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Inhibition of spontaneous synchronous activity of hippocampal neurons by excitation of GABAergic neurons

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

Abstract

The molecular mechanisms of the neuronal spontaneous synchronous activity (SSA) regulation by population of GABAergic neurons have been investigated in rat hippocampal culture. The neurons from this population contain Ca2+-permeable KA receptors on the presynaptic membrane. Using image analysis, confocal microscopy and immunocytochemistry, we identified by the shape of Ca2+ signal the population of GABAergic neurons with unique charachteristics allowing these neurons to control SSA. The SSA in a neuronal network was suppressed by the KA-receptor mediated [Ca2+]i increase in neurons of this population. Agonists of GluR5/GluK1-containing KA receptors (domoic acid (DA), SYM2081, and ATPA) evoked a fast high-amplitude Ca2+ signal without desensitization only in this population of neurons. This fact points to Ca2+ permeability of KA receptors in these neurons. The GABA(A) receptor antagonist bicuculline increased the activity of AMPA but not KA receptors of these neurons, indicating presynaptical localization of KA receptors. Depolarization of cells induced by KCl (unlike bicuculline-induced depolarization) increased the activity of AMPA and KA receptors twofold, which points to the dependence of the activity on depolarization. A tenfold increase of the SSA frequency in neurons of this population caused an increase in the basal [Ca2+]i level, which was accompanied by inhibition of SSA in another numerous population of neurons, suggesting that an increased GABAergic inhibition takes place. Prolonged high-frequency oscillations causes a global [Ca2+]i increase in the neurons of this population and their subsequent death. Thus, KA receptors in the population of fast GABAergic neurons may implement a negative feedback under hyperexcitation by glutamate enhancing GABA release due to the fast and prolonged [Ca2+]i increase. It has been shown that this mechanism can be used to suppress hyperactivation of a certain population of neurons under high-frequency SSA and ischemia. It is obvious that selective death of inhibitory neurons from this population may lead to hyperexcitability of certain brain regions.

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Abbreviations

AMPA:

a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

[Ca2+] i :

concentration of free cytosolic calcium

cAMP:

cyclic adenosine monophosphate

GABA:

γ-aminobutyric acid

GluR:

glutamate receptor

IL:

interleukin

KA:

kainate

NMDA:

N-methyl-D-aspartate

DIV:

days in vitro

FW:

fluorowillardiine

GYKI:

a selective AMPA receptor antagonist GYKI 52466

DA:

domoic acid

GAD 65/67:

glutamate decarboxylase 65/67

References

  1. Bacci A., Verderio C., Pravettoni E., Matteoli M. 1999. Synaptic and intrinsic mechanisms shape synchronous oscillations in hippocampal neurons in culture. Eur. J. Neurosci. 11(2), 389–397.

    Article  CAS  PubMed  Google Scholar 

  2. Rosay P., Armstrong J.D., Wang Z., Kaiser K. 2001. Synchronized neural activity in the Drosophila memory centers and its modulation by amnesiac. Neuron. 30(3), 759–770.

    Article  CAS  PubMed  Google Scholar 

  3. Timofeev I. 2011. Neuronal plasticity and thalamocortical sleep and waking oscillations. Prog. Brain Res. 193, 121–144.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kuijlaars J., Oyelami T., Diels A., Rohrbacher J., Versweyveld S., Meneghello G., Tuefferd M., Verstraelen P., Detrez J.R., Verschuuren M., De Vos W.H., Meert T., Peeters P.J., Cik M., Nuydens R., Brone B., Verheyen A. 2016. Sustained synchronized neuronal network activity in a human astrocyte co-culture system. Sci. Rep. 6, 36529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang X., Gruenstein E.I. 1997. Mechanism of synchronized Ca2+ oscillations in cortical neurons. Brain Res. 767(2), 239–249.

    Article  CAS  PubMed  Google Scholar 

  6. Dolmetsch R.E., Xu K., Lewis R.S. 1998. Calcium oscillations increase the efficiency and specificity of gene expression. Nature. 392(6679), 933–936.

