Astrocytes in endocannabinoid signalling

Abstract

Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour.

The endocannabinoid system in guarding against fear, anxiety and stress

“…3a). The eCB system and CB1R are also present and functional in astrocytes, thus eCB signalling is integrated into the concept of the ‘tripartite synapse’, including pre-and postsynaptic elements and surrounding astroglial processes 11,37 (FIG. 3b).…”

“…CB2R and possibly CB1R (indicated by a question mark) are also present on microglial cells and are involved in immune reactions 12 . Furthermore, whereas presynaptic CB1R is coupled to G o , CB1R on astrocytes is G q -coupled 11,37 . Thus, agonist stimulation of the receptor leads to an increase in intracellular Ca 2+ concentration, possibly with a concomitant release stimulation of ‘gliotransmitters’ (whose exact nature is not yet known, indicated by the question mark), finally modulating synaptic transmission 11,37 .…”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…The elevated Ca 2ϩ may then act as a cellular signal triggering chemical transmitters release, modulating in turn neuronal excitability and synaptic function, exchanging information with pre-and postsynaptic neurons, and leading to the concept of "the tripartite synapse" (20). Recent evidence shows that endocannabinoids and astroglial CB1 are new players in the tripartite synapse (619). CB1 in hippocampal astrocytes is activated by endocannabinoids released by neurons, with elevation of [Ca 2ϩ ] i through CB1-G q/11 signaling, and stimulation of astrocytic glutamate release and participation in synaptic plasticity (618).…”

Cannabinoids to treat spinal cord injury

“…1; Di Marzo and De Petrocellis, 2012). The endocannabinoids behave as retrograde messengers in synaptic plasticity and act as autocrine and paracrine signals between neurons and glial cells (Gomez et al, 2010;Di Marzo and De Petrocellis, 2012;Navarrete et al, 2014).…”