title: Cannabinoid receptors contribute to astroglial Ca²⁺-signalling and control of synaptic plasticity in the neocortex.
abstract: Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying ATP release from astrocytes remain uncertain with exocytosis being the most intriguing and debated pathway. We have demonstrated that ATP and d-serine can be released from cortical astrocytes in situ by a SNARE-complex-dependent mechanism. Exocytosis of ATP from astrocytes can activate post-synaptic P2X receptors in the adjacent neurons, causing a downregulation of synaptic and extrasynaptic GABA receptors in cortical pyramidal neurons. We showed that release of gliotransmitters is important for the NMDA receptor-dependent synaptic plasticity in the neocortex. Firstly, induction of long-term potentiation (LTP) by five episodes of theta-burst stimulation (TBS) was impaired in the neocortex of dominant-negative (dn)-SNARE mice. The LTP was rescued in the dn-SNARE mice by application of exogenous non-hydrolysable ATP analogues. Secondly, we observed that weak sub-threshold stimulation (two TBS episodes) became able to induce LTP when astrocytes were additionally activated via CB-1 receptors. This facilitation was dependent on activity of ATP receptors and was abolished in the dn-SNARE mice. Our results strongly support the physiological relevance of glial exocytosis for glia-neuron communications and brain function.
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, UK.
authors.forename: Seyed
authors.initials: S
authors.lastname: Rasooli-Nejad
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, UK.
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, UK.
authors.forename: Ulyana
authors.initials: U
authors.lastname: Lalo
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, UK y.pankratov@warwick.ac.uk.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Pankratov
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D019579:Neocortex / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D043882:Receptors, Cannabinoid / Q000378:metabolism / Q000502:physiology*; D050600:SNARE Proteins / Q000235:genetics; D012694:Serine / Q000378:metabolism
chemical_list: D043882:Receptors, Cannabinoid; D050600:SNARE Proteins; D012694:Serine; D000255:Adenosine Triphosphate
keywords: LTP; d-serine; endocannabinoid; glia–neuron interaction; synaptic current; vesicular release