Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-27T19:07:55.014Z Has data issue: false hasContentIssue false
  • English
  • Français

Kainate receptors and signal integration by NG2 glial cells

Published online by Cambridge University Press:  22 December 2009

Maria Kukley  and
Dirk Dietrich
Maria Kukley
Affiliation:
Department of Neurosurgery, University Clinic Bonn, Bonn, Germany
Dirk Dietrich*
Affiliation:
Department of Neurosurgery, University Clinic Bonn, Bonn, Germany
*
Correspondence should be addressed to: Dirk Dietrich, Department of Neurosurgery, NCH U1 R035, Experimental Neurophysiology University Clinic Bonn, Sigmund-Freud Street 25, D-53105 Bonn, Germany phone: (49) 228 287 1 9224 fax: (49) 228 287 1 1718 email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

It is well established that NG2 cells throughout the young and adult brain consistently detect the release of single vesicles filled with glutamate from nearby axons. The released neurotransmitter glutamate electrically excites NG2 cells via non-NMDA (N-methyl-D-aspartic acid) glutamate receptors but the individual contribution of AMPA and kainate receptors to neuron-NG2 cell signalling, is not well understood. Here we pharmacologically block AMPA-type glutamate receptors and investigate whether hippocampal NG2 cells also express the kainate subtype of glutamate receptors and what may be their contribution to synaptic connectivity. It has been shown previously that vesicular glutamate release does not lead to a detectable activation of kainate receptors on NG2 cells. Here we report that while bath application of 250 nM–1 μM kainate does not have a major effect on NG2 cells it consistently induces a small and persistent depolarising current. This current was not mimicked by ATPA, suggesting that this current is carried by non-GluR5 containing kainate receptors. In addition to this inward current, nanomolar concentrations of kainate also produced a dramatic increase in the frequency of spontaneous GABA-A receptor-mediated synaptic currents (IPSCs) in NG2 cells. This increase in spontaneous IPSC frequency was even more pronounced on application of the GluR5-specific agonist ATPA (approximately 15-fold increase in frequency). In contrast, mono-synaptic stimulated IPSCs recorded in NG2 cells were unaffected by kainate receptor activation. Those and further experiments show that the occurrence of the high frequency of IPSCs is due to action potential firing of hippocampal interneurons caused by activation of GluR5 receptors on the somatodendritic membrane of the interneurons. Our data suggest that hippocampal kainate receptors are not only important for communication between neurons but may also play a dual and subtype-specific role for neuron–glia signalling: Firstly, extra-synaptic non-GluR5 kainate receptors in the membrane of NG2 cells are ideally suited to instruct NG2 cells on the population activity of local excitatory neurons via ambient glutamate. Secondly, based on the known importance of GluR5 receptors on hippocampal interneurons for the generation of network rhythms and based on our finding that these interneurons heavily project onto NG2 cells, it appears that synaptic activation of interneuronal GluR5 receptors triggers signalling to NG2 cells which transmits the phase and frequency of ongoing network oscillations in the developing hippocampus.

