Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses

Sergiy Sylantyev, Thomas P. Jensen, Ruth A. Ross, Dmitri A. Rusakov*

*Corresponding author for this work

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

G protein-coupled receptor (GPR) 55 is sensitive to certain cannabinoids, it is expressed in the brain and, in cell cultures, it triggers mobilization of intracellular Ca2+. However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca2+ imaging in presynaptic axonal boutons with optical quantal analysis in postsynaptic dendritic spines to find that GPR55 activation transiently increases release probability at individual CA3-CA1 synapses. The underlying mechanism involves Ca2+ release from presynaptic Ca2+ stores, whereas postsynaptic stores (activated by spot-uncaging of inositol 1,4,5-trisphosphate) remain unaffected by GPR55 agonists. These effects are abolished by genetic deletion of GPR55 or by the GPR55 antagonist cannabidiol, a constituent of Cannabis sativa. GPR55 shows colocalization with synaptic vesicle protein vesicular glutamate transporter 1 in stratum radiatum. Short-term potentiation of CA3-CA1 transmission after a short train of stimuli reveals a presynaptic, Ca2+ store-dependent component sensitive to cannabidiol. The underlying cascade involves synthesis of phospholipids, likely in the presynaptic cell, but not the endocannabinoids 2-arachidonoylglycerol or anandamide. Our results thus unveil a signaling role for GPR55 in synaptic circuits of the brain.

Original languageEnglish
Pages (from-to)5193-5198
Number of pages6
JournalPNAS
Volume110
Issue number13
Early online date7 Mar 2013
DOIs
Publication statusPublished - 26 Mar 2013

Keywords

  • optical quantal analysis
  • long-term potentiation
  • mossy fiber synapses
  • synaptic-transmission
  • CA2+
  • facilitation
  • cannabidiol
  • plasticity
  • calcium
  • brain

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