Skip to main content
SpringerLink
Log in

Synaptic mechanisms of use-dependent potentiation and use-dependent inhibition of evoked burst discharges in rat hippocampal slices

  • Published:
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

The mechanisms of activity-dependent modulation of burst discharges in rat hippocampal slices have been studied. The extracellular registration of field responses (population spike, PS, and field excitatory postsynaptic potential, fEPSP) induced by repetitive electrical stimulation (1–4 Hz) of Schaffer collaterals (with 30 pulses trains separated by 5-min resting intervals) was performed in cellular and dendritic layers of CA1 area. It has been established that repetitive orthodromic stimulation exerts biphasic modulation of burst discharges in Mg2+-free medium: use-dependent potentiation (UDP) and use-dependent inhibition (UDI). The former was manifested as an increase in the number of PS in the burst discharge associated with a corresponding lengthening of the fEPSP. During the UDI development the number of NMDA-dependent PS in the burst was diminished despite the continuing increase in the fEPSP duration. In some cases UDI was followed by spreading depression. Both UDP and UDI were reversible. The development of UDP and UDI could be effectively suppressed either by the NMDA antagonists or by the GABAergic inhibition enhancer, diazepam. The picrotoxin (PTX)-induced burst discharges did not undergo either UDP or UDI development. However, removal of Mg2+ from PTX-containing solution during continuing repetitive stimulation led to the appearance of NMDA-dependent UDI. Analysis of the data obtained indicates that: (1) UDP results from a progressive decrease in GABA-mediated inhibition in the course of low-frequency (1–4 Hz) repetitive stimulation (the so-called “fatigue of synaptic inhibition”); (2) UDI is caused by excessive Ca2+ influx into the neurons due to overactivation of NMDA receptors.

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

Access this article

Log in via an institution

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

Abbreviations

PS:

population spike

fEPSP:

field excitatory postsynaptic potential

UDP:

use-dependent potentiation

UDI:

use-dependent inhibition

SD:

spreading depression

PTX:

picrotoxin

DZ:

diazepam

References

  1. Anderson, W.W., Lewis, D.V., Schwartzwelder, H.S., and Wilson, W.A., Magnesium-Free Medium Activates Seizure-Like Events in the Rat Hippocampal Slice, Brain Res., 1986, vol. 398, pp. 215–219.

    Article  PubMed  CAS  Google Scholar 

  2. Mody, I., Lambert, J.D.C., and Heinemann, U., Low Extracellular Magnesium Induces Epileptiform Activity and Spreading Depression in Rat Hippocampal Slices, J. Neurophysiol., 1987, vol. 57, pp. 869–888.

    PubMed  CAS  Google Scholar 

  3. Tancredi, V., Hwa, G.G., Zona, C., Brancati, A., and Avoli, M., Low Magnesium Epileptogenesis in the Rat Hippocampal Slice: Electrophysiological and Pharmacological Features, Brain Res., 1990, vol. 511, pp. 280–290.

    Article  PubMed  CAS  Google Scholar 

  4. Zhang, C.L., Dreier, J.P., and Heinemann, U., Paroxysmal Epileptiform Discharges in Temporal Lobe Slices after Prolonged Exposure to Low Magnesium are Resistant to Clinically Used Anticonvulsants, Epilepsy Res., 1995, vol. 20, pp. 105–111.

    Article  PubMed  CAS  Google Scholar 

  5. Herron, C.E., Lester, R.A.J., Coan, E.J., and Collingridge, G.L., Frequency Dependent Involvement of NMDA Receptors in the Hippocampus: a Novel Synaptic Mechanism, Nature, 1986, vol. 322, pp. 265–268.

    Article  PubMed  CAS  Google Scholar 

  6. Dreier, J. and Heinemann, U., Regional and Time Dependent Variations of Low Mg2+-Induced Epileptiform Activity in Rat Temporal Cortex Slices, Exp. Brain Res., 1991, vol. 87, P. 581–596.

    Article  PubMed  CAS  Google Scholar 

  7. Marder, C.P. and Buonomano, D.V., Differential Effects of Short- and Long-Term Potentiation on Cell Firing in the CA1 Region of the Hippocampus, J. Neurosci., 2003, vol. 23, no. 1, pp. 112–121.

    PubMed  CAS  Google Scholar 

  8. Albensi, B.C., Ata, G., Schmidt, E., Waterman, J.D., and Janigro, D., Activation of Long-Term Synaptic Plasticity Causes Suppression of Epileptiform Activity in Rat Hippocampal Slices, Brain Res., 2004, vol. 998, pp. 56–64.

