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Neuroscience Bulletin

, Volume 34, Issue 6, pp 1007–1016 | Cite as

GABAA Receptor Activity Suppresses the Transition from Inter-ictal to Ictal Epileptiform Discharges in Juvenile Mouse Hippocampus

  • Yan-Yan Chang
  • Xin-Wei Gong
  • Hai-Qing Gong
  • Pei-Ji Liang
  • Pu-Ming ZhangEmail author
  • Qin-Chi LuEmail author
Original Article
  • 119 Downloads

Abstract

Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABAA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg2+-free artificial cerebrospinal fluid (ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg2+-free ACSF for 10 min–20 min, synchronous recurrent seizure-like events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges (IIDs) to pre-ictal epileptiform discharges (PIDs), and then to IDs. During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 μmol/L of the GABAA receptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 μmol/L muscimol abolished all the epileptiform discharges. When the GABAA receptor antagonist bicuculline was applied at 10 μmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABAA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.

Keywords

Epileptiform discharge Gamma-aminobutyric acid Bicuculline Muscimol Micro-electrode array Hippocampal slice 

Notes

Acknowledgements

This work was supported by the Key Basic Research Project of Science and Technology Commission of Shanghai (13DJ1400303), the Shanghai Jiao Tong University Fund for Interdisciplinary Research for Medical Applications (YG2012ZD08), and the Seed Fund of Ren Ji Hospital (RJ ZZ13-005).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Tatum WOt. Mesial temporal lobe epilepsy. J Clin Neurophysiol 2012, 29: 356–365.Google Scholar
  2. 2.
    Weinand ME, Carter LP, el-Saadany WF, Sioutos PJ, Labiner DM, Oommen KJ. Cerebral blood flow and temporal lobe epileptogenicity. J Neurosurg 1997, 86: 226–232.Google Scholar
  3. 3.
    Litt B, Lehnertz K. Seizure prediction and the preseizure period. Curr Opin Neurol 2002, 15: 173–177.CrossRefGoogle Scholar
  4. 4.
    Dzhala VI, Staley KJ. Transition from interictal to ictal activity in limbic networks in vitro. J Neurosci 2003, 23: 7873–7880.CrossRefGoogle Scholar
  5. 5.
    Zhang ZJ, Valiante TA, Carlen PL. Transition to seizure: from “macro”- to “micro”-mysteries. Epilepsy Res 2011, 97: 290–299.CrossRefGoogle Scholar
  6. 6.
    Baumgartner C, Serles W, Leutmezer F, Pataraia E, Aull S, Czech T, et al. Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset. J Nucl Med 1998, 39: 978–982.PubMedGoogle Scholar
  7. 7.
    Holmes GL. Epilepsy in the developing brain: lessons from the laboratory and clinic. Epilepsia 1997, 38: 12–30.CrossRefGoogle Scholar
  8. 8.
    Tyzio R, Holmes GL, Ben-Ari Y, Khazipov R. Timing of the developmental switch in GABA(A) mediated signaling from excitation to inhibition in CA3 rat hippocampus using gramicidin perforated patch and extracellular recordings. Epilepsia 2007, 48 Suppl 5: 96–105.CrossRefGoogle Scholar
  9. 9.
    Dzhala VI, Staley KJ. Excitatory actions of endogenously released GABA contribute to initiation of ictal epileptiform activity in the developing hippocampus. J Neurosci 2003, 23: 1840–1846.CrossRefGoogle Scholar
  10. 10.
    Dzhala VI, Talos DM, Sdrulla DA, Brumback AC, Mathews GC, Benke TA, et al. NKCC1 transporter facilitates seizures in the developing brain. Nat Med 2005, 11: 1205–1213.CrossRefGoogle Scholar
  11. 11.
    Lasztoczi B, Nyitrai G, Heja L, Kardos J. Synchronization of GABAergic inputs to CA3 pyramidal cells precedes seizure-like event onset in juvenile rat hippocampal slices. J Neurophysiol 2009, 102: 2538–2553.CrossRefGoogle Scholar
  12. 12.
    Derchansky M, Jahromi SS, Mamani M, Shin DS, Sik A, Carlen PL. Transition to seizures in the isolated immature mouse hippocampus: a switch from dominant phasic inhibition to dominant phasic excitation. J Physiol 2008, 586: 477–494.CrossRefGoogle Scholar
  13. 13.
    Gonzalez-Sulser A, Wang J, Motamedi GK, Avoli M, Vicini S, Dzakpasu R. The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array. Neuropharmacology 2011, 60: 1142–1153.CrossRefGoogle Scholar
