Depolarization-induced suppression of inhibition mediated by endocannabinoids at synapses from fast-spiking interneurons to medium spiny neurons in the striatum

Eur J Neurosci. 2006 Oct;24(8):2246-52. doi: 10.1111/j.1460-9568.2006.05119.x. Epub 2006 Oct 17.


Endogenous cannabinoids (endocannabinoids) act as retrograde inhibitory messengers in various regions of the brain. We have recently reported that endocannabinoids mediate short-term retrograde suppression of excitatory synaptic transmission from the neocortex to medium spiny (MS) neurons, the major projection neurons from the striatum. However, it remains unclear whether endocannabinoids modulate inhibitory transmission in the striatum. Here we show that depolarization of MS neurons induces transient suppression of inhibition that is mediated by retrograde endocannabinoid signalling. By paired recording from a fast-spiking (FS) interneuron and an MS neuron, we demonstrated that FS-MS inhibitory synapses undergo endocannabinoid-mediated retrograde suppression. We verified that GABAergic inhibitory terminals immunopositive for parvalbumin (PV), a marker for FS interneurons, expressed CB1 receptors. These PV-CB1 double-positive terminals surrounded dopamine D1 receptor-positive and D2 receptor-positive MS neurons; these constitute direct and indirect pathways, respectively. These results suggest that endocannabinoid-mediated retrograde suppression of inhibition influences information flow along both direct and indirect pathways, depending on the activity of MS neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cannabinoid Receptor Modulators / pharmacology*
  • Cell Shape
  • Electrophysiology
  • Endocannabinoids*
  • Excitatory Postsynaptic Potentials / drug effects
  • Immunohistochemistry
  • Interneurons / drug effects*
  • Membrane Potentials / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neostriatum / cytology
  • Neostriatum / drug effects*
  • Neurons / drug effects*
  • Neurons / ultrastructure
  • Patch-Clamp Techniques
  • Synapses / drug effects*
  • Synaptic Transmission / drug effects
  • gamma-Aminobutyric Acid / physiology


  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • gamma-Aminobutyric Acid