Retrograde endocannabinoid signaling in the cerebellar cortex

Cerebellum. 2006;5(2):134-45. doi: 10.1080/14734220600791477.


The regulation of Purkinje cell activity is important for motor behavior and motor learning. As the sole output cell of the cerebellar cortex, Purkinje cell firing is controlled by parallel fibers and climbing fiber synapses, and by inhibitory interneurons. Depolarization of Purkinje cells evokes endocannabinoid release that activates cannabinoid CB1 receptors expressed on boutons of its synaptic inputs to transiently decrease neurotransmitter release. In addition, associative activation of the excitatory inputs can liberate endocannabinoids to decrease synaptic strength for a prolonged duration. Here we review the different mechanisms of evoking endocannabinoid release and discuss the physiological role of endocannabinoids in mediating global modulation of synaptic strength, localized short-term associative plasticity and cerebellar long term depression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cannabinoid Receptor Modulators / metabolism*
  • Cerebellar Cortex / cytology
  • Cerebellar Cortex / metabolism*
  • Endocannabinoids*
  • Humans
  • Interneurons / metabolism
  • Interneurons / ultrastructure
  • Neural Pathways / cytology
  • Neural Pathways / metabolism*
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Purkinje Cells / cytology
  • Purkinje Cells / metabolism*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Signal Transduction / physiology*
  • Synaptic Transmission / physiology*


  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1