Postsynaptic endocannabinoid release is critical to long-term depression in the striatum

Nat Neurosci. 2002 May;5(5):446-51. doi: 10.1038/nn832.

Abstract

The striatum functions critically in movement control and habit formation. The development and function of cortical input to the striatum are thought to be regulated by activity-dependent plasticity of corticostriatal glutamatergic synapses. Here we show that the induction of a form of striatal synaptic plasticity, long-term depression (LTD), is dependent on activation of the CB1 cannabinoid receptor. LTD was facilitated by blocking cellular endocannabinoid uptake, and postsynaptic loading of anandamide (AEA) produced presynaptic depression. The endocannabinoid necessary for striatal LTD is thus likely to be released postsynaptically as a retrograde messenger. These findings demonstrate a new role for endocannabinoids in the induction of long-term synaptic plasticity in a circuit necessary for habit formation and motor control.

Publication types

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

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology
  • Cannabinoid Receptor Modulators
  • Cannabinoids / metabolism*
  • Cannabinoids / pharmacology
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dronabinol / analogs & derivatives
  • Electric Stimulation
  • Endocannabinoids
  • Excitatory Postsynaptic Potentials / drug effects
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug / deficiency
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism*
  • Synapses / metabolism*

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol
  • HU 211
  • anandamide