returns to the original temporal distribution.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott L. F., Varela J. A., Sen K., Nelson S. B. Synaptic depression and cortical gain control. Science. 1997 Jan 10;275(5297):220–224. doi: 10.1126/science.275.5297.221. [DOI] [PubMed] [Google Scholar]
  2. Abraham W. C., Bear M. F. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 1996 Apr;19(4):126–130. doi: 10.1016/s0166-2236(96)80018-x. [DOI] [PubMed] [Google Scholar]
  3. Abraham W. C., Huggett A. Induction and reversal of long-term potentiation by repeated high-frequency stimulation in rat hippocampal slices. Hippocampus. 1997;7(2):137–145. doi: 10.1002/(SICI)1098-1063(1997)7:2<137::AID-HIPO3>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  4. Aihara T., Tsukada M., Crair M. C., Shinomoto S. Stimulus-dependent induction of long-term potentiation in CA1 area of the hippocampus: experiment and model. Hippocampus. 1997;7(4):416–426. doi: 10.1002/(SICI)1098-1063(1997)7:4<416::AID-HIPO7>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  5. Artola A., Singer W. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends Neurosci. 1993 Nov;16(11):480–487. doi: 10.1016/0166-2236(93)90081-v. [DOI] [PubMed] [Google Scholar]
  6. Bear M. F. Mechanism for a sliding synaptic modification threshold. Neuron. 1995 Jul;15(1):1–4. doi: 10.1016/0896-6273(95)90056-x. [DOI] [PubMed] [Google Scholar]
  7. Bienenstock E. L., Cooper L. N., Munro P. W. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J Neurosci. 1982 Jan;2(1):32–48. doi: 10.1523/JNEUROSCI.02-01-00032.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cohen A. S., Abraham W. C. Facilitation of long-term potentiation by prior activation of metabotropic glutamate receptors. J Neurophysiol. 1996 Aug;76(2):953–962. doi: 10.1152/jn.1996.76.2.953. [DOI] [PubMed] [Google Scholar]
  9. Coomber C. J. Site-selective autophosphorylation of Ca2+/calmodulin-dependent protein kinase II as a synaptic encoding mechanism. Neural Comput. 1998 Oct 1;10(7):1653–1678. doi: 10.1162/089976698300017070. [DOI] [PubMed] [Google Scholar]
  10. Coussens C. M., Kerr D. S., Abraham W. C. Glucocorticoid receptor activation lowers the threshold for NMDA-receptor-dependent homosynaptic long-term depression in the hippocampus through activation of voltage-dependent calcium channels. J Neurophysiol. 1997 Jul;78(1):1–9. doi: 10.1152/jn.1997.78.1.1. [DOI] [PubMed] [Google Scholar]
  11. Dobrunz L. E., Stevens C. F. Response of hippocampal synapses to natural stimulation patterns. Neuron. 1999 Jan;22(1):157–166. doi: 10.1016/s0896-6273(00)80687-x. [DOI] [PubMed] [Google Scholar]
  12. Dudek S. M., Bear M. F. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4363–4367. doi: 10.1073/pnas.89.10.4363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fagnou D. D., Tuchek J. M. The biochemistry of learning and memory. Mol Cell Biochem. 1995 Aug-Sep;149-150:279–286. doi: 10.1007/BF01076589. [DOI] [PubMed] [Google Scholar]
  14. Fenton A. A., Muller R. U. Place cell discharge is extremely variable during individual passes of the rat through the firing field. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3182–3187. doi: 10.1073/pnas.95.6.3182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gold J. I., Bear M. F. A model of dendritic spine Ca2+ concentration exploring possible bases for a sliding synaptic modification threshold. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3941–3945. doi: 10.1073/pnas.91.9.3941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hajós M., Sharp T. 5-HT neurones--bursting with information? Trends Neurosci. 1997 Jun;20(6):244–244. doi: 10.1016/s0166-2236(97)86999-8. [DOI] [PubMed] [Google Scholar]
  17. Huerta P. T., Lisman J. E. Bidirectional synaptic plasticity induced by a single burst during cholinergic theta oscillation in CA1 in vitro. Neuron. 1995 Nov;15(5):1053–1063. doi: 10.1016/0896-6273(95)90094-2. [DOI] [PubMed] [Google Scholar]
  18. Johnson D. H. Point process models of single-neuron discharges. J Comput Neurosci. 1996 Dec;3(4):275–299. doi: 10.1007/BF00161089. [DOI] [PubMed] [Google Scholar]
