Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Feb 19;81(4):728-39.
doi: 10.1016/j.neuron.2014.02.007.

Gliotransmitters travel in time and space

Alfonso Araque  1 , Giorgio Carmignoto  2 , Philip G Haydon  3 , Stéphane H R Oliet  4 , Richard Robitaille  5 , Andrea Volterra  6
Affiliations
Review

Gliotransmitters travel in time and space

Alfonso Araque et al. Neuron. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Bidirectional Neuron-astrocyte Communication Granted by High Affinity, Slowly Desensitizing Receptors
(A) Schematic drawing of the tripartite synapse illustrating the location of low and high affinity ligand receptors. (B) Neurotransmitters rapidly activate low affinity receptors at the postsynaptic neuronal membrane and diffuse outside the synaptic cleft to activate high affinity receptors at the astrocytic membrane. (C) Gliotransmitters activate high affinity receptors at perisynaptic locations in the neuronal membrane. Neurotransmitter (B) or gliotransmitter (C) decreasing concentrations over distance from release sites is illustrated by different color intensity.
Figure 2
Figure 2. Synaptic Modulatory Actions of Gliotransmitters Depend on Integration by Astrocytes of the Ca2+ Changes Evoked by Different Levels of Neuronal Activity
(A) Low levels of synaptic activity (blue arrow, left) evoke rapid, spatially restricted Ca2+ elevations at an astrocytic process (red trace) resulting in a gliotransmitter release that locally modulates synaptic transmission (green arrow, right) (Jourdain et al., 2007; Perea and Araque, 2007; Pascual et al., 2012; Santello et al., 2011; Panatier et al., 2011). The change in synaptic efficacy due to gliotransmitter-mediated regulation of the probability of release is illustrated as an increase in the mean amplitude of excitatory postsynaptic events(dashed and solid blue line). (B) Ca2+ elevations evoked at an astrocytic process by an intense activity of an individual synapse diffuse to a nearby process (red arrow) to trigger gliotransmitter release that affects nearby synapses (right). The red superimposed traces are the integrated Ca2+ response (solid line) and the elementary Ca2+ response (dashed line, same as solid line in A). As a result of this astrocyte modulatory action, synaptic transmission (solid blue line) can be either potentiated (Navarrete and Araque, 2010) or depressed (Zhang et al., 2003; Pascual et al., 2005; Andersson et al., 2007; Serrano et al., 2006)(dashed blue line in a and b, respectively). As in (C), the focus of the phenomenon being described is indicated in colour, while the elements that are not the focus are greyed out (but are not necessarily inactive). (C) Multiple Ca2+ events at different processes evoked by simultaneously active synapses are spatially and temporally integrated (left) resulting in a global, long lasting Ca2+ elevation that can affect synaptic transmission in the territory of individual astrocytes (right) (Henneberger et al., 2010). The global Ca2+ response (solid line) and the integrated Ca2+ response (dashed line, same as solid line in B) are reported. Note the different time scale of Ca2+ traces in (A), (B) and (C).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Agulhon C, Fiacco TA, McCarthy KD. Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science. 2010;327:1250–1254. - PubMed
    1. Andersson M, Blomstrand F, Hanse E. Astrocytes play a critical role in transient heterosynaptic depression in the rat hippocampal CA1 region. J