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Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus

Nature volume 405, pages 187–191 (2000)Cite this article

Abstract

Fast excitatory neurotransmission in the central nervous system occurs at specialized synaptic junctions between neurons, where a high concentration of glutamate directly activates receptor channels. Low-affinity AMPA (α-amino-3-hydroxy-5-methyl isoxazole propionic acid) and kainate glutamate receptors are also expressed by some glial cells1, including oligodendrocyte precursor cells (OPCs). However, the conditions that result in activation of glutamate receptors on these non-neuronal cells are not known. Here we report that stimulation of excitatory axons in the hippocampus elicits inward currents in OPCs that are mediated by AMPA receptors. The quantal nature of these responses and their rapid kinetics indicate that they are produced by the exocytosis of vesicles filled with glutamate directly opposite these receptors. Some of these AMPA receptors are permeable to calcium ions, providing a link between axonal activity and internal calcium levels in OPCs. Electron microscopic analysis revealed that vesicle-filled axon terminals make synaptic junctions with the processes of OPCs in both the young and adult hippocampus. These results demonstrate the existence of a rapid signalling pathway from pyramidal neurons to OPCs in the mammalian hippocampus that is mediated by excitatory, glutamatergic synapses.

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Figure 1: Synaptic responses from identified OPCs in hippocampal slices.
Figure 2: Properties of excitatory responses in OPCs.
Figure 3: Quantal EPSCs in OPCs are elicited by a brief, high concentration of glutamate.
Figure 4: Excitatory synaptic responses were evoked in OPCs from both young and adult animals.
Figure 5: Electron micrographs of the synaptic relationships of OPCs.

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References

  1. Steinhauser, C. & Gallo, V. News on glutamate receptors in glial cells. Trends Neurosci. 19, 339–345 (1996).

    Article  CAS  Google Scholar 

  2. Miller, R. H. Oligodendrocyte origins. Trends Neurosci. 19, 92–96 (1996).

    Article  CAS  Google Scholar 

  3. Palay, S. L. & Chan-Palay, V. Cerebellar Cortex, Cytology and Organization (Springer, New York, 1974).

    Book  Google Scholar 

  4. Raff, M. C., Miller, R. H. & Noble, M. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303, 390–396 (1983).

    Article  ADS  CAS  Google Scholar 

  5. Patneau, D. K., Wright, P. W., Winters, C., Mayer, M. L. & Gallo, V. Glial cells of the oligodendrocyte lineage express both kainate- and AMPA-preferring subtypes of glutamate receptor. Neuron 12, 357–371 (1994).

    Article  CAS  Google Scholar 

  6. Wyllie, D. J., Mathie, A., Symonds, C. J. & Cull-Candy, S. G. Activation of glutamate receptors and glutamate uptake in identified macroglial cells in rat cerebellar cultures. J. Physiol.(Lond.) 432, 235–258 (1991).

    Article  CAS  Google Scholar 

  7. Barres, B. A. & Raff, M. C. Control of oligodendrocyte number in the developing rat optic nerve. Neuron 12, 935–942 (1994).

    Article  CAS  Google Scholar 

  8. Gallo, V. et al. Oligodendrocyte progenitor cell proliferation and lineage progression are regulated by glutamate receptor-mediated K+ channel block. J. Neurosci. 16, 2659–2670 (1996).

    Article  CAS  Google Scholar 

  9. McDonald, J. W., Levine, J. M. & Qu, Y. Multiple classes of the oligodendrocyte lineage are highly vulnerable to excitotoxicity. Neuroreport 9, 2757–2762 (1998).

    Article  CAS  Google Scholar 

  10. Bergles, D. E., Diamond, J. S. & Jahr, C. E. Clearance of glutamate inside the synapse and beyond. Curr. Opin. Neurobiol. 9, 293–298 (1999).

    Article  CAS  Google Scholar 

  11. Kriegler, S. & Chiu, S. Y. Calcium signaling of glial cells along mammalian axons. J. Neurosci. 13, 4229–4245 (1993).

    Article  CAS  Google Scholar 

  12. Ong, W. Y. & Levine, J. M. A light and electron microscopic study of NG2 chondroitin sulfate proteoglycan-positive oligodendrocyte precursor cells in the normal and kainate-lesioned rat hippocampus. Neurosci. 92, 83–95 (1999).