  19. Kirkwood A., Rioult M. C., Bear M. F. Experience-dependent modification of synaptic plasticity in visual cortex. Nature. 1996 Jun 6;381(6582):526–528. doi: 10.1038/381526a0. [DOI] [PubMed] [Google Scholar]
  20. Larson J., Lynch G. Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events. Science. 1986 May 23;232(4753):985–988. doi: 10.1126/science.3704635. [DOI] [PubMed] [Google Scholar]
  21. Larson J., Wong D., Lynch G. Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res. 1986 Mar 19;368(2):347–350. doi: 10.1016/0006-8993(86)90579-2. [DOI] [PubMed] [Google Scholar]
  22. Lisman J. E. Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci. 1997 Jan;20(1):38–43. doi: 10.1016/S0166-2236(96)10070-9. [DOI] [PubMed] [Google Scholar]
  23. Lisman J. E., Goldring M. A. Feasibility of long-term storage of graded information by the Ca2+/calmodulin-dependent protein kinase molecules of the postsynaptic density. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5320–5324. doi: 10.1073/pnas.85.14.5320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lisman J. A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9574–9578. doi: 10.1073/pnas.86.23.9574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lisman J. The CaM kinase II hypothesis for the storage of synaptic memory. Trends Neurosci. 1994 Oct;17(10):406–412. doi: 10.1016/0166-2236(94)90014-0. [DOI] [PubMed] [Google Scholar]
  26. Markram H., Tsodyks M. Redistribution of synaptic efficacy between neocortical pyramidal neurons. Nature. 1996 Aug 29;382(6594):807–810. doi: 10.1038/382807a0. [DOI] [PubMed] [Google Scholar]
  27. Migliore M., Alicata F., Ayala G. F. A model for long-term potentiation and depression. J Comput Neurosci. 1995 Dec;2(4):335–343. doi: 10.1007/BF00961444. [DOI] [PubMed] [Google Scholar]
  28. Petersen C. C., Malenka R. C., Nicoll R. A., Hopfield J. J. All-or-none potentiation at CA3-CA1 synapses. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4732–4737. doi: 10.1073/pnas.95.8.4732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rose G. M., Dunwiddie T. V. Induction of hippocampal long-term potentiation using physiologically patterned stimulation. Neurosci Lett. 1986 Sep 12;69(3):244–248. doi: 10.1016/0304-3940(86)90487-8. [DOI] [PubMed] [Google Scholar]
  30. Soderling T. R. Calcium/calmodulin-dependent protein kinase II: role in learning and memory. Mol Cell Biochem. 1993 Nov;127-128:93–101. doi: 10.1007/BF01076760. [DOI] [PubMed] [Google Scholar]
  31. Softky W. R., Koch C. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J Neurosci. 1993 Jan;13(1):334–350. doi: 10.1523/JNEUROSCI.13-01-00334.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stanton P. K. LTD, LTP, and the sliding threshold for long-term synaptic plasticity. Hippocampus. 1996;6(1):35–42. doi: 10.1002/(SICI)1098-1063(1996)6:1<35::AID-HIPO7>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  33. Stanton P. K. Transient protein kinase C activation primes long-term depression and suppresses long-term potentiation of synaptic transmission in hippocampus. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1724–1728. doi: 10.1073/pnas.92.5.1724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tsodyks M., Pawelzik K., Markram H. Neural networks with dynamic synapses. Neural Comput. 1998 May 15;10(4):821–835. doi: 10.1162/089976698300017502. [DOI] [PubMed] [Google Scholar]
  35. Tsukada M., Aihara T., Mizuno M., Kato H., Ito K. Temporal pattern sensitivity of long-term potentiation in hippocampal CA1 neurons. Biol Cybern. 1994;70(6):495–503. doi: 10.1007/BF00198802. [DOI] [PubMed] [Google Scholar]
  36. Varela J. A., Sen K., Gibson J., Fost J., Abbott L. F., Nelson S. B. A quantitative description of short-term plasticity at excitatory synapses in layer 2/3 of rat primary visual cortex. J Neurosci. 1997 Oct 15;17(20):7926–7940. doi: 10.1523/JNEUROSCI.17-20-07926.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wilbur W. J., Rinzel J. A theoretical basis for large coefficient of variation and bimodality in neuronal interspike interval distributions. J Theor Biol. 1983 Nov 21;105(2):345–368. doi: 10.1016/s0022-5193(83)80013-7. [DOI] [PubMed] [Google Scholar]

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