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A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation

Abstract

PHARMACOLOGICAL studies of long-term potentiation (LTP) in the hippocampus are starting to provide a molecular understanding of synaptic plastic processes which are believed to be important for learning and memory in vertebrates1. In the CA1 region of the hippocampus, the synaptic activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype is necessary for the induction of LTP under most experimental conditions2,3. The synaptic activation of metabotropic glutamate receptors (mGluRs) is also needed for the induction of LTP4,5. We now show that the role of mGluRs in the induction of LTP is fundamentally different from that of NMDA receptors. NMDA receptors initiate a molecular event that needs to be triggered each time a tetanus is delivered to induce LTP. In contrast, mGluRs activate a molecular switch which then negates the need for mGluR stimulation during the induction of LTP. This mGluR-activated switch is input-specific and can be turned off by a train of low-frequency stimulation. The molecular switch is a new feature of LTP which has fundamental consequences for our understanding of synaptic plastic mechanisms.

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References

  1. Bliss, T. V. P. & Collingridge, G. L. Nature 361, 31–39 (1993).

    Article  ADS  CAS  Google Scholar 

  2. Collingridge, G. L., Kehl, S. J. & McLennan, H. J. Physiol., Lond. 334, 33–46 (1983).

    Article  CAS  Google Scholar 

  3. Harris, E. W., Ganong, A. H. & Cotman, C. W. Brain Res. 323, 132–137 (1984).

    Article  CAS  Google Scholar 

  4. Bashir, Z. I. et al. Nature 363, 347–350 (1993).

    Article  ADS  CAS  Google Scholar 

  5. Sergueeva, O. A., Fedorov, N. B. & Reymann, K. G. Neuropharmacology 32, 933–935 (1993).

    Article  CAS  Google Scholar 

  6. Eaton, S. A. et al. Eur. J. Pharmac. molec. Pharmac. 244, 195–197 (1993).

    Article  CAS  Google Scholar 

  7. Jane, D. E. et al. Neuropharmacology 32, 725–727 (1993).

    Article  CAS  Google Scholar 

  8. Sladeczek, F., Pin, J.-P., Recasens, M., Bockaert, J. & Weiss, S. Nature 317, 717–719 (1985).

    Article  ADS  CAS  Google Scholar 

  9. Nicoletti, F. et al. J. Neurochem. 46, 40–46 (1986).

    Article  CAS  Google Scholar 

  10. Bortolotto, Z. A. & Collingridge, G. L. Neuropharmacology 32, 1–9 (1993).

    Article  CAS  Google Scholar 

  11. Bortolotto, Z. A., Anderson, W. W. & Collingridge, G. L. Soc. Neurosci. Abstr. 19, 547.5 (1993).

    Google Scholar 

  12. Reymann, K. G., Davies, S. N., Matthies, H., Kase, H. & Collingridge, G. L. Eur. J. Neurosci. 2, 481–486 (1990).

    Article  CAS  Google Scholar 

  13. Barrionuevo, G., Schottler, F. & Lynch, G. Life Sci. 27, 2385–2391 (1980).

    Article  CAS  Google Scholar 

  14. Fujii, S., Saito, K., Miyakawa, H., Ito, K. & Kato, H. Brain Res. 555, 112–122 (1991).

    Article  CAS  Google Scholar 

  15. Bashir, Z. I., Jane, D. E., Sunter D. C., Watkins, J. C. & Collingridge, G. L. Eur. J. Pharmac. 239, 265–266 (1993).

    Article  CAS  Google Scholar 

  16. Mulkey, R. M., Herron, C. E. & Malenka, R. C. Science 261, 1051–1055 (1993).

    Article  ADS  CAS  Google Scholar 

  17. Dudek, S. M. & Bear, M. F. Proc natn. Acad. Sci. U.S.A. 89, 4363–4367 (1992).

    Article  ADS  CAS  Google Scholar 

  18. Mulkey, R. M. & Malenka, R. C. Neuron 9, 967–975 (1992).

    Article  CAS  Google Scholar 

Download references

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Bortolotto, Z., Bashir, Z., Davies, C. et al. A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation. Nature 368, 740–743 (1994). https://doi.org/10.1038/368740a0

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