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NMDA-receptor channel diversity in the developing cerebellum

Nature volume 368, pages 335–339 (1994)Cite this article

Abstract

IN the cerebellum, NMDA (N-methyl-d-aspartate) receptors play an important role in neuronal differentiation1,2 and excitatory synaptic transmission3–5. During early cerebellar development, marked changes occur in the distribution of messenger RNAs encoding various NMDA-receptor subunits6. To determine whether these changes result in the appearance of functionally distinct NMDA receptors7–9, we have recorded single-channel currents in rat cerebellar granule cells during the period of their migration from the external germinal layer to the inner granular layer10. Here we show that before synapse formation10,11, pre-migratory and migrating granule cells express NMDA receptors possessing single-channel properties similar to those previously described for many central neurons12-16. In contrast, mature post-migratory cells also express an atypical form of NMDA receptor that has a lower single-channel conductance and distinct kinetic behaviour. The properties of these 'low-conductance' channels correspond to those described17 for recombinant NMDA receptors formed by co-expression of NR1 and NR2C subunits8,9. The NR2C subunit appears postnatally and is found predominantly in the adult cerebellum6–8. Our data demonstrate developmental changes in NMDA-receptor properties at the single-channel level, and suggest that in the cerebellum the expression of a specific subunit protein results in a distinct form of native receptor.

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References

  1. Komuro, H. & Rakic, P. Science 260, 95–97 (1993).

    Article  ADS  CAS  Google Scholar 

  2. Rabacchi, S., Bailly, Y., Delhaye-Bouchaud, N. & Mariani, J. Science 256, 1823–1825 (1992).

    Article  ADS  CAS  Google Scholar 

  3. Garthwaite, J. & Brodbelt, A. R. Neuroscience 29, 401–412 (1989).

    Article  CAS  Google Scholar 

  4. Silver, R. A., Traynelis, S. F. & Cull-Candy, S. G. Nature 355, 163–166 (1992).

    Article  ADS  CAS  Google Scholar 

  5. D'Angelo, E., Rossi, P. & Taglietti, V. Neuroscience 53, 121–130 (1993).

    Article  CAS  Google Scholar 

  6. Watanabe, M., Inoue, Y., Sakimura, K. & Mishina, M. Neuroreport 3, 1138–1140 (1992).

    Article  CAS  Google Scholar 

  7. Kutsuwada, T. et al. Nature 358, 36–41 (1992).

    Article  ADS  CAS  Google Scholar 

  8. Monyer, H. et al. Science 256, 1217–1221 (1992).

    Article  ADS  CAS  Google Scholar 

  9. Ishii, T. et al. J. biol. Chem. 268, 2836–2843 (1993).

    CAS  Google Scholar 

  10. Altman, J. J. comp. Neurol. 145, 465–514 (1972).

    Article  CAS  Google Scholar 

  11. Hamori, J. & Somogyi, J. J. comp. Neurol. 220, 365–377 (1983).

    Article  CAS  Google Scholar 

  12. Nowak, L., Bregestovski, P., Ascher, P., Herbet, A. & Prochiantz, A. Nature 307, 462–465 (1984).

    Article  ADS  CAS  Google Scholar 

  13. Cull-Candy, S. G. & Usowicz, M. M. Nature 325, 525–528 (1987).

    Article  ADS  CAS  Google Scholar 

  14. Jahr, C. E. & Stevens, C. F. Nature 325, 522–525 (1987).

    Article  ADS  CAS  Google Scholar 

  15. Howe, J. R., Cull-Candy, S. G. & Colquhoun, D. J. Physiol., Lond. 432, 143–202 (1991).

    Article  CAS  Google Scholar 

  16. Gibb, A. J. & Colquhoun, D. J. Physiol., Lond. 456, 143–179 (1992).

    Article  CAS  Google Scholar 

  17. Stern, P., Béhé, P., Schoepfer, R. & Colquhoun, D. Proc. R. Soc. Lond. B250, 271–277 (1992).

    Article  ADS  CAS  Google Scholar 

  18. Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Pflügers Arch. 391, 85–100 (1981).

    Article  CAS  Google Scholar 

  19. Mayer, M. L., Westbrook, G. L. & Guthrie, P. B. Nature 309, 261–263 (1984).

    Article  ADS  CAS  Google Scholar 

  20. Garthwaite, G., Yamini, B. Jr & Garthwaite, J. Devl Brain Res. 36, 288–292 (1987).

    Article  CAS  Google Scholar 

  21. Blanton, M. G. & Kriegstein, A. R. J. Neurophysiol. 67, 1185–1200 (1992).

    Article  CAS  Google Scholar 

  22. Sah, P., Nicoll, R. A. & Hestrin, S. Science 246, 815–818 (1989).

    Article  ADS  CAS  Google Scholar 

  23. Carmignoto, G. & Vicini, S. Science 258, 1007–1011 (1992).

    Article  ADS  CAS  Google Scholar 

  24. Hestrin, S. Nature 357, 686–689 (1992).

    Article  ADS  CAS  Google Scholar 

  25. Mishina, M. et al. Nature 321, 406–411 (1986).

    Article  ADS  CAS  Google Scholar 

  26. Takahashi, T., Momiyama, A., Hirai, K., Hishinuma, F. & Akagi, H. Neuron 9, 1155–1161 (1992).

    Article  CAS  Google Scholar 

  27. Johnson, J. W. & Ascher, P. Nature 325, 529–531 (1987).

    Article  ADS  CAS  Google Scholar 

  28. Edwards, F. A., Konnerth, A., Sakmann, B. & Takahashi, T. Pflügers Arch. 414, 600–612 (1989).

    Article  CAS  Google Scholar 

  29. Colquhoun, D. & Sigworth, F. J. in Single-Channel Recording (eds Sakmann, B. & Neher, E.) 191–263 (Plenum, London, 1983).

    Book  Google Scholar 

  30. Sigworth, F. J. & Sine, S. M. Biophys. J. 52, 1047–1054 (1987).

    Article  CAS  Google Scholar 

  31. Rossi, D. J. & Slater, N. T. Neuropharmacology 32, 1239–1248 (1993).

    Article  CAS  Google Scholar 

Download references

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Author notes

  1. Tomoyuki Takahashi: Department of Neurophysiology, Institute of Brain Research, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan

Authors and Affiliations

  1. Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK

    Mark Farrant, Dirk Feldmeyer, Tomoyuki Takahashi & Stuart G. Cull-Candy

Authors
  1. Mark Farrant
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  2. Dirk Feldmeyer
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  3. Tomoyuki Takahashi
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  4. Stuart G. Cull-Candy
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Farrant, M., Feldmeyer, D., Takahashi, T. et al. NMDA-receptor channel diversity in the developing cerebellum. Nature 368, 335–339 (1994). https://doi.org/10.1038/368335a0

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