Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

GABAB autoreceptors regulate the induction of LTP

Nature volume 349, pages 609–611 (1991)Cite this article

Abstract

UNDERSTANDING the mechanisms involved in long-term potenti-ation (LTP) should provide insights into the cellular and molecular basis of learning and memory in vertebrates1. It has been established that in the CA1 region of the hippocampus the induction of LTP requires the transient activation of the N-methyl-D-aspartate (NMDA) receptor system2. During low-frequency transmission, significant activation of this system is prevented by γ-aminobutyric acid (GABA) mediated synaptic inhibition3,4 which hyperpolarizes neurons into a region where NMDA receptor-operated channels are substantially blocked by Mg2+ (refs. 5, 6). But during high-frequency transmission, mechanisms are evoked that provide sufficient depolarization of the postsynaptic membrane to reduce this block7 and thereby permit the induction of LTP. We now report that this critical depolarization is enabled because during high-frequency transmission GABA depresses its own release by an action on GABAB autoreceptors, which permits sufficient NMDA receptor activation for the induction of LTP. These findings demonstrate a role for GABAB receptors in synaptic plasticity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Bliss, T. V. P. & Lynch, M. A. Neurol Neurobiol. 35, 3–72 (1988).

    Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Dingledine, R., Hynes, M. A. & King, G. L., J. Physiol., Lond. 380, 175–189 (1986).

    Article  CAS  Google Scholar 

  4. Collingridge, G. L., Herron, C. E. & Lester, R. A. J. J. Physiol., Lond. 399, 283–300 (1988).

    Article  CAS  Google Scholar 

  5. Ascher, P. & Nowak, L. J. Physiol., Lond. 399, 247–266 (1988).

    Article  CAS  Google Scholar 

  6. Mayer, M. L. & Westbrook, G. L. J. Physiol., Lond. 361, 65–90 (1985).

    Article  CAS  Google Scholar 

  7. Collingridge, G. L., Herron, C. E. & Lester, R. A. J. J. Physiol., Lond. 399, 301–312 (1988).

    Article  CAS  Google Scholar 

  8. Ben-Ari, Y., Krnjevic, K. & Reinhardt, W. Can. J. Physiol. Pharmacol. 57, 1462–1466 (1979).

    Article  CAS  Google Scholar 

  9. McCarren, M. & Alger, B. E. J. Neurophysiol. 53, 557–571 (1985).

    Article  CAS  Google Scholar 

  10. Harrison, N. L. J. Physiol., Lond. 422, 433–446 (1990).

    Article  CAS  Google Scholar 

  11. Davies, C. H., Davies, S. N. & Collingridge, G. L. J. Physiol., Lond. 424, 513–531 (1990).

    Article  CAS  Google Scholar 

  12. Olpe, H.-R. et al. Eur. J. Pharmac. 187, 27–38 (1990).

    Article  CAS  Google Scholar 

  13. Larson, J. & Lynch, G. Brain Res. 441, 111–118 (1988).

    Article  CAS  Google Scholar 

  14. Diamond, D. M., Dunwiddie, T. V. & Rose, G. M. J. Neurosci. 8, 4079–4088 (1988).

    Article  CAS  Google Scholar 

  15. Coan, E. J. & Collingridge, G. L. Neurosci. Lett. 53, 21–26 (1985).

    Article  CAS  Google Scholar 

  16. Lanthorn, T. H. & Cotman, C. W. Brain Res. 225, 171–178 (1981).

    Article  CAS  Google Scholar 

  17. Randall, A. D., Schofield, J. G., Davies, C. H. & Collingridge, G. L. J. Physiol., Lond. 426, 51P (1990).

    Google Scholar 

  18. Dutar, P. & Nicoll, R. A. Nature 332, 156–158 (1988).

    Article  ADS  CAS  Google Scholar 

  19. Dutar, P. & Nicoll, R. A. Neuron 1, 585–591 (1988).

    Article  CAS  Google Scholar 

  20. Wigström, H. & Gustafsson, B. Nature 301, 603–604 (1983).

    Article  ADS  Google Scholar 

  21. Mott, D. D., Lewis, D. V., Ferrari, C. M., Wilson, W. A. & Swartzwelder, H. S. Neurosci. Lett. 113, 222–226 (1990).

    Article  CAS  Google Scholar 

  22. Olpe, H.-R. & Karlsson, G. Naunyn-Schmiedebergs Archs Pharmak. 342, 194–197 (1990).

    Article  CAS  Google Scholar 

  23. Deisz, R. A. & Prince, D. A. J. Physiol., Lond. 412, 513–542 (1989).

    Article  CAS  Google Scholar 

  24. Kauer, J. A., Malenka, R. C. & Nicoll, R. A. Neuron 1, 911–917 (1988).

    Article  CAS  Google Scholar 

  25. Muller, D., Joly, M. & Lynch, G. Science 242, 1694–1697 (1988).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Sarah J. Starkey

    Present address: Department of Neuropharmacology, Glaxo Research Ltd, Ware, Herts, SG12 ODJ, UK

  2. Mario F. Pozza

    Present address: Ciba-Geigy Ltd, Research Department, Pharmaceuticals Division, K-125.7.09 + 7.13, CH-4002, Basle, Switzerland

  3. Graham L. Collingridge: To whom correspondence should be addressed at the University of Birmingham

Authors and Affiliations

  1. Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS81TD, UK

    Ceri H. Davies, Sarah J. Starkey, Mario F. Pozza & Graham L. Collingridge

  2. Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Ceri H. Davies & Graham L. Collingridge

Authors
  1. Ceri H. Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah J. Starkey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mario F. Pozza
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Graham L. Collingridge
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davies, C., Starkey, S., Pozza, M. et al. GABAB autoreceptors regulate the induction of LTP. Nature 349, 609–611 (1991). https://doi.org/10.1038/349609a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/349609a0

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing