Endocannabinoids facilitate the induction of LTP in the hippocampus

Nat Neurosci. 2002 Aug;5(8):723-4. doi: 10.1038/nn879.


Exogenous cannabinoids disrupt behavioral learning and impede induction of long-term potentiation (LTP) in the hippocampus, yet endogenous cannabinoids (endocannabinoids) transiently suppress inhibitory post-synaptic currents (IPSCs) by activating cannabinoid CB1 receptors on GABAergic interneurons. We found that release of endocannabinoids by a rat CA1 pyramidal cell during this depolarization-induced suppression of inhibition (DSI) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cannabinoid Receptor Modulators
  • Cannabinoids / pharmacology*
  • Electric Stimulation / methods
  • Endocannabinoids
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Antagonists
  • Hippocampus / drug effects*
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Long-Term Potentiation / physiology*
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Rats


  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • GABA Antagonists
  • GABA-A Receptor Antagonists