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Pré-Publication, Document De Travail Année : 2021

Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration

Roman Serrat
  • Fonction : Auteur
Ana Covelo
  • Fonction : Auteur
Vladimir Kouskoff
Sebastien Delcasso
  • Fonction : Auteur
Andrea Ruiz
  • Fonction : Auteur
Nicolas Chenouard
Carol Stella
  • Fonction : Auteur
Corinne Blancard
Benedicte Salin
  • Fonction : Auteur
Francisca Julio-Kalajzić
  • Fonction : Auteur
Astrid Cannich
  • Fonction : Auteur
Federico Massa
  • Fonction : Auteur
Marjorie Varilh
  • Fonction : Auteur
Severine Deforges
Laurie Robin
  • Fonction : Auteur
Diego de Stefani
Arnau Busquets-Garcia
Anna Beyeler
  • Fonction : Auteur
Sandrine Pouvreau
  • Fonction : Auteur
Giovanni Marsicano

Résumé

Summary 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.

Dates et versions

hal-03429979 , version 1 (16-11-2021)

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Citer

Roman Serrat, Ana Covelo, Vladimir Kouskoff, Sebastien Delcasso, Andrea Ruiz, et al.. Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration. 2021. ⟨hal-03429979⟩

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