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.

  • Brief Communication
  • Published:

Endocannabinoids facilitate the induction of LTP in the hippocampus

Abstract

Exogenous cannabinoids disrupt behavioral learning and impede induction of long-term potentiation (LTP) in the hippocampus1, yet endogenous cannabinoids (endocannabinoids)2 transiently suppress inhibitory post-synaptic currents (IPSCs)3,4 by activating cannabinoid CB1 receptors on GABAergic interneurons5. We found that release of endocannabinoids by a rat CA1 pyramidal cell during this depolarization-induced suppression of inhibition (DSI)6,7 enabled a normally ineffective train of excitatory post-synaptic currents (EPSCs) to induce LTP in that cell, but not in neighboring cells. By showing that endocannabinoids facilitate LTP induction and help target LTP to single cells, these data shed new light on the physiological roles of endocannabinoids and may lead to a greater understanding of their effects on behavior and potential clinical use.

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

Access options

Buy this article

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

Figure 1: Induction of LTP in single CA1 pyramidal cells by a weak train preceded by a DSI-inducing voltage step.
Figure 2: The CB1R antagonist, AM-251 (2 μM), prevents LTP induced by the D + WT protocol, without affecting LTP induction.

Similar content being viewed by others

References

  1. Sullivan, J.M. Learn. Mem. 7, 132–139 (2000).

    Article  CAS  Google Scholar 

  2. Di Marzo, V., Melck, D., Bisogno, T. & De Petrocellis, L. Trends Neurosci. 21, 521–528 (1998).

    Article  CAS  Google Scholar 

  3. Wilson, R.I. & Nicoll, R.A. Nature 410, 588–592 (2001).

    Article  CAS  Google Scholar 

  4. Ohno-Shosaku, T., Maejima, T. & Kano, M. Neuron 29, 729–738 (2001).

    Article  CAS  Google Scholar 

  5. Katona, I. et al. J. Neurosci. 19, 4544–4558 (1999).

    Article  CAS  Google Scholar 

  6. Pitler, T.A. & Alger, B.E. J. Neurosci. 12, 4122–4132 (1992).

    Article  CAS  Google Scholar 

  7. Llano, I., Leresche, N. & Marty, A. Neuron 6, 565–574 (1991).

    Article  CAS  Google Scholar 

  8. Wagner, J.J. & Alger, B.E. J. Physiol. (Lond.) 495, 107–112 (1996).

    Article  CAS  Google Scholar 

  9. Wigstrom, H. & Gustafsson, B. Acta Physiol. Scand. 125, 159–172 (1985).

    Article  CAS  Google Scholar 

  10. Lenz, R.A. & Alger, B.E. J. Physiol. (Lond.) 521, 147–157 (1999).

    Article  CAS  Google Scholar 

  11. Malinow, R. & Tsien, R.W. Nature 346, 177–180 (1990).

    Article  CAS  Google Scholar 

  12. Le Beau, F.E.N. & Alger, B.E. J. Neurophysiol. 79, 659–669 (1998).

    Article  CAS  Google Scholar 

  13. Kandel, E.R. & Spencer, W.A. J. Neurophysiol. 24, 243–259 (1961).

    Article  CAS  Google Scholar 

  14. Ekstrom, A.D., Meltzer, J., McNaughton, B.L. & Barnes, C.A. Neuron 31, 631–638 (2001).

    Article  CAS  Google Scholar 

  15. Hájos, N., Ledent, C. & Freund, T.F. Neuroscience 106, 1–4 (2001).

    Article  Google Scholar 

Download references

Acknowledgements

We thank S. Thompson and D. Brager for reading a draft of this manuscript. This work was supported by US National Institutes of Health (NIH) grants NS36612 and NS30219 (to B.E.A.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bradley E. Alger.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carlson, G., Wang, Y. & Alger, B. Endocannabinoids facilitate the induction of LTP in the hippocampus. Nat Neurosci 5, 723–724 (2002). https://doi.org/10.1038/nn879

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn879

This article is cited by

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