    Article  CAS  PubMed  Google Scholar 

  7. Ogura A., Iijima T., Amano T., Kudo Y. 1987. Optical monitoring of excitatory synaptic activity between cultured hippocampal neurons by a multi-site Ca2+ fluorometry. Neurosci. Lett. 78(1), 69–74.

    Article  CAS  PubMed  Google Scholar 

  8. Tanaka T., Saito H., Matsuki N. 1996. Intracellular calcium oscillation in cultured rat hippocampal neurons: A model for glutamatergic neurotransmission. Jpn. J. Pharmacol. 70(1), 89–93.

    Article  CAS  PubMed  Google Scholar 

  9. Spitzer N.C., Olson E.X. 1995. Spontaneous calcium transients regulate neuronal plasticity in developing neurons. J. Neurobiol. 26(3), 316–324.

    Article  CAS  PubMed  Google Scholar 

  10. Li W., Llopis J., Whitney M., Zlokarnik G., Tsien R.Y. 1998. Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature. 392(6679), 936–941.

    Article  CAS  PubMed  Google Scholar 

  11. Contractor A., Swanson G.T., Sailer A., O’Gorman S., Heinemann S.F. 2000. Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. J. Neurosci. 20(22), 8269–8278.

    CAS  PubMed  Google Scholar 

  12. Schmitz D., Frerking M., Nicoll R.A. 2000. Synaptic activation of presynaptic kainate receptors on hippocampal mossy fiber synapses. Neuron. 27(2), 327–338.

    Article  CAS  PubMed  Google Scholar 

  13. Rodrıguez-Moreno A., Lerma J. 1998. Kainate receptor modulation of GABA release involves a metabotropic function. Neuron. 20(6), 1211–1218.

    Article  PubMed  Google Scholar 

  14. Kononov A.V., Bal’ N.V., Zinchenko V.P. 2012. Control of spontaneous synchronous Ca2+ oscillations in hippocampal neurons by GABAergic neurons containing kainate receptors without desensitization. Biol. Membrany (Rus.). 29(1), 133–138.

    CAS  Google Scholar 

  15. Turovskaya M.V., Turovsky E.A., Kononov A.V., Zinchenko V.P. 2013. Short-term hypoxia induces a selective death of GABAergic neurons. Biol. Membrany (Rus.). 30(5–6), 479–490.

    CAS  Google Scholar 

  16. Dynnik V.V., Kononov A.V., Sergeev A.V., Tankanag A., Zinchenko V.P. 2015. To break or not to brake neuronal network accelerated by ammonium ions? PLoS One. 10(7): e0134145.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cobb S.R., Buhl E.H., Halasy K., Paulsen O., Somogyi P. 1995. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature. 378(6552), 75–78.

    Article  CAS  PubMed  Google Scholar 

  18. Lerma J. 2003. Roles and rules of kainate receptors in synaptic transmission. Nat. Rev. Neurosci. 4(6), 481–495.

    Article  CAS  PubMed  Google Scholar 

  19. Mann E.O., Paulsen O. 2007. Role of GABAergic inhibition in hippocampal network oscillations. Trends Neurosci. 30(7), 343–349.

    Article  CAS  PubMed  Google Scholar 

  20. Berezhnov A.V, Kononov A.V., Fedotova E.I., Zinchenko V.P. 2011. A method for the detection and characterization of GABA(A) receptors by calciumsensitive fluorescent probes. Biofizika (Rus.). 56(4), 673–683.

    CAS  Google Scholar 

  21. Berezhnov A.V., Kononov A.V., Fedotova E.I., Zinchenko V.P. 2013. Image analysis application for ionotropic glutamate receptor ligands characterization in cultured neurons. Biol. Membrany (Rus.). 30(3), 179–188.

    CAS  Google Scholar 

  22. Zinchenko V.P., Turovskaya M.V., Teplov I.Y., Berezhnov A.V., Turovsky E.A. 2016. A role of parvalbumincontaining interneurons in regulation of spontaneous synchronous activity of the brain neurons in culture. Biofizika (Rus.). 61(1), 102–111.

