Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to cannabinoid receptors

Neuron. 2001 Aug 16;31(3):463-75. doi: 10.1016/s0896-6273(01)00375-0.


We report a type of synaptic modulation that involves retrograde signaling from postsynaptic metabotropic glutamate receptors (mGluRs) to presynaptic cannabinoid receptors. Activation of mGluR subtype 1 (mGluR1) expressed in cerebellar Purkinje cells (PCs) reduced neurotransmitter release from excitatory climbing fibers. This required activation of G proteins but not Ca2+ elevation in postsynaptic PCs. This effect was occluded by a cannabinoid agonist and totally abolished by cannabinoid antagonists. Depolarization-induced Ca2+ transients in PCs also caused cannabinoid receptor-mediated presynaptic inhibition. Thus, endocannabinoid production in PCs can be initiated by two distinct stimuli. Activation of mGluR1 by repetitive stimulation of parallel fibers, the other excitatory input to PCs, caused transient cannabinoid receptor-mediated depression of climbing fiber input. Our data highlight a signaling mechanism whereby activation of postsynaptic mGluR retrogradely influences presynaptic functions via endocannabinoid system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cannabinoid Receptor Modulators
  • Cannabinoids / metabolism*
  • Cerebellum / physiology*
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology*
  • In Vitro Techniques
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Promoter Regions, Genetic
  • Purkinje Cells / drug effects
  • Purkinje Cells / physiology*
  • Rats
  • Receptors, Cannabinoid
  • Receptors, Drug / drug effects
  • Receptors, Drug / physiology*
  • Receptors, Metabotropic Glutamate / deficiency
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Methoxyhydroxyphenylglycol
  • Calcium
  • 3,4-dihydroxyphenylglycol