    Article  CAS  Google Scholar 

  13. Dingledine, R., Borges, K., Bowie, D. & Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61 (1999).

    CAS  PubMed  Google Scholar 

  14. Zerangue, N. & Kavanaugh, M. P. Flux coupling in a neuronal glutamate transporter. Nature 383, 634–637 (1996).

    Article  ADS  CAS  Google Scholar 

  15. Dunwiddie, T. V. The physiological role of adenosine in the central nervous system. Int. Rev. Neurobiol. 27, 63–139 (1985).

    Article  CAS  Google Scholar 

  16. Amaral, D. G. & Witter, M. P. The three dimensional organization of the hippocampal formation: a review of anatomical data. Neurosci. 31, 571–591 (1989).

    Article  CAS  Google Scholar 

  17. Lisman, J. E. & Harris, K. M. Quantal analysis and synaptic anatomy - integrating two views of hippocampal plasticity. Trends Neurosci. 16, 141–147 (1993).

    Article  CAS  Google Scholar 

  18. Renner, P., Caratsch, C. G., Waser, P. G., Lazarovici, P. & Primor, N. Presynaptic effects of the pardaxins, polypeptides isolated from the gland secretion of the flatfish Pardachirus Marmoratus. Neurosci. 23, 319–325 (1987).

    Article  CAS  Google Scholar 

  19. Hessler, N. A., Shirke, A. M. & Malinow, R. The probability of transmitter release at a mammalian central synapse. Nature 366, 569–572 (1993).

    Article  ADS  CAS  Google Scholar 

  20. Dzubay, J. A. & Jahr, C. E. The concentration of synaptically released glutamate outside of the climbing fiber-purkinje cell synaptic cleft. J. Neurosci. 19, 5265–5274 (1999).

    Article  CAS  Google Scholar 

  21. Ventura, R. & Harris, K. M. Three-dimensional relationships between hippocampal synapses and astrocytes. J. Neurosci. 19, 6897–6906 (1999).

    Article  CAS  Google Scholar 

  22. Bergles, D. E., Dzubay, J. A. & Jahr, C. E. Glutamate transporter currents in bergmann glial cells follow the time course of extrasynaptic glutamate. Proc. Natl Acad. Sci. USA 94, 14821–14825 (1997).

    Article  ADS  CAS  Google Scholar 

  23. Wang, S. et al. Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21, 63–75 (1998).

    Article  Google Scholar 

  24. Keirstead, H. S., Levine, J. M. & Blakemore, W. F. Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord. Glia 22, 161–170 (1998).

    Article  CAS  Google Scholar 

  25. Wolswijk, G. Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J. Neurosci. 18, 601–609 (1998).

    Article  CAS  Google Scholar 

  26. Bergles, D. E. & Jahr, C. E. Synaptic activation of glutamate transporters in hippocampal astrocytes. Neuron 19, 1297–1308 (1997).

    Article  CAS  Google Scholar 

  27. Tillet, E., Ruggiero, F., Nishiyama, A. & Stallcup, W. B. The membrane-spanning proteoglycan NG2 binds to collagens V and VI through the central nonglobular domain of its core protein. J. Biol. Chem. 272, 10769–10776 (1997).

    Article  CAS  Google Scholar 

  28. Stallcup, W. B., Dahlin, K. & Healy, P. Interaction of the NG2 chondroitin sulfate proteoglycan with type VI collagen. J. Cell Biol. 111, 3177–3188 (1990).

    Article  CAS  Google Scholar 

  29. Reyes, A. et al. Target-cell-specific facilitation and depression in neocortical circuits. Nature Neurosci. 1, 279–285 (1998).

    Article  CAS  Google Scholar 

  30. Baude, A. et al. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11, 771–787 (1993).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank P. Cobden and P. Jays for assistance. This work was supported by the UK Medical Research Council (P.S.) and the NIH (C.E.J.).

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Authors and Affiliations

  1. Vollum Institute, L474, Oregon Health Sciences University, Portland, 97201, Oregon, USA

    Dwight E. Bergles & Craig E. Jahr

  2. Department of Pharmacology, MRC Anatomical Neuropharmacology Unit, University of Oxford, Oxford, OX1 3TH, UK

    J. David B. Roberts & Peter Somogyi

Authors
  1. Dwight E. Bergles
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  2. J. David B. Roberts
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  3. Peter Somogyi
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  4. Craig E. Jahr
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Correspondence to Dwight E. Bergles.

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Bergles, D., Roberts, J., Somogyi, P. et al. Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405, 187–191 (2000). https://doi.org/10.1038/35012083

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