Postsynaptic TRPV1 triggers cell type-specific long-term depression in the nucleus accumbens

Nat Neurosci. 2010 Dec;13(12):1519-25. doi: 10.1038/nn.2685. Epub 2010 Nov 14.


Synaptic modifications in the nucleus accumbens (NAc) are important for adaptive and pathological reward-dependent learning. Medium spiny neurons (MSNs), the major cell type in the NAc, participate in two parallel circuits that subserve distinct behavioral functions, yet little is known about differences in their electrophysiological and synaptic properties. Using bacterial artificial chromosome transgenic mice, we found that synaptic activation of group I metabotropic glutamate receptors in NAc MSNs in the indirect, but not direct, pathway led to the production of endocannabinoids, which activated presynaptic CB1 receptors to trigger endocannabinoid-mediated long-term depression (eCB-LTD) as well as postsynaptic transient receptor potential vanilloid 1 (TRPV1) channels to trigger a form of LTD resulting from endocytosis of AMPA receptors. These results reveal a previously unknown action of TRPV1 channels and indicate that the postsynaptic generation of endocannabinoids can modulate synaptic strength in a cell type-specific fashion by activating distinct pre- and postsynaptic targets.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cocaine / pharmacology
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nucleus Accumbens / cytology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Synaptic Potentials / drug effects
  • Synaptic Potentials / physiology*
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / physiology*


  • Piperidines
  • Pyrazoles
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • AM 251
  • Cocaine