RT Journal Article
SR Electronic
T1 Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.08.415620
DO 10.1101/2020.12.08.415620
A1 Roman Serrat
A1 Ana Covelo
A1 Vladimir Kouskoff
A1 Sebastien Delcasso
A1 Andrea Ruiz
A1 Nicolas Chenouard
A1 Carol Stella
A1 Corinne Blancard
A1 Benedicte Salin
A1 Francisca Julio-Kalajzić
A1 Astrid Cannich
A1 Federico Massa
A1 Marjorie Varilh
A1 Severine Deforges
A1 Laurie M. Robin
A1 Diego De Stefani
A1 Arnau Busquets-Garcia
A1 Frederic Gambino
A1 Anna Beyeler
A1 Sandrine Pouvreau
A1 Giovanni Marsicano
YR 2020
UL http://biorxiv.org/content/early/2020/12/08/2020.12.08.415620.abstract
AB 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 currently unexplored. We found that the activation of astrocyte mitochondrial-associated CB1 receptors (mtCB1) determines MERCs-dependent intracellular calcium signaling and synaptic integration. The stimulation of mtCB1 receptors promotes calcium transfer from the endoplasmic reticulum to mitochondria through specific mechanisms regulating the activity of the mitochondrial calcium uniporter (MCU) channel. Physiologically, mtCB1-dependent mitochondrial calcium uptake determines the precise dynamics of cytosolic calcium events in astrocytes upon endocannabinoid mobilization. Accordingly, electrophysiological recordings in hippocampal slices showed that genetic exclusion of mtCB1 receptors or specific astroglial MCU inhibition blocks lateral synaptic potentiation, a key example of astrocyte-dependent integration of distant synapses activity. Altogether, these data reveal an unforeseen link between astroglial MERCs and the regulation of brain network functions.Competing Interest StatementThe authors have declared no competing interest.