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Review
. 2014 Oct 19;369(1654):20130599.
doi: 10.1098/rstb.2013.0599.

Astrocytes in endocannabinoid signalling

Marta Navarrete  1 , Adolfo Díez  1 , Alfonso Araque  2
Affiliations
Review

Astrocytes in endocannabinoid signalling

Marta Navarrete et al. Philos Trans R Soc Lond B Biol Sci. .

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.

Keywords: astrocytes; communication; endocannabinoids; gliotransmitter release; neuron–glia; tripartite synapses.

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Figures

Figure 1.
Figure 1.
Endocannabinoids released by neurons elevate calcium and stimulate glutamate release in astrocytes. (a) Stimulating ECB release by neuronal depolarization (ND; horizontal bar) of a CA1 hippocampal pyramidal neuron elevates astrocyte Ca2+ levels (red traces) and increase the number of slow inward currents (SICs; marked with asterisks) in an adjacent neuron (black trace); a single SIC is expanded (blue trace). (b) The astrocyte Ca2+ spike probability (red) and the mean number of neuronal SICs (blue) were enhanced after the neuronal depolarization (horizontal bar). (c) Schematic drawing representing the ECB-mediated neuron–astrocyte signalling and the subsequent glutamate-mediated astrocyte–neuron communication. Adapted from [9].
Figure 2.
Figure 2.
Astrocytes spatially control the synaptic regulation induced by neuron released endocannabinoids. (a) Recording from two CA1 hippocampal pyramidal neurons while simultaneously monitoring astrocyte calcium levels and synaptic transmission properties in single synapses and adjacent neuron (heteroneuronal synapses). ECBs released after depolarization of one neuron depressed or enhanced the probability of neurotransmitter release depending on the distance to the ECB source. (b) While ECBs released by neuronal depolarization (ND) depressed excitatory synaptic currents into the depolarized neuron (homoneuronal synapses; green traces), they enhanced synaptic transmission in adjacent neruons (heteroneuronal synapses; blue traces). (c) Scheme representing the ECB signalling processes that regulates hippocampal synaptic transmission. ECBs released by the post-synaptic neuron directly activate CB1Rs in the pre-synaptic terminal, which leads to synaptic depression in homoneuronal synapses (DSE). In addition, they activate CB1Rs in astrocytes, elevate their intracellular Ca2+ and stimulate the release of glutamate that potentiates neurotransmitter release in heteroneuronal synapses (e-SP). Adapted from [10].
Figure 3.
Figure 3.
Signalling mechanisms underlying synaptic regulation by endocannbinoids through stimulation of astrocytes. (a) In the hippocampus, ECBs released by one active pyramidal neuron act directly on pre-synaptic CB1Rs of the synaptic terminals received leading to DSE in homoneuronal synapses. In addition, ECBs activate CB1Rs in astrocytes (1), elevating their intracellular Ca2+ and stimulating the relase of glutamate (2), which potentiates neurotransmitter release in heteroneuronal synapses (3). (b) In the cortex, the coincidence of post-synaptic metabotropic glutamate receptor (mGluR) activation during synaptic activity and Ca2+ influx evoked by back-propagating action potentials in the post-synaptic cell induces the release of ECBs that activate CB1 receptors in astrocytes (1), which stimulates the release of glutamate (2) that activates pre-synaptic NMDA receptors and induces LTD (3). (c) Activation of astrocyte CB1Rs by exogenous cannabinoids (1) stimulate the release of glutamate (2), which activates post-synaptic NMDA receptors (3) that induce the endocytosis of post-synaptic AMPA receptors that leads to LTD. (a–c Adapted from [10,11,54], respectively.)
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