Astroglial metabolic networks sustain hippocampal synaptic transmission.
Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.
Rouach
Nathalie
N
INSERM U840, Collége de France, 11 place Marcelin Berthelot, 75005 Paris, France. nathalie.rouach@college-de-france.fr
Koulakoff
Annette
A
Abudara
Veronica
V
Willecke
Klaus
K
Giaume
Christian
C
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002463:Cell Membrane Permeability; D000075302:Connexin 30; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D004058:Diffusion; D004827:Epilepsy / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials; D017629:Gap Junctions / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism; D009435:Synaptic Transmission
D001786:Blood Glucose; D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C100629:Gjb6 protein, mouse; D018091:Receptors, AMPA; D019344:Lactic Acid; D018698:Glutamic Acid; D005947:Glucose