Keywords

Neuron–glia synapsesextrasynaptic glutamate receptorshippocampal interneuronsoligodendrocyte precursor cells
Type
Research Article
Information
Neuron Glia Biology , Volume 5 , Special Issue 1-2: NG2-Glia, Part I: NG2 Cells as Components of Neural Circuits , May 2009 , pp. 13 - 20
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Barres, B.A. and Raff, M.C. (1993) Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons. Nature 361, 258–260.CrossRefGoogle ScholarPubMed
Bergles, D.E., Roberts, J.D., Somogyi, P. and Jahr, C.E. (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187–191.CrossRefGoogle ScholarPubMed
Bettler, B. and Mulle, C. (1995) Review: neurotransmitter receptors. II. AMPA and kainate receptors. Neuropharmacology 34, 123–139.CrossRefGoogle ScholarPubMed
Castillo, P.E., Malenka, R.C. and Nicoll, R.A. (1997) Kainate receptors mediate a slow postsynaptic current in hippocampal CA3 neurons. Nature 388, 182–186.CrossRefGoogle ScholarPubMed
Chittajallu, R., Aguirre, A. and Gallo, V. (2004) NG2-positive cells in the mouse white and grey matter display distinct physiological properties. Journal of Physiology 561, 109–122.CrossRefGoogle ScholarPubMed
Cobb, S.R., Buhl, E.H., Halasy, K., Paulsen, O. and Somogyi, P. (1995) Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378, 75–78.CrossRefGoogle ScholarPubMed
Cossart, R., Epsztein, J., Tyzio, R., Becq, H., Hirsch, J., Ben-Ari, Y. et al. (2002) Quantal release of glutamate generates pure kainate and mixed AMPA/kainate EPSCs in hippocampal neurons. Neuron 35, 147–159.CrossRefGoogle ScholarPubMed
Cossart, R., Esclapez, M., Hirsch, J.C., Bernard, C. and Ben-Ari, Y. (1998) GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells. Nature Neuroscience. 1, 470–478.CrossRefGoogle ScholarPubMed
Demerens, C., Stankoff, B., Logak, M., Anglade, P., Allinquant, B., Couraud, F. et al. (1996) Induction of myelination in the central nervous system by electrical activity. Proceedings of the National Academy of Sciences of the U.S.A. 93, 9887–9892.CrossRefGoogle ScholarPubMed
Fields, R.D. (2005) Myelination: an overlooked mechanism of synaptic plasticity?. Neuroscientist 11, 528–531.CrossRefGoogle ScholarPubMed
Frerking, M. and Nicoll, R.A. (2000) Synaptic kainate receptors. Current Opinion in Neurobiology 10, 342–351.CrossRefGoogle ScholarPubMed
Frerking, M. and Ohliger-Frerking, P. (2002) AMPA receptors and kainate receptors encode different features of afferent activity. Journal of Neuroscience 22, 7434–7443.CrossRefGoogle ScholarPubMed
Gallo, V., Mangin, J.M., Kukley, M. and Dietrich, D. (2008) Synapses on NG2-expressing progenitors in the brain: multiple functions?. Journal of Physiology 586, 3767–3781.CrossRefGoogle ScholarPubMed
Gueler, N., Kukley, M. and Dietrich, D. (2007) TBOA-sensitive uptake limits glutamate penetration into brain slices to a few micrometers. Neuroscience Letters 419, 269–272.CrossRefGoogle ScholarPubMed
Huettner, J.E. (2003) Kainate receptors and synaptic transmission. Progress in Neurobiology 70, 387–407.CrossRefGoogle ScholarPubMed
Jane, D.E., Lodge, D. and Collingridge, G.L. (2009) Kainate receptors: pharmacology, function and therapeutic potential. Neuropharmacology 56, 90–113.CrossRefGoogle ScholarPubMed
Karadottir, R., Hamilton, N.B., Bakiri, Y. and Attwell, D. (2008) Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter. Nature Neuroscience 11, 450–456.CrossRefGoogle ScholarPubMed
Kukley, M., Capetillo-Zarate, E. and Dietrich, D. (2007) Vesicular glutamate release from axons in white matter. Nature Neuroscience 10, 311–320.CrossRefGoogle ScholarPubMed
Kukley, M., Kiladze, M., Tognatta, R., Hans, M., Swandulla, D., Schramm, J. et al. (2008) Glial cells are born with synapses. FASEB Journal. 22, 2957–2969.CrossRefGoogle ScholarPubMed
Lahtinen, H., Palva, J.M., Sumanen, S., Voipio, J., Kaila, K. and Taira, T. (2002) Postnatal development of rat hippocampal gamma rhythm in vivo. Journal of Neurophysiology 88, 1469–1474.CrossRefGoogle ScholarPubMed
Lin, S.C. and Bergles, D.E. (2004) Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nature Neuroscience 7, 24–32.CrossRefGoogle ScholarPubMed
Lin, S.C., Huck, J.H., Roberts, J.D., Macklin, W.B., Somogyi, P. and Bergles, D.E. (2005) Climbing fiber innervation of NG2-expressing glia in the mammalian cerebellum. Neuron 46, 773–785.CrossRefGoogle ScholarPubMed
