2. Academic Validation
  3. Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration

Astroglial ER-mitochondria calcium transfer mediates endocannabinoid-dependent synaptic integration

  • Cell Rep. 2021 Dec 21;37(12):110133. doi: 10.1016/j.celrep.2021.110133.
Roman Serrat 1,  Ana Covelo 2,  Vladimir Kouskoff 3,  Sebastien Delcasso 4,  Andrea Ruiz-Calvo 2,  Nicolas Chenouard 3,  Carol Stella 2,  Corinne Blancard 5,  Benedicte Salin 5,  Francisca Julio-Kalajzić 2,  Astrid Cannich 2,  Federico Massa 2,  Marjorie Varilh 2,  Severine Deforges 3,  Laurie M Robin 2,  Diego De Stefani 6,  Arnau Busquets-Garcia 2,  Frederic Gambino 3,  Anna Beyeler 2,  Sandrine Pouvreau 7,  Giovanni Marsicano 8
Affiliations

Affiliations

  • 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: sandrine.pouvreau@u-bordeaux.fr.
  • 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: giovanni.marsicano@inserm.fr.
PMID: 34936875 DOI: 10.1016/j.celrep.2021.110133
Abstract

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.

Keywords

CB1; MERCs; astrocytes; calcium; cannabinoid; lateral synaptic potentiation; mitochondria.

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