    Google Scholar 

  23. Nishizawa Y. 2001. Glutamate release and neuronal damage in ischemia. Life Sci. 69(4), 369–381.

    Article  CAS  PubMed  Google Scholar 

  24. Hamberger A., Butcher S.P., Hagberg H., Jacobson I., Lehmann A., Sandberg M. 1986. Extracellular concentration of excitatory amino acids: Effects of hyperexcitation, hypoglycemia and ischemia. In: Excitatory amino acids. Eds: Roberts P., Storm-Mathisen J., Bradford H. Palgrave Macmillan UK, p. 409–422.

    Chapter  Google Scholar 

  25. Salińska E., Danysz W., Łazarewicz J. 2005. The role of excitotoxicity in neurodegeneration. Folia Neuropathol. 43(4), 322–339.

    PubMed  Google Scholar 

  26. Zinchenko V.P., Turovsky E.A., Turovskaya M.V., Berezhnov A.V., Sergeev A.I., Dynnik V.V. 2016. NAD causes dissociation of neural networks into subpopulations of neurons by inhibiting the network synchronous hyperactivity evoked by ammonium ions. Biol. Membrany (Rus.). 33(2), 150–158.

    CAS  Google Scholar 

  27. Turovsky E.A., Turovskaya M.V., Gaidin S.G., Zinchenko V.P. 2017. Cytokine IL-10, activators of PI3- kinase, agonists of α-2 adrenoreceptor and antioxidants prevent ischemia-induced cell death in rat hippocampal cultures. Arch. Biochem. Biophys. 615, 35–43.

    Article  CAS  PubMed  Google Scholar 

  28. Gorbunova Y.V., Spitzer N.C. 2002. Dynamic interactions of cyclic AMP transients and spontaneous Ca2+ spikes. Nature. 418(6893), 93–96.

    Article  CAS  PubMed  Google Scholar 

  29. Verkhratsky A., Parpura V., Rodriguez J. 2011. Where the thoughts dwell: The physiology of neuronal-glial “diffuse neural net”. Brain Res. 66(1–2), 133–151.

    Article  Google Scholar 

  30. Koizumi S., Inoue K. 1997. Inhibition by ATP of calcium oscillations in rat cultured hippocampal neurones. Br. J. Pharmacol. 122(1), 51–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bowser D.N., Khakh B.S. 2004. ATP excites interneurons and astrocytes to increase synaptic inhibition in neuronal networks. J. Neurosci. 24(39), 8606–8620.

    Article  CAS  PubMed  Google Scholar 

  32. Kawamura M., Gachet C., Inoue K., Kato F. 2004. Direct excitation of inhibitory interneurons by extracellular ATP mediated by P2Y1 receptors in the hippocampal slice. J. Neurosci. 24(48), 10835–10845.

    Article  CAS  PubMed  Google Scholar 

  33. Gilsbach R., Hein L. 2012. Are the pharmacology and physiology of α2- adrenoceptors determined by α2- heteroreceptors and autoreceptors respectively? Brit. J. Pharmacol. 165(1), 90–102.

    CAS  Google Scholar 

  34. Uchida T., Furukawa T., Iwata S., Yanagawa Y., Fukuda A. 2014. Selective loss of parvalbumin-positive GABAergic interneurons in the cerebral cortex of maternally stressed Gad1-heterozygous mouse offspring. Transl. Psychiatry. 4, e371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cobb S.R., Buhl E.H., Halasy K., Paulsen O., Somogyi P. 1995. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature. 378(6552), 75–78.

    Article  CAS  PubMed  Google Scholar 

  36. Shetty A.K., Hattiangady B., Rao M.S. 2009. Vulnerability of hippocampal GABA-ergic interneurons to kainate- induced excitotoxic injury during old age. J. Cell. Mol. Medicine. 13(8B), 2408–2423.

    Article  Google Scholar 

  37. Franck J.E., Kunkel D.D., Baskin D.G., Schwartzkroin P.A. 1988. Inhibition in kainite-lesioned hyperexcitable hippocampi: Physiologic, autoradiographic, and immunocytochemical observations. J. Neurosci. 8, 1991–2002.

    CAS  PubMed  Google Scholar 

  38. Ben-Ari Y., Cossart R. 2000. Kainate, a double agent that generates seizures: Two decades of progress. Trends Neurosci. 23(11), 580–587.