    Article  PubMed  CAS  Google Scholar 

  9. Kuncler, P.E. and Kraig, R.P., P/Q Ca2+ Channels Blockade Stops Spreading Depression and Related Pyramidal Neuronal Ca2+ Rise in Hippocampal Organ Culture, Hippocampus, 2004, vol. 14, pp. 356–367.

    Article  Google Scholar 

  10. Kalashnikova, N.V., Motin, V.G., and Khodorov, B.I., Contribution of AMPA- and NMDA-Receptors to Use-Dependent Potentiation and Inhibition of Experimentally-Evoked Epileptiform Activity in Rat Hippocampal Slices, Biol. Membranes, 2005, vol. 1, no. 1, pp. 104–108.

    Google Scholar 

  11. Stanton, P.K., Jones, R.S.G., Mody, I., and Heinemann, U., Epileptiform Activity Induced by Lowering Extracellular [Mg2+] in Combined Hippocampal-Entorhinal Cortex Slices: Modulation by Receptors for Norepinefrine and N-Methyl-D-Aspartate, Epilepsy Res., 1987, vol. 1, pp. 53–62.

    Article  PubMed  CAS  Google Scholar 

  12. Heinemann, U., Lux, H.D., and Gutnick, M.J., Extracellular Free Calcium and Potassium During Paroxysmal Activity in the Cerebral Cortex of the Cat, Exp. Brain Res., 1977, vol. 27, pp. 237–243.

    Article  PubMed  CAS  Google Scholar 

  13. Marciani, M.G., Louvel, J., and Heinemann, U., Aspartate-Induced Changes in Extracellular Free Calcium in “in vitro” Hippocampal Slices of Rats, Brain Res., 1982, vol. 238, pp. 272–277.

    Article  PubMed  CAS  Google Scholar 

  14. Lüthi, A., van der Putten, H., Botteri, F.M., Mansuy, I.M., Meins, M., Frey, U., Sansing, G., Portet, C., Schmutz, M., Schröder, M., Nitsch, C., Laurent, J.-P., and Monard, D., Endogenous Serine Protease Inhibitor Modulates Epileptic Activity and Hippocampal Long-Term Potentiation, J. Neurosci., 1997, vol. 17, no. 12, pp. 4688–4699.

    PubMed  Google Scholar 

  15. Burdette, L.J. and Masukawa, L.M., Stimulus Parameters Affecting Paired-Pulse Depression of Dentate Granule Cell Field Potentials. II. Low-Frequency Stimulation, Brain Res., 1995, vol. 680, nos. 1, 2, pp. 63–72.

    Article  PubMed  CAS  Google Scholar 

  16. Lambert, J.D., Jones, R.S., Andreasen, M., Jensen, M.S., and Heinemann, U., The Role of Excitatory Amino Acids in Synaptic Transmission in the Hippocampus, Comp. Biochem. Physiol., 1989, vol. 93, no. 1, pp. 195–201.

    Article  CAS  Google Scholar 

  17. Anderson, W.W., Epileptogenesis, in Cortical Plasticity, Fazeli, M.S. and Collingridge, G.L., Ed., Oxford: BIOS Scientific Publishers Ltd, 1996, pp. 149–189.

    Google Scholar 

  18. Köhling, R., Gladwell, S.J., Bracci, E., Vreugdenhil, M., and Jefferys, J.G., Prolonged Epileptiform Bursting Induced by 0 Mg2+ in Rat Hippocampal Slices Depends on Gap Junctional Coupling, Neuroscience, 2001, vol. 105, no. 3, pp. 579–587.

    Article  PubMed  Google Scholar 

  19. Basarsky, T.A., Duffy, S.N., Andrew, R.D., and MacVicar, B.A., Imaging Spreading Depression and Associated Intracellular Calcium Waves in Brain Slices, J. Neurosci., 1998, vol. 18, no. 18, pp. 7189–7199.

    PubMed  CAS  Google Scholar 

  20. Somjen, G.G., Mechanisms of Spreading Depression and Hypoxic Spreading Depression-Like Depolarization, Physiol. Rev., 2001, vol. 81, no. 3, pp. 1065–1096.