Liu, Q.S., Xu, Q., Arcuino, G., Kang, J. and Nedergaard, M. (2004) Astrocyte-mediated activation of neuronal kainate receptors. Proceedings of the National Academy of Sciences of the U.S.A. 101, 3172–3177.CrossRefGoogle ScholarPubMed
Mangin, J.M., Kunze, A., Chittajallu, R. and Gallo, V. (2008) Satellite NG2 progenitor cells share common glutamatergic inputs with associated interneurons in the mouse dentate gyrus. Journal of Neuroscience 28, 7610–7623.CrossRefGoogle ScholarPubMed
Matthias, K., Kirchhoff, F., Seifert, G., Huttmann, K., Matyash, M., Kettenmann, H. et al. (2003) Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. Journal of Neuroscience 23, 1750–1758.CrossRefGoogle ScholarPubMed
Melyan, Z., Wheal, H.V. and Lancaster, B. (2002) Metabotropic-mediated kainate receptor regulation of IsAHP and excitability in pyramidal cells. Neuron 34, 107–114.CrossRefGoogle ScholarPubMed
Mohns, E.J. and Blumberg, M.S. (2008) Synchronous bursts of neuronal activity in the developing hippocampus: modulation by active sleep and association with emerging gamma and theta rhythms. Journal of Neuroscience 28, 10134–10144.CrossRefGoogle ScholarPubMed
Morin, F., Beaulieu, C. and Lacaille, J.C. (1998) Cell-specific alterations in synaptic properties of hippocampal CA1 interneurons after kainate treatment. Journal of Neurophysiology 80, 2836–2847.CrossRefGoogle ScholarPubMed
Ni, Y., Malarkey, E.B. and Parpura, V. (2007) Vesicular release of glutamate mediates bidirectional signaling between astrocytes and neurons. Journal of Neurochemistry 103, 1273–1284.CrossRefGoogle ScholarPubMed
Paoletti, P. and Neyton, J. (2007) NMDA receptor subunits: function and pharmacology. Current Opinion in Pharmacology 7, 39–47.CrossRefGoogle ScholarPubMed
Perrais, D., Pinheiro, P.S., Jane, D.E. and Mulle, C. (2009) Antagonism of recombinant and native GluK3-containing kainate receptors. Neuropharmacology 56, 131–140.CrossRefGoogle ScholarPubMed
Seifert, G., Rehn, L., Weber, M. and Steinhauser, C. (1997) AMPA receptor subunits expressed by single astrocytes in the juvenile mouse hippocampus. Brain Research. Molecular Brain Research 47, 286–294.CrossRefGoogle ScholarPubMed
Seifert, G. and Steinhauser, C. (1995) Glial cells in the mouse hippocampus express AMPA receptors with an intermediate Ca2+ permeability. European Journal of Neuroscience 7, 1872–1881.CrossRefGoogle ScholarPubMed
Takano, T., Kang, J., Jaiswal, J.K., Simon, S.M., Lin, J.H., Yu, Y. et al. (2005) Receptor-mediated glutamate release from volume sensitive channels in astrocytes. Proceedings of the National Academy of Sciences of the U.S.A. 102, 16466–16471.CrossRefGoogle ScholarPubMed
Tzingounis, A.V. and Wadiche, J.I. (2007) Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nature Reviews. Neuroscience 8, 935–947.CrossRefGoogle ScholarPubMed
Vignes, M. and Collingridge, G.L. (1997) The synaptic activation of kainate receptors. Nature 388, 179–182.CrossRefGoogle ScholarPubMed
Wondolowski, J. and Frerking, M. (2009) Subunit-dependent postsynaptic expression of kainate receptors on hippocampal interneurons in area CA1. Journal of Neuroscience 29, 563–574.CrossRefGoogle ScholarPubMed
Ye, Z.C., Wyeth, M.S., Baltan-Tekkok, S. and Ransom, B.R. (2003) Functional hemichannels in astrocytes: a novel mechanism of glutamate release. Journal of Neuroscience 23, 3588–3596.CrossRefGoogle ScholarPubMed
Yuan, X., Eisen, A.M., McBain, C.J. and Gallo, V. (1998) A role for glutamate and its receptors in the regulation of oligodendrocyte development in cerebellar tissue slices. Development 125, 2901–2914.CrossRefGoogle ScholarPubMed
Zalc, B. and Fields, R.D. (2000) Do action potentials regulate myelination?. Neuroscientist 6, 5–13.CrossRefGoogle ScholarPubMed
Zhou, M. and Kimelberg, H.K. (2000) Freshly isolated astrocytes from rat hippocampus show two distinct current patterns and different [K(+)](o) uptake capabilities. Journal of Neurophysiology 84, 2746–2757.CrossRefGoogle ScholarPubMed
Ziskin, J.L., Nishiyama, A., Rubio, M., Fukaya, M. and Bergles, D.E. (2007) Vesicular release of glutamate from unmyelinated axons in white matter. Nature Neuroscience 10, 321–330.CrossRefGoogle ScholarPubMed