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Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration [article]

Roman Serrat, Ana Covelo, Vladimir Kouskoff, Sebastien Delcasso, Andrea Ruiz, Nicolas Chenouard, Carol Stella, Corinne Blancard, Benedicte Salin, Francisca Julio-Kalajzic, Astrid Cannich, Federico Massa (+9 others)
2020 biorxiv/medrxiv   pre-print

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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
more » ... 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.
doi:10.1101/2020.12.08.415620 fatcat:5tfsmebqfvfsnigepwqncoz27m
Citation

Roman Serrat, Ana Covelo, Vladimir Kouskoff, Sebastien Delcasso, Andrea Ruiz, Nicolas Chenouard, Carol Stella, Corinne Blancard, Benedicte Salin, Francisca Julio-Kalajzic, Astrid Cannich, Federico Massa, Marjorie Varilh, Severine Deforges, Laurie Robin, Diego Destefani, Arnau Busquets-Garcia, Frederic Gambino, Anna Beyeler, Sandrine Pouvreau, Giovanni Marsicano. "Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration." biorxiv/medrxiv (2020)