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

83 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

Cite this

Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. / Sylantyev, Sergiy; Jensen, Thomas P.; Ross, Ruth A.; Rusakov, Dmitri A.

In: PNAS, Vol. 110, No. 13, 26.03.2013, p. 5193-5198.

Research output: Contribution to journalArticle

Sylantyev, Sergiy ; Jensen, Thomas P. ; Ross, Ruth A. ; Rusakov, Dmitri A. / Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. In: PNAS. 2013 ; Vol. 110, No. 13. pp. 5193-5198.
@article{3842a7ee4c214900979f0f45ec00305c,
title = "Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses",
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.",
keywords = "optical quantal analysis, long-term potentiation, mossy fiber synapses, synaptic-transmission, CA2+, facilitation, cannabidiol, plasticity, calcium, brain",
author = "Sergiy Sylantyev and Jensen, {Thomas P.} and Ross, {Ruth A.} and Rusakov, {Dmitri A.}",
year = "2013",
month = "3",
day = "26",
doi = "10.1073/pnas.1211204110",
language = "English",
volume = "110",
pages = "5193--5198",
journal = "PNAS",
issn = "0027-8424",
publisher = "NATL ACAD SCIENCES",
number = "13",

}

TY - JOUR

T1 - Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses

AU - Sylantyev, Sergiy

AU - Jensen, Thomas P.

AU - Ross, Ruth A.

AU - Rusakov, Dmitri A.

PY - 2013/3/26

Y1 - 2013/3/26

N2 - 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.

AB - 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.

KW - optical quantal analysis

KW - long-term potentiation

KW - mossy fiber synapses

KW - synaptic-transmission

KW - CA2+

KW - facilitation

KW - cannabidiol

KW - plasticity

KW - calcium

KW - brain

U2 - 10.1073/pnas.1211204110

DO - 10.1073/pnas.1211204110

M3 - Article

VL - 110

SP - 5193

EP - 5198

JO - PNAS

JF - PNAS

SN - 0027-8424

IS - 13

ER -