Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration
Cell Reports. 2021-12-01; 37(12): 110133
DOI: 10.1016/j.celrep.2021.110133
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Serrat R(1), Covelo A(2), Kouskoff V(3), Delcasso S(4), Ruiz-Calvo A(2), Chenouard N(3), Stella C(2), Blancard C(5), Salin B(5), Julio-Kalajzić F(2), Cannich A(2), Massa F(2), Varilh M(2), Deforges S(3), Robin LM(2), De Stefani D(6), Busquets-Garcia A(2), Gambino F(3), Beyeler A(2), Pouvreau S(7), Marsicano G(8).
Author information:
(1)Institut National de la Santé et de la Recherche Médicale (INSERM), U1215
NeuroCentre Magendie, 33077 Bordeaux, France; University of Bordeaux, 33077
Bordeaux, France; INRAE, Nutrition and Integrative Neurobiology, UMR 1286,
Bordeaux, France.
(2)Institut National de la Santé et de la Recherche Médicale (INSERM), U1215
NeuroCentre Magendie, 33077 Bordeaux, France; University of Bordeaux, 33077
Bordeaux, France.
(3)University of Bordeaux, 33077 Bordeaux, France; Interdisciplinary Institute
for Neuroscience, CNRS UMR 5297, 33000 Bordeaux, France.
(4)Institut National de la Santé et de la Recherche Médicale (INSERM), U1215
NeuroCentre Magendie, 33077 Bordeaux, France; University of Bordeaux, 33077
Bordeaux, France; Institut de Biochimie et Genetique Cellulaires, CNRS UMR 5095,
Bordeaux, France.
(5)University of Bordeaux, 33077 Bordeaux, France; Institut de Biochimie et
Genetique Cellulaires, CNRS UMR 5095, Bordeaux, France.
(6)Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy.
(7)Institut National de la Santé et de la Recherche Médicale (INSERM), U1215
NeuroCentre Magendie, 33077 Bordeaux, France; University of Bordeaux, 33077
Bordeaux, France; Interdisciplinary Institute for Neuroscience, CNRS UMR 5297,
33000 Bordeaux, France. Electronic address: .
(8)Institut National de la Santé et de la Recherche Médicale (INSERM), U1215
NeuroCentre Magendie, 33077 Bordeaux, France; University of Bordeaux, 33077
Bordeaux, France. Electronic address: .
Erratum in
Cell Rep. 2022 Oct 11;41(2):111499.
Intracellular calcium signaling underlies the astroglial control of synaptic
transmission and plasticity. Mitochondria-endoplasmic reticulum contacts (MERCs)
are key determinants of calcium dynamics, but their functional impact on
astroglial regulation of brain information processing is unexplored. We found
that the activation of astrocyte mitochondrial-associated type-1 cannabinoid
(mtCB1) receptors determines MERC-dependent intracellular calcium signaling and
synaptic integration. The stimulation of mtCB1 receptors promotes calcium
transfer from the endoplasmic reticulum to mitochondria through a specific
molecular cascade, involving the mitochondrial calcium uniporter (MCU).
Physiologically, mtCB1-dependent mitochondrial calcium uptake determines the
dynamics of cytosolic calcium events in astrocytes upon endocannabinoid
mobilization. Accordingly, electrophysiological recordings in hippocampal slices
showed that conditional genetic exclusion of mtCB1 receptors or
dominant-negative MCU expression in astrocytes blocks lateral synaptic
potentiation, through which astrocytes integrate the activity of distant
synapses. Altogether, these data reveal an endocannabinoid link between
astroglial MERCs and the regulation of brain network functions.
Copyright © 2021. Published by Elsevier Inc.