Endocannabinoids induce lateral long term potentiation of transmitter release by stimulation of gliotransmission Journal Article

Author(s): Gómez-Gonzalo, Marta; Navarrete, Marta; Perea, Gertrudis; Covelo, Ana; Martín-Fernández, Mario; Shigemoto, Ryuichi; Luján, Rafael; Araque, Alfonso
Article Title: Endocannabinoids induce lateral long term potentiation of transmitter release by stimulation of gliotransmission
Abstract: Endocannabinoids (eCBs) play key roles in brain function, acting as modulatory signals in synaptic transmission and plasticity. They are recognized as retrograde messengers that mediate long-term synaptic depression (LTD), but their ability to induce long-term potentiation (LTP) is poorly known. We show that eCBs induce the long-term enhancement of transmitter release at single hippocampal synapses through stimulation of astrocytes when coincident with postsynaptic activity. This LTP requires the coordinated activity of the 3 elements of the tripartite synapse: 1) eCB-evoked astrocyte calcium signal that stimulates glutamate release; 2) postsynaptic nitric oxide production; and 3) activation of protein kinase C and presynaptic group I metabotropic glutamate receptors, whose location at presynaptic sites was confirmed by immunoelectron microscopy. Hence, while eCBs act as retrograde signals to depress homoneuronal synapses, they serve as lateral messengers to induce LTP in distant heteroneuronal synapses through stimulation of astrocytes. Therefore, eCBs can trigger LTP through stimulation of astrocyte-neuron signaling, revealing novel cellular mechanisms of eCB effects on synaptic plasticity.
Keywords: Nitric Oxide; Astrocytes; LTP; endocannabinoid signaling; mGluRs
Journal Title: Cerebral Cortex
Volume: 25
Issue 10
ISSN: 1460-2199
Publisher: Oxford University Press  
Date Published: 2015-10-10
Start Page: 3699
End Page: 3712
DOI: 10.1093/cercor/bhu231
Notes: This work was supported by grants from Ministerio de Economia y Competitividad, Spain (MINECO; BFU2010-15832), European Union (HEALTH-F2-2007-202167), and Cajal Blue Brain to A.A. Grants from Spain (MINECO; BFU-2009-08404 and CSD2008-00005) to R.L. Grants from Spain (MINECO; Consolider, CSD2010-00045; Ramón y Cajal Program, RYC-2012-12014; and BFU2013-47265) to G.P. We thank Dr Atsu Aiba (Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo) for the donation of the mGluR1b rescue mice.
Open access: no