    PubMed  CAS  Google Scholar 

  21. Somjen, G.G., Is Spreading Depression Bad for You? Focus on “Repetitive Normoxic Spreading Depression-Like Events Result in Cell Damage in Juvenile Hippocampal Slice Cultures,” J. Neurophysiol., 2006, vol. 95, pp. 16–17.

    Article  PubMed  Google Scholar 

  22. Twyman, R.E., Rogers, C.J., and Macdonald, R.L., Differential Regulation of Gamma-Aminobutyric Acid Receptor Channels by Diazepam and Phenobarbital, Ann. Neurol., 1989, vol. 25, no. 3, pp. 213–220.

    Article  PubMed  CAS  Google Scholar 

  23. File, S.E., Mabbutt, P.S., and Andrews, N., Diazepam Withdrawal Responses Measured in the Social Interaction Test of Anxiety and Their Reversal by Baclofen, Psychopharmacol., 1991, vol. 104, pp. 62–66.

    Article  CAS  Google Scholar 

  24. Korpi, E.R., Grunder, G., and Luddens, H., Drug Interactions at GABA(A) Receptors, Prog. Neurobiol., 2002, vol. 67, pp. 113–159.

    Article  PubMed  CAS  Google Scholar 

  25. Moncada, S., Palmer, R.M.J., and Higgs, E.A., Nitric Oxide: Physiology, Pathophysiology and Pharmacology, Pharmacol. Rev., 1991, vol. 43, pp. 109–141.

    PubMed  CAS  Google Scholar 

  26. Dawson, T.M., Zhang, J., Dawson, V.L., and Snyder, S.H., Nitric Oxide: Cellular Regulation and Neuronal Injury, Prog. Brain Res., 1994, vol. 103, pp. 365–369.

    Article  PubMed  CAS  Google Scholar 

  27. Jacoby, S., Sims, R.E., and Hartell, N.A., Nitric Oxide is Required for the Induction and Heterosynaptic Spread of Long-Term Potentiation in Rat Cerebellar Slices, J. Physiol., 2001, vol. 535, part 3, pp. 825–839.

    Article  PubMed  CAS  Google Scholar 

  28. Hardingham, N. and Fox, K., The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation, J. Neurosci., 2006, vol. 26, no. 28, pp. 7395–7404.

    Article  PubMed  CAS  Google Scholar 

  29. Raevsky K.S., Nitric oxide, a New Physiological Messenger: Possible Role in Pathology of Control Nerwous System, Bull. Exp. Biol. Med. (Rus.), 1997, vol. 123, pp. 484–490.

    Google Scholar 

  30. Schuchmann, S., Albrecht, D., Heinemann, U., and von Bohlen und Halbach, O., Nitric Oxide Modulates Low-Mg2+-Induced Epileptiform Activity in Rat Hippocampal-Entorhinal Cortex Slices, Neurobiol. Dis., 2002, vol. 11, pp. 96–105.

    Article  PubMed  CAS  Google Scholar 

  31. Yasuda, H., Fujii, M., Fujisawa, H., Ito, H., and Suzuki, M., Changes in Nitric Oxide Synthesis and Epileptic Activity in the Contralateral Hippocampus of Rats Following Intrahippocampal Kainite Injection, Epilepsia, 2001, vol. 42, pp. 13–20.

    Article  PubMed  CAS  Google Scholar 

  32. Bashkatova, V., Narkevich, V., Vitskova, G., and Vanin, A., The Influence of Anticonvulsant and Antioxidant Drugs on Nitric Oxide Level and Lipid Peroxidation in the Rat Brain During Penthylenetetrazole-Induced Epileptiform Model Seizures, Prog. Neuropsychopharmacol. Biol. Psychiatry, 2003, vol. 27, pp. 487–492.

    Article  PubMed  CAS  Google Scholar 

  33. Penix, L.P., Davis, W., and Subramaniam, S., Inhibition of NO Synthase Increases the Severity of Kainic Acid-Induced Seizures in Rodents, Epilepsy Res., 1994, vol. 18, pp. 177–184.

    Article  PubMed  CAS  Google Scholar 

  34. Przegaliinski, E., Baran, L., and Siwanowicz, J., The Role of Nitric Oxide in Chemically- and Electrically-Induces Seizures in Mice, Neurosci. Lett., 1996, vol. 217, pp. 145–148.

    Google Scholar 

  35. Hablitz, J.J., Picritoxin-Induced Epileptiform Activity in Hippocampus: Role of Endogenous Versus Synaptic Factors, J. Neurophysiol., 1984, vol. 51, pp. 1011–1027.

