The identification of the presence of active signaling between astrocytes and neurons in a process termed gliotransmission has caused a paradigm shift in our thinking about brain function. However, we are still in the early days of the conceptualization of how astrocytes influence synapses, neurons, networks, and ultimately behavior. In this Perspective, our goal is to identify emerging principles governing gliotransmission and consider the specific properties of this process that endow the astrocyte with unique functions in brain signal integration. We develop and present hypotheses aimed at reconciling confounding reports and define open questions to provide a conceptual framework for future studies. We propose that astrocytes mainly signal through high-affinity slowly desensitizing receptors to modulate neurons and perform integration in spatiotemporal domains complementary to those of neurons.
Bibliographical noteFunding Information:
For the kind hospitality, the authors would like to thank Francesco Pasti and La Frassina, in the quiet countryside near Venice, where we met to discuss and write the main body of this manuscript. We also thank Micaela Zonta for her support in the preparation of figures, and Paulo Magalhães for critical reading of the manuscript. The original work by the authors was supported by the following grants: MINECO (BFU2010-15832; CSD2010-00045) and Cajal Blue Brain (A.A.); European Union HEALTH-F2-2007-202167 (A.A. and G.C.); Telethon Italy GGP10138B/GGP12265, Cariparo Foundation, and FIRB RBAP11X42L (G.C.); National Institutes of Health R01NS037585, R01AA020183, and R01MH095385 (P.G.H.); INSERM, Conseil Régional d’Aquitaine, Équipe FRM, and the Labex BRAIN (S.H.R.O.); Canadian Institute of Health Research (MOP-14137 and MOP-111070), a Discovery group grant from the National Science and Engineering Research Council (RGPGP 203729), and a group infrastructure grant from Fonds de recherche du Québec-Santé (R.R.); ERC Advanced, grant 340368 “Astromnesis,” Swiss National Science Foundation, grant 31003A-140999, and National Centres of Competence in Research (NCCR) “Synapsy” and “Transcure” (A.V.). P.G.H. is cofounder and President of GliaCure, Inc.