Current problems of synaptic plasticity

Cover Page

Cite item

Full Text


The present review focuses on the results of modern studies confirming the last century ideas about the effect of neuron discharge on the effectiveness of its synaptic inputs. This concept is being developed now at the receptor, channel and intracellular levels, which allows to reveal the special role of calcium ions in the activation of a number of cascades leading to transient or long-lasting changes in synaptic transmission. An important role of various physiologically active compounds that affect synaptic plasticity and, through it, the cognitive processes in humans is emphasized, which has not only fundamental, but also applied significance. Cellular and receptor targets of nootropic drugs aimed at the correction of various types of cognitive impairment are specifically considered

About the authors

Vladimir G. Skrebitsky

Research Center of Neurology

Author for correspondence.
Russian Federation, Moscow

Irina N. Sharonova

Research Center of Neurology

ORCID iD: 0000-0001-9955-1870

D. Sci. (Biol.), leading researcher, Laboratory of functional synaptology

Russian Federation, Moscow


  1. Hebb O.D. The Organization of Behavior. NY: Wiley, 1949. 335 p.
  2. Brindley G.S. The classification of modifiable synapses and their use in models for conditioning. Proc. Royal Soc Lond B Biol Sci 1967; 168: 361-367. doi: 10.1098/rspb.1967.0070.
  3. Gerbrandt L.K., Skrebitsky V.G., Burešová O., Bureš J.Plastic changes of unit activity induced by tactile stimuli followed by electrical stimulation of single hippocampal and reticular neurons. Neuropsychologia 1968; 6: 3-10. DOI. org/10.1016/0028-3932(68)90034-1. doi: 10.1016/0028-3932(68)90034-1.
  4. Rusinova E.V., Skrebitskii V.G. Vliyanie razryada nejrona na ehffektivnost’ ego sinapticheskikh vkhodov. [The influence of neuronal discharge on the effectiveness of its synaptic inputs]. Zhurnal Vysshey Nervnoy Deiatel’njsti Im I.P. Pavlova 1975; 25(6): 1312-1315. PMID: 1210783. (In Russ.)
  5. Baranyi A., Szente M.B. Long-lasting potentiation of synaptic transmission requires postsynaptic modifications in the neocortex. Brain Res 1987; 423(1-2): 378-384. doi: 10.1016/0006-8993(87)90867-5. PMID: 2823992.
  6. Skrebitsky V.G., Chepkova A.N. Hebbian synapses in cortical and hippocampal pathways. Rev Neurosci 1998; 9(4): 243-264. doi: 10.1515/REVNEURO. 1998.9.4.243. PMID: 9886140.
  7. Bliss T.V., Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 1973; 232(2): 331-356. doi: 10.1113/jphysiol.1973.sp010273. PMID: 4727084.
  8. Bliss T.V., Collingridge G.L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361(6407): 31-39. doi: 10.1038/361031a0. PMID: 8421494.
  9. Bliss T.V., Collingridge G.L., Morris R.G. Synaptic plasticity in health and disease: introduction and overview. Philos Trans R Soc Lond B Biol Sci 2013; 369(1633): 20130129. doi: 10.1098/rstb.2013.0129. PMID: 24298133.
  10. Voronin L.L. Long-term potentiation in the hippocampus. Neuroscience 1983; 10(4): 1051-1069. doi: 10.1016/0306-4522(83)90099-4. PMID: 6141538.
  11. Sastry B.R., Goh J.W., Auyeung A. Associative induction of posttetanic and long-term potentiation in CA1 neurons of rat hippocampus. Science 1986; 232(4753): 988-990. doi: 10.1126/science.3010459. PMID: 3010459.
  12. Kelso S.R., Ganong A.H., Brown T.H. Hebbian synapses in hippocampus. Proc Natl Acad Sci USA 1986; 83(14): 5326-5330. doi: 10.1073/pnas.83.14.5326. PMID: 3460096.
  13. Lodge D., Watkins J.C., Bortolotto Z.A., Jane D.E, Volianskis A. The 1980s: D-AP5,LTP and a decade of NMDA receptor discoveries. Neurochem Res 2018. doi: 10.1007/s11064-018-2640-6. PMID: 30284673.
  14. Morris R.G. NMDA receptors and memory encoding. Neuropharmacology 2013; 74: 32-40. doi: 10.1016/j.neuropharm.2013.04.014. PMID: 23628345.
  15. Magee J.C., Johnston D. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 1997; 275(5297):209-213. doi: 10.1126/science.275.5297.209. PMID: 8985013.
  16. Markram H., Lübke J., Frotscher M., Sakmann B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 1997; 275(5297): 213-215. doi: 10.1126/science.275.5297.213. PMID: 8985014.
  17. Bliss T.V., Douglas R.M., Errington M.L., Lynch M.A. Correlation between long-term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats. J Physiol 1986; 377: 391-408. doi: 10.1113/jphysiol. 1986.sp016193. PMID: 2879038.
  18. Maren S., Tocco G., Standley S., Baudry M., Thompson R.F. Postsynaptic factors in the expression of long-term potentiation (LTP): increased glutamate receptor binding following LTP induction in vivo. Proc Natl Acad Sci USA 1993; 90(20): 9654-9658. doi: 10.1073/pnas.90.20.9654. PMID: 8415757.
  19. Frey U., Krug M., Reymann K.G., Matthies H. Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res 1988; 452 (1-2): 57-65. doi: 10.1016/0006- 8993(88)90008-X. PMID: 3401749.
  20. Frey U., Huang Y.Y., Kandel E.R. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science 1993; 260 (5114): 1661-1664. doi: 10.1126/science.8389057. PMID: 8389057.
  21. Mayford M., Siegelbaum S.A., Kandel E.R. Synapses and memory storage. Cold Spring Harb Perspect Biol 2012; 4(6). doi: 10.1101/cshperspect.a005751. PMID: 2249638.
  22. Danysz W., Zajaczkowski W., Parsons C.G. Modulation of learning processes by ionotropic glutamate receptor ligands. Behav Pharmacol 1995; 6 (5–6): 455- 474. PMID: 11224354.
  23. Barnes C.A. Involvement of LTP in memory: are we “searching under the street light”? Neuron 1995; 15 (4): 751-754. doi: 10.1016/0896-6273(95)90166-3. PMID: 7576624.
  24. Mayford M., Abel T., Kandel E.R. Transgenic approaches to cognition. Curr Opin Neurobiol 1995; 5(2): 141-148. doi: 10.1016/0959-4388(95)80019-0. PMID: 7620300.
  25. Wigström H., Gustafsson B. Large long-lasting potentiation in the dentate gyrus in vitro during blockade of inhibition. Brain Res 1983; 275(1): 153-158. doi: 10.1016/0006-8993(83)90428-6. PMID: 6313124.
  26. Ormond J., Woodin M.A. Disinhibition mediates a form of hippocampal long-term potentiation in area CA1. PLoS One 2009; 4(9): e7224. DOI: 10.1371/ journal.pone.0007224. PMID: 19787049.
  27. Davies C.H., Collingridge G.L. The physiological regulation of synaptic inhibition by GABAB autoreceptors in rat hippocampus. J Physiol 1993; 472: 245- 265. doi: 10.1113/jphysiol.1993.sp019945. PMID: 8145143.
  28. Fedorov N.B., Sergeeva O.A., Skrebitsky V.G. Priming stimulation facilitates Hebb-type plasticity in the Schaffer collateral-commissural pathways of the mouse hippocampus. Exp Brain Res 1993; 94(2): 270-272. DOI: 10.1007/ BF00230295. PMID: 8359243.
  29. Vinogradova O.S. Gippokamp i pamyat’ [Hippocampus and memory]. М.: Nauka, 1975. 333 p. (In Russ.)
  30. Larson J., Munkácsy E. Theta-burst LTP. Brain Res 2015; 1621: 38-50. doi: 10.1016/j.brainres.2014.10.034. PMID: 25452022.
  31. Skrebitsky V.G. Nonspecific influences on neuronal firing in the central visual pathway. Exp Brain Res 1969; 9(4): 269-283. doi: 10.1007/BF00235239. PMID: 5364413.
  32. Skrebitsky V.G., Sharonova I.N. Reticular suppression of flash-evoked IPSPs in visual cortex neurons. Brain Res 1976; 111(1): 67-78. doi: 10.1016/0006- 8993(76)91049-0. PMID: 953705.
  33. Klausberger T., Magill P.J., Márton L.F., Roberts J.D., Cobden P.M., Buzsáki G., Somogyi P. Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature 2003; 421(6925): 844-848. doi: 10.1038/nature01374. PMID: 12594513.
  34. Dykes R.W. Mechanisms controlling neuronal plasticity in somatosensory cortex. Can J Physiol Pharmacol 1997; 75(5): 535-545. doi: 10.1139/y97-089. PMID: 9250389.
  35. Pavlov I.P. Lektsii o rabote bol’shikh polushariy mozga [Lectures on functions of cerebral hemispheres]. Complete collected works. V.4. Мoscow: AN SSSR, 1951. 452 p.
  36. Sara S.J. Noradrenergic modulation of selective attention: its role in memory retrieval. Ann N Y Acad Sci 1985; 444: 178-193. doi: 10.1111/j.1749-6632.1985. tb37588.x. PMID: 2990290.
  37. Skrebitsky V.G., Chepkova A.N., Sharonova I.N. Reticular suppression of cortical inhibitory postsynaptic potentials. In: Hobson J.A., Brzier M.A. (Eds) Reticular Formation Revisited. NY: Raven Press, 1980: 67-78.
  38. Doze V.A., Cohen G.A., Madison D.V. Synaptic localization of adrenergic disinhibition in the rat hippocampus. Neuron 1991; 6(6): 889-900. doi: 10.1016/0896-6273(91)90229-S. PMID: 1675862.
  39. Griffith J.S. A theory of the nature of memory. Nature 1966; 211(5054): 1160- 1163. doi: 10.1038/2111160a0. PMID: 5970018.
  40. Brown T.H., Chapman P.F., Kairiss E.W., Keenan C.L. Long-term synaptic potentiation. Science 1988; 242 (4879): 724-728. doi: 10.1126/science.2903551. PMID: 2903551.
  41. Solari N., Hangya B. Cholinergic modulation of spatial learning, memory and navigation. Eur J Neurosci 2018; 48(5): 2199-2230. doi: 10.1111/ejn.14089. PMID: 30055067.
  42. Lin Y.W., Min M.Y., Chiu T.H., Yang H.W. Enhancement of associative longterm potentiation by activation of beta-adrenergic receptors at CA1 synapses in rat hippocampal slices. J Neurosci. 2003, 23(10): 4173-4181. DOI: 10.1523/ JNEUROSCI.23-10-04173.2003. PMID: 12764105.
  43. O’Dell T.J., Connor S.A., Guglietta R., Nguyen P.V. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus. Learn Mem 2015; 22(9): 461-471. doi: 10.1101/lm.031088.113. PMID: 26286656.
  44. Hansen N., Manahan-Vaughan D. Hippocampal long-term potentiation that is elicited by perforant path stimulation or that occurs in conjunction with spatial learning is tightly controlled by beta-adrenoreceptors and the locus coeruleus. Hippocampus 2015: 25(11): 1285-1298. doi: 10.1002/hipo.22436. PMID: 25727388.
  45. Takeuchi T., Duszkiewicz A.J., Sonneborn A. et al. Locus coeruleus and dopaminergic consolidation of everyday memory. Nature 2016; 537: 357-362. doi: 10.1038/nature19325. PMID: 27602521.
  46. Wei X., Ma T., Cheng Y. et al. Dopamine D1 or D2 receptor-expressing neurons in the central nervous system. Addict Biol 2018; 23(2): 569-584. doi: 10.1111/adb.12512. PMID: 28436559.
  47. Hammad H., Wagner J.J. Dopamine-mediated disinhibition in the CA1 region of rat hippocampus via D3 receptor activation. J Pharmacol Exp Ther 2006; 316(1):113-120. doi: 10.1124/jpet.105.091579. PMID: 16162819.
  48. Lemon N., Manahan-Vaughan D. Dopamine D1/D5 receptors gate the acquisition of novel information through hippocampal long-term potentiation and long-term depression. J Neurosci 2006; 26(29): 7723-7729. DOI: 10.1523/ JNEUROSCI.1454-06.2006. PMID: 16855100.
  49. Lin J.S., Anaclet C., Sergeeva O.A., Haas H.L. The waking brain: an update. Cell Mol Life Sci 2011; 68(15): 2499-2512. doi: 10.1007/s00018-011-0631-8. Review. PMID: 21318261.
  50. Vorobjev V.S, Sharonova I.N., Walsh I.B., Haas H.L. Histamine potentiates N-methyl-D-aspartate responses in acutely isolated hippocampal neurons. Neuron 1993; 11(5): 837-844. doi: 10.1016/0896-6273(93)90113-6. PMID: 8240807.
  51. Kovacs G.L, De Wied D. Peptidergic modulation of learning and memory processes. Pharmacol Rev 1994; 46(3): 269-291. PMID: 7831381.
  52. Chepkova A.N. Vliyanie vasopressina na svoystva dlitel’noy posttetanicheskoy potentsiatsii v srezakh gippokampa [Effect of vasopressin on the characteristics of prolonged posttetanic potentiation in hippocampal slices]. Zhurnal Vysshey Nervnoy Deiatel’nosti Im I.P. Pavlova 1981; 31(2): 427-430. PMID: 7269796. (In Russ.).
  53. Chepkova A.N., Skrebitskii V.G. Effects of some adrenergic drugs and neuropeptides on long-term potentiation in hippocampal slices. In: Ajmone Marsan C., Matthies H.(eds). Neuronal Plasticity and Memory Formation. NY: Raven Press, 1982: 255-263.
  54. Reijmers L.G., van Ree J.M., Spruijt B.M. et al. Vasopressin metabolites: a link between vasopressin and memory? Prog Brain Res 1998;119: 523-535. doi: 10.1016/S0079-6123(08)61591-5. PMID: 10074810.
  55. Rong X.W., Chen X.F., Du Y.C. Potentiation of synaptic transmission by neuropeptide AVP4-8 (ZNC(C)PR) in rat hippocampal slices. Neuroreport 1993; 4(9): 1135-1138. PMID: 8219041.
  56. van den Hooff P., Urban I.J., de Wied D. Vasopressin maintains long-term potentiation in rat lateral septum slices. Brain Res 1989; 505(2): 181-186. doi: 10.1016/0006-8993(89)91440-6. PMID: 2532055.
  57. Chepkova A.N., French P., De Wied D. et al. Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8). Brain Res 1995; 701(1-2): 255-566. doi: 10.1016/0006-8993(95)01006-7. PMID: 8925289.
  58. Ishihara K., Katsuki H., Kawabata A. et al. Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices. Brain Res 1991; 554(1-2): 203-208. doi: 10.1016/0006-8993(91)90190-7. PMID: 1933301.
  59. Matsuoka N., Kaneko S., Satoh M. Somatostatin augments long-term potentiation of the mossy fiber-CA3 system in guinea-pig hippocampal slices. Brain Res 1991; 553(2): 188-194. doi: 10.1016/0006-8993(91)90823-E. PMID: 1681981.
  60. Gudasheva Т.А. Teoreticheskiye osnovy i tekhnologii sozdaniya dipeptidnykh lekarstv [Theoretic basis and technologies of creating dipeptide drugs]. Izvestiya akademii nauk. Seriya khimicheskaya 2015; 9: 2012-2021. (In Russ.)
  61. Olpe H.R., Lynch G.S. The action of piracetam on the electrical activity of the hippocampal slice preparation: a field potential analysis. Eur J Pharmacol 1982; 80(4): 415-419. doi: 10.1016/0014-2999(82)90088-7. PMID: 7106192.
  62. Satoh M., Ishihara K., Katsuki H. Different susceptibilities of long-term potentiations in CA3 and CA1 regions of guinea pig hippocampal slices to nootropic drugs. Neurosci Lett 1988; 93(2-3): 236-241. doi: 10.1016/0304- 3940(88)90088-2. PMID: 2853846.
  63. Chepkova A.N., Doreuli N.V., Ostrovskaia R.U. et al. Sokhraneniye plasticheskikh svoystv sinapticheskoy peredachi v dolgozhivyshchikh srezakh gipppokampa pod deystviyem peptidnogo analoga piratsetama [Preservation of plastic properties of synaptic transmission in long-lasting hippocampal slices under the effects of a peptide analog of piracetam, L-pGlu-D-Ala-NH2]. Biull Eksp Biol Med 1990; 110(12): 602-604. PMID: 1964611. (In Russ.).
  64. Chepkova A.N., Doreulee N.V., Trofimov S.S. et al. Nootropic compound L-pyroglutamyl-D-alanine-amide restores hippocampal long-term potentiation impaired by exposure to ethanol in rats. Neurosci Lett 1995; 188(3): 163-166. doi: 10.1016/0304-3940(95)11421-R. PMID: 7609900.
  65. Ostrovskaia R.U., Gudasheva T.A., Voronina T.A., Seredenin S.B. Original’niy nootropniy I neyroprotektivniy dipeptide noopept (GVS-111) [The original novel nootropic and neuroprotective agent noopept]. Eksp Klin Farmakol 2002; 65(5): 66-72. PMID: 12596521. (In Russ.).
  66. Ostrovskaya R.U., Belnik A.P., Storozheva Z.I. [Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by beta-amyloid25-35 injection into Meynert basal nuclei of rats)]. Bull Exp Biol Med 2008; 146(1): 77- 80. PMID: 19145356. (In Russ.).
  67. Jia X., Gharibyan A.L., Öhman A. et al. Neuroprotective and nootropic drug noopept rescues α-synuclein amyloid cytotoxicity. J Mol Biol 2011; 414(5): 699- 712. doi: 10.1016/j.jmb.2011.09.044. PMID: 21986202.
  68. Bochkarev V.К., Teleshova Е.S., Sinyukov S.А. et al. Kliniko-elektroentsefalograficheskaya kharakteristika deystviya noopepta u bol’nykh s legkimi kognitivnymi rassroystvami posttravmaticheskogo I sosudistogo geneza [Clinical and electroencephalographic characteristic of noopept in patients with mild cognitive impairment of posttraumatic and vascular origin]. Zh Nevrol Psikhiatr Im S S Korsakova 2008; 108(11): 47-54. PMID: 19008801. (In Russ.)
  69. Vakhitova Y.V., Sadovnikov S.V., Borisevich S.S. et al. Molecular mechanism underlying the action of substituted Pro-Gly Dipeptide Noopept. Acta Naturae 2016; 8(1): 82-89. PMID: 27099787.
  70. Kondratenko R.V., Derevyagin V.I., Skrebitsky V.G. Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells. Neurosci Lett 2010; 476(2): 70-73. doi: 10.1016/j.neulet.2010.04.005. PMID: 20382202.
  71. Колбаев С.Н., Александрова О.П., Шаронова И.Н., Скребицкий В.Г. Vliyanie noopepta na dinamiku [Ca2+]i v neyronakh kul’tiviruemukh srezov gippokampa krysy [Effect of Noopept on dynamics of intracellular calcium in neurons of cultured rat hippocampal slices]. Bull Exp Biol Med 2018; 164(3): 330- 333. doi: 10.1007/s10517-018-3983-3. PMID: 29313229.

Supplementary files

Supplementary Files

Copyright (c) 2018 Skrebitsky V.G., Sharonova I.N.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies