突触可塑性
细胞生物学
生物
钙信号传导
神经科学
内大麻素系统
长时程增强
神经传递
线粒体
星形胶质细胞
内质网
受体
信号转导
生物化学
中枢神经系统
作者
Roman Serrat,Ana Covelo,Vladimir Kouskoff,Sebastien Delcasso,Andrea Ruiz-Calvo,Nicolas Chenouard,Carol Stella,Corinne Blancard,Bénédicte Salin,Francisca Julio-Kalajzić,Astrid Cannich,Federico Massa,Marjorie Varilh,Severine Deforges,Laurie M. Robin,Diego De Stefani,Arnau Busquets-Garcia,Frédéric Gambino,Anna Beyeler,Sandrine Pouvreau,Giovanni Marsicano
出处
期刊:Cell Reports
[Elsevier]
日期:2021-12-01
卷期号:37 (12): 110133-110133
被引量:13
标识
DOI:10.1016/j.celrep.2021.110133
摘要
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.
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