An autocrine purinergic signaling controls astrocyte-induced neuronal excitation.
Fiche publication
Date publication
septembre 2017
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PFRIEGER Frank
Tous les auteurs :
Shen W, Nikolic L, Meunier C, Pfrieger F, Audinat E
Lien Pubmed
Résumé
Astrocyte-derived gliotransmitters glutamate and ATP modulate neuronal activity. It remains unclear, however, how astrocytes control the release and coordinate the actions of these gliotransmitters. Using transgenic expression of the light-sensitive channelrhodopsin 2 (ChR2) in astrocytes, we observed that photostimulation reliably increases action potential firing of hippocampal pyramidal neurons. This excitation relies primarily on a calcium-dependent glutamate release by astrocytes that activates neuronal extra-synaptic NMDA receptors. Remarkably, our results show that ChR2-induced Ca increase and subsequent glutamate release are amplified by ATP/ADP-mediated autocrine activation of P2Y1 receptors on astrocytes. Thus, neuronal excitation is promoted by a synergistic action of glutamatergic and autocrine purinergic signaling in astrocytes. This new mechanism may be particularly relevant for pathological conditions in which ATP extracellular concentration is increased and acts as a major danger signal.
Mots clés
Action Potentials, Adenosine Triphosphate, metabolism, Animals, Astrocytes, metabolism, Autocrine Communication, Calcium, metabolism, Calcium Signaling, Cell Communication, Female, Male, Mice, Neurons, metabolism, Purinergic Agents, metabolism, Receptors, N-Methyl-D-Aspartate, metabolism, Receptors, Purinergic, metabolism, Signal Transduction
Référence
Sci Rep. 2017 09 12;7(1):11280