  14. 14.
    Liu JS, Li JB, Gong XW, Gong HQ, Zhang PM, Liang PJ, et al. Spatiotemporal dynamics of high-K+-induced epileptiform discharges in hippocampal slice and the effects of valproate. Neurosci Bull 2013, 29: 28–36.CrossRefGoogle Scholar
  15. 15.
    Gong XW, Yang F, Liu JS, Lu QC, Gong HQ, Liang PJ, et al. Investigation of the initiation site and propagation of epileptiform discharges in hippocampal slices using microelectrode array. Prog Biochem Biophys 2011, 37: 1240–1247.CrossRefGoogle Scholar
  16. 16.
    Gonzalez-Sulser A, Wang J, Queenan BN, Avoli M, Vicini S, Dzakpasu R. Hippocampal neuron firing and local field potentials in the in vitro 4-aminopyridine epilepsy model. J Neurophysiol 2012, 108: 2568–2580.CrossRefGoogle Scholar
  17. 17.
    de la Prida LM, Huberfeld G, Cohen I, Miles R. Threshold behavior in the initiation of hippocampal population bursts. Neuron 2006, 49: 131–142.CrossRefGoogle Scholar
  18. 18.
    McCormick DA, Contreras D. On the cellular and network bases of epileptic seizures. Annu Rev Physiol 2001, 63: 815–846.CrossRefGoogle Scholar
  19. 19.
    Shi YJ, Gong XW, Gong HQ, Liang PJ, Zhang PM, Lu QC. Effect of the entorhinal cortex on ictal discharges in low-Mg2+ -induced epileptic hippocampal slice models. Neural Plasticity 2014, 2014: 1–15.CrossRefGoogle Scholar
  20. 20.
    Zhang ZJ, Koifman J, Shin DS, Ye H, Florez CM, Zhang L, et al. Transition to seizure: ictal discharge is preceded by exhausted presynaptic GABA release in the hippocampal CA3 region. J Neurosci 2012, 32: 2499–2512.CrossRefGoogle Scholar
  21. 21.
    Rajna P, Clemens B, Csibri E, Dobos E, Geregely A, Gottschal M, et al. Hungarian multicentre epidemiologic study of the warning and initial symptoms (prodrome, aura) of epileptic seizures. Seizure 1997, 6: 361–368.CrossRefGoogle Scholar
  22. 22.
    Slone E, Westwood E, Dhaliwal H, Federico P, Dunn JF. Near-infrared spectroscopy shows preictal haemodynamic changes in temporal lobe epilepsy. Epileptic Disord 2012, 14: 371–378.PubMedGoogle Scholar
  23. 23.
    Navarro V, Martinerie J, Le Van Quyen M, Clemenceau S, Adam C, Baulac M, et al. Seizure anticipation in human neocortical partial epilepsy. Brain 2002, 125: 640–655.CrossRefGoogle Scholar
  24. 24.
    Li JJ, Li YH, Gong HQ, Liang PJ, Zhang PM, Lu QC. The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice. PLoS One 2016, 11: e0153897.CrossRefGoogle Scholar
  25. 25.
    Jin B, So NK, Wang S. Advances of intracranial electroencephalography in localizing the epileptogenic zone. Neurosci Bull 2016, 32: 493–500.CrossRefGoogle Scholar
  26. 26.
    Wittner L, Miles R. Factors defining a pacemaker region for synchrony in the hippocampus. J Physiol 2007, 584: 867–883.CrossRefGoogle Scholar
  27. 27.
    Li XG, Somogyi P, Ylinen A, Buzsaki G. The hippocampal CA3 network: an in vivo intracellular labeling study. J Comp Neurol 1994, 339: 181–208.CrossRefGoogle Scholar
  28. 28.
    Weissinger F, Buchheim K, Siegmund H, Heinemann U, Meierkord H. Optical imaging reveals characteristic seizure onsets, spread patterns, and propagation velocities in hippocampal-entorhinal cortex slices of juvenile rats. Neurobiol Dis 2000, 7: 286–298.CrossRefGoogle Scholar
  29. 29.
    Avoli M, de Curtis M. GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity. Prog Neurobiol 2011, 95: 104–132.CrossRefGoogle Scholar
  30. 30.
    Khazipov R, Khalilov I, Tyzio R, Morozova E, Ben-Ari Y, Holmes GL. Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus. Eur J Neurosci 2004, 19: 590–600.CrossRefGoogle Scholar
  31. 31.
    Fujiwara-Tsukamoto Y, Isomura Y, Nambu A, Takada M. Excitatory gaba input directly drives seizure-like rhythmic synchronization in mature hippocampal CA1 pyramidal cells. Neuroscience 2003, 119: 265–275.CrossRefGoogle Scholar
  32. 32.
    Staley K, Smith R, Schaack J, Wilcox C, Jentsch TJ. Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel. Neuron 1996, 17: 543–551.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Neurology, Ren Ji Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  2. 2.School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina

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