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

Serigy Sylantyev, Thomas P Jensen, Ruth A Ross, Dmitri A Rusakov

Research output: Contribution to journalArticlepeer-review


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 Ca(2+). However, the adaptive neurobiological significance of GPR55 remains unknown. Here, we use acute hippocampal slices and combine two-photon excitation Ca(2+) 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 Ca(2+) release from presynaptic Ca(2+) 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, Ca(2+) 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
JournalProceedings of the National Academy of Sciences
Issue number13
Publication statusPublished - 26 Mar 2013


  • Animals
  • CA1 Region, Hippocampal
  • CA3 Region, Hippocampal
  • Calcium
  • Cannabidiol
  • Cannabis
  • Inositol 1,4,5-Trisphosphate
  • Mice
  • Mice, Knockout
  • Microdissection
  • Neurotransmitter Agents
  • Presynaptic Terminals
  • Rats
  • Receptors, Cannabinoid
  • Receptors, G-Protein-Coupled
  • Synaptic Membranes
  • Synaptic Transmission


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