Presynaptic specificity of endocannabinoid signaling in the hippocampus

Neuron. 2001 Aug 16;31(3):453-62. doi: 10.1016/s0896-6273(01)00372-5.


Endocannabinoids are retrograde messengers released by neurons to modulate the strength of their synaptic inputs. Endocannabinoids are thought to mediate the suppression of GABA release that follows depolarization of a hippocampal CA1 pyramidal neuron-termed "depolarization-induced suppression of inhibition" (DSI). Here, we report that DSI is absent in mice which lack cannabinoid receptor-1 (CB1). Pharmacological and kinetic evidence suggests that CB1 activation inhibits presynaptic Ca2+ channels through direct G protein inhibition. Paired recordings show that endocannabinoids selectively inhibit a subclass of synapses distinguished by their fast kinetics and large unitary conductance. Furthermore, cannabinoid-sensitive inputs are unusual among central nervous system synapses in that they use N- but not P/Q-type Ca2+ channels for neurotransmitter release. These results indicate that endocannabinoids are highly selective, rapid modulators of hippocampal inhibition.

Publication types

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

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / physiology
  • Cannabinoid Receptor Modulators
  • Cannabinoids / metabolism*
  • Colforsin / pharmacology
  • Endocannabinoids
  • Female
  • GTP-Binding Proteins / metabolism
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Interneurons / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Patch-Clamp Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / deficiency
  • Receptors, Drug / genetics
  • Receptors, Drug / physiology*
  • Receptors, Presynaptic / drug effects
  • Receptors, Presynaptic / physiology*
  • Signal Transduction


  • Calcium Channel Blockers
  • Calcium Channels
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Receptors, Presynaptic
  • Colforsin
  • GTP-Binding Proteins