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 language | English |
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Pages (from-to) | 5193-5198 |
Number of pages | 6 |
Journal | PNAS |
Volume | 110 |
Issue number | 13 |
Early online date | 7 Mar 2013 |
DOIs | |
Publication status | Published - 26 Mar 2013 |
Keywords
- optical quantal analysis
- long-term potentiation
- mossy fiber synapses
- synaptic-transmission
- CA2+
- facilitation
- cannabidiol
- plasticity
- calcium
- brain