    Article  CAS  PubMed  Google Scholar 

  39. Sun H.Y., Bartley A.F., Dobrunz L.E. 2009. Calciumpermeable presynaptic kainate receptors involved in excitatory short-term facilitation onto somatostatin interneurons during natural stimulus patterns. J. Neurophysiol. 101(2), 1043–1055.

    Article  CAS  PubMed  Google Scholar 

  40. Schmitz D., Mellor J., Frerking M., Nicoll R. 2001. Presynaptic kainate receptors at hippocampal mossy fiber synapses. Proc. Natl. Acad. Sci. USA. 98(20), 11003–11008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Juuri J., Clarke V., Lauri S.E., Taira T. 2010. Kainate receptor-induced ectopic spiking of CA3 pyramidal neurons initiates network bursts in neonatal hippocampus. J. Neurophysiol. 104(3), 1696–1706.

    Article  CAS  PubMed  Google Scholar 

  42. Clarke V.R.J., Ballyk B.A., Hoo K.H., Mandelzys A., Pellizzari A., Bath C.P., Thomas J., Sharpe E.F., Davies C.H., Ornstein P.L., Schoepp D.D., Kamboj R.K., Collingridge G.L., Lodge D., Bleakman D. 1997. A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission. Nature. 389(6651), 599–603.

    Article  CAS  PubMed  Google Scholar 

  43. Cossart R., Esclapez M., Hirsch J.C., Bernard C., Ben- Ari Y. 1998. GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells. Nat. Neurosci. 1(6), 470–478.

    Article  CAS  PubMed  Google Scholar 

  44. Frerking M., Malenka R.C, Nicoll R.A. 1998. Synaptic activation of kainate receptors on hippocampal interneurons. Nat. Neurosci. 1(6), 479–486.

    Article  CAS  PubMed  Google Scholar 

  45. Frerking M., Petersen C.C., Nicoll R.A. 1999. Mechanisms underlying kainate receptor-mediated disinhibition in the hippocampus. Proc. Natl Acad. Sci. USA. 96(22), 12917–12922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Xu J., Liu Y., Zhang G.Y. 2008. Neuroprotection of GluR5-containing kainate receptor activation against ischemic brain injury through decreasing tyrosine phosphorylation of N-methyl-D-aspartate receptors mediated by Src kinase. J. Biol. Chem. 283(43), 29355–29366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Franke H., Verkhratsky A., Burnstock G., Illes P. 2012. Pathophysiology of astroglial purinergic signalling. Purinergic Signal. 8(3), 629–657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ouyang Y., Xu L., Yue S., Liu S., Giffard R.G. 2014. Neuroprotection by astrocytes in brain ischemia: Importance of microRNAs. Neurosci. Lett. 565, 53–58.

    Article  CAS  PubMed  Google Scholar 

  49. Carmichael S.T. 2012. Brain excitability in stroke: The Yin and Yang of stroke progression. Arch. Neurology. 69(2), 161–167.

    Article  Google Scholar 

  50. Contractor A., Swanson G.T., Sailer A., O’Gorman S., Heinemann S.F. 2000. Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. J. Neurosci. 20(22), 8269–8278.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290, Russia

    V. P. Zinchenko, S. G. Gaidin, I. Y. Teplov & A. M. Kosenkov

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  1. V. P. Zinchenko
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  2. S. G. Gaidin
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  3. I. Y. Teplov
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  4. A. M. Kosenkov
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Correspondence to V. P. Zinchenko.

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Original Russian Text © V.P. Zinchenko, S.G. Gaidin, I.Y. Teplov, A.M. Kosenkov, 2017, published in Biologicheskie Membrany, 2017, Vol. 34, No. 4, pp. 284–297.

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Zinchenko, V.P., Gaidin, S.G., Teplov, I.Y. et al. Inhibition of spontaneous synchronous activity of hippocampal neurons by excitation of GABAergic neurons. Biochem. Moscow Suppl. Ser. A 11, 261–274 (2017). https://doi.org/10.1134/S1990747817040110

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  • DOI: https://doi.org/10.1134/S1990747817040110

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