Gliotransmission: Beyond Black-and-White.

Details

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Version: Final published version
Serval ID
serval:BIB_E858EFC354C1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Gliotransmission: Beyond Black-and-White.
Journal
The Journal of neuroscience
Author(s)
Savtchouk I., Volterra A.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Publication state
Published
Issued date
03/01/2018
Peer-reviewed
Oui
Volume
38
Number
1
Pages
14-25
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
Astrocytes are highly complex cells with many emerging putative roles in brain function. Of these, gliotransmission (active information transfer from glia to neurons) has probably the widest implications on our understanding of how the brain works: do astrocytes really contribute to information processing within the neural circuitry? "Positive evidence" for this stems from work of multiple laboratories reporting many examples of modulatory chemical signaling from astrocytes to neurons in the timeframe of hundreds of milliseconds to several minutes. This signaling involves, but is not limited to, Ca <sup>2+</sup> -dependent vesicular transmitter release, and results in a variety of regulatory effects at synapses in many circuits that are abolished by preventing Ca <sup>2+</sup> elevations or blocking exocytosis selectively in astrocytes. In striking contradiction, methodologically advanced studies by a few laboratories produced "negative evidence," triggering a heated debate on the actual existence and properties of gliotransmission. In this context, a skeptics' camp arose, eager to dismiss the whole positive evidence based on a number of assumptions behind the negative data, such as the following: (1) deleting a single Ca <sup>2+</sup> release pathway (IP3R2) removes all the sources for Ca <sup>2+</sup> -dependent gliotransmission; (2) stimulating a transgenically expressed Gq-GPCR (MrgA1) mimics the physiological Ca <sup>2+</sup> signaling underlying gliotransmitter release; (3) age-dependent downregulation of an endogenous GPCR (mGluR5) questions gliotransmitter release in adulthood; and (4) failure by transcriptome analysis to detect vGluts or canonical synaptic SNAREs in astrocytes proves inexistence/functional irrelevance of vesicular gliotransmitter release. We here discuss how the above assumptions are likely wrong and oversimplistic. In light of the most recent literature, we argue that gliotransmission is a more complex phenomenon than originally thought, possibly consisting of multiple forms and signaling processes, whose correct study and understanding require more sophisticated tools and finer scientific experiments than done until today. Under this perspective, the opposing camps can be reconciled and the field moved forward. Along the path, a more cautious mindset and an attitude to open discussion and mutual respect between opponent laboratories will be good companions.Dual Perspectives Companion Paper: Multiple Lines of Evidence Indicate That Gliotransmission Does Not Occur under Physiological Conditions, by Todd A. Fiacco and Ken D. McCarthy.
Keywords
Animals, Astrocytes/physiology, Calcium Signaling/physiology, Humans, Neuroglia/physiology, Neurons/physiology, Synapses/physiology, Synaptic Transmission/physiology, astrocyte, astrocyte-neuron interactions, calcium, synaptic modulation, vesicular release
Pubmed
Web of science
Open Access
Yes
Create date
22/01/2018 18:13
Last modification date
20/08/2019 17:11
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