Associative short-term synaptic plasticity mediated by endocannabinoids

Neuron. 2005 Feb 3;45(3):419-31. doi: 10.1016/j.neuron.2004.12.045.


Associative learning is important on rapid timescales, but no suitable form of short-term plasticity has been identified that is both associative and synapse specific. Here, we assess whether endocannabinoids can mediate such plasticity. In the cerebellum, bursts of parallel fiber (PF) activity evoke endocannabinoid release from Purkinje cell dendrites that results in retrograde synaptic inhibition lasting seconds. We find that the powerful climbing fiber (CF) to Purkinje cell synapse regulates this inhibition. Compared to PF stimulation alone, coactivation of PF and CF synapses greatly enhanced endocannabinoid-mediated inhibition of PF synapses. Retrograde inhibition was restricted to PFs activated within several hundred milliseconds of CF activation. This associative plasticity reflects two aspects of calcium-dependent endocannabinoid release. First, PF-mediated activation of metabotropic glutamate receptors locally reduced the dendritic calcium levels required for endocannabinoid release. Second, CF and PF coactivation evoked localized supralinear dendritic calcium signals. Thus, endocannabinoids mediate transient associative synaptic plasticity.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Afferent Pathways / physiology
  • Animals
  • Calcium Signaling / physiology
  • Cannabinoid Receptor Modulators / physiology*
  • Cerebellar Cortex / cytology
  • Cerebellar Cortex / physiology*
  • Dendrites / physiology
  • Dendrites / ultrastructure
  • Electric Stimulation
  • Endocannabinoids*
  • Neural Inhibition / physiology
  • Neuronal Plasticity / physiology*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Purkinje Cells / cytology
  • Purkinje Cells / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / physiology
  • Receptors, Metabotropic Glutamate / physiology
  • Synapses / physiology*
  • Synaptic Transmission / physiology*


  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptors, Metabotropic Glutamate