    PubMed  CAS  Google Scholar 

  36. Fellin, T., Gomez-Gonzalo, M., Gobbo, S., Carmignoto, G., and Haydon, P.G., Astrocytic Glutamate is not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices, J. Neurosci., 2006, vol. 26, no. 36, pp. 9312–9322.

    Article  PubMed  CAS  Google Scholar 

  37. Köhr, G. and Heinemann, U., Effects of NMDA Antagonists on Picrotoxin-, Low Mg2+- and Low Ca2+-Induced Epileptogenesis and on Evoked Changes in Extracellular Na+ and Ca2+ Concentrations in Rat Hippocampal Slices, Epilepsy Res., 1989, vol. 4, pp. 187–200.

    Article  PubMed  Google Scholar 

  38. Goda, M., Kovac, S., Speckmann, E.J., and Gorji, A., Glutamate and Dopamine Receptors Contribute to the Lateral Spread of Epileptiform Discharges in Rat Neocortical Slices, Epilepsia, 2008, vol. 49, no. 2, pp. 237–247.

    Article  PubMed  Google Scholar 

  39. Heinemann, U., Hamon, B., Konnerth, A., and Wadman, W.J., Stimulus-Dependent Synaptic Plasticity in Area CA1 of the in vitro Hippocampal Slice of Rats, Exp. Brain Res., 1986, vol. 14, pp. 291–299.

    Google Scholar 

  40. Hablitz, J.J. and Heinemann, U., Alterations in the Microenvironment During Spreading Depression Associated with Epileptiform Activity in the Immature Neocortex, Brain Res. Dev. Brain Res., 1989, vol. 46, pp. 243–252.

    Article  PubMed  CAS  Google Scholar 

  41. Hoyt, K.R., Tang, L.H., Aizenman, E., and Reynolds, I.J., Nitric Oxide Modulates NMDA-Induced Increases in Intracellular Ca2+ in Cultured Rat Forebrain Neurons, Brain Res., 1992, vol. 592, nos. 1, 2, pp. 310–316.

    Article  PubMed  CAS  Google Scholar 

  42. Davies, C.H., Starkey, S.J., Pozza, M.F., and Collingridge, G.L., The GABA Autoreceptors Regulate the Induction of LTP, Nature, 1991, vol. 349, no. 6310, pp. 609–611.

    Article  PubMed  CAS  Google Scholar 

  43. Brown, J.T., Davies, C.H., and Randall, A.D., Synaptic Activation of GABA(B) Receptors Regulates Neuronal Network Activity and Entrainment, Eur J Neurosci., 2007, vol. 25, no. 10, pp. 2982–2990.

    Article  PubMed  Google Scholar 

  44. Mori, M., Abegg, M.H., Gähwiler, B.H., and Gerber, U., A Frequency-Dependent Switch from Inhibition to Excitation in a Hippocampal Unitary Circuit, Nature, 2004, vol. 431, no. 7007, pp. 453–456.

    Article  PubMed  CAS  Google Scholar 

  45. Mann, E.O. and Paulsen, O., Role of GABAergic Inhibition in Hippocampal Network Oscillations, Trends Neurosci., 2007, vol. 30, no. 7, pp. 343–349.

    Article  PubMed  CAS  Google Scholar 

  46. Thompson, S.M., Capogna, M., and Scanziani, M., Presynaptic Inhibition in the Hippocampus, Trends Neurosci., 1993, vol. 16, pp. 222–227.

    Article  PubMed  CAS  Google Scholar 

  47. Jensen, K., Lambert, J.D.C., and Jensen, M.S., Activity-Dependent Depression of GABAergic IPSCs in Cultured Hippocampal Neurons, J. Neurophysiol., 1999, vol. 82, pp. 42–49.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of General Pathology and Pathophysiology RAMS, Baltiiskaya ul., 8, Moscow, 125315, Russia

    N. V. Kalashnikova, V. G. Motin & B. I. Khodorov

Authors
  1. N. V. Kalashnikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. G. Motin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. I. Khodorov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. I. Khodorov.

Additional information

The article is published in the original.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kalashnikova, N.V., Motin, V.G. & Khodorov, B.I. Synaptic mechanisms of use-dependent potentiation and use-dependent inhibition of evoked burst discharges in rat hippocampal slices. Biochem. Moscow Suppl. Ser. A 3, 206–215 (2009). https://doi.org/10.1134/S1990747809020147

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990747809020147

Key words

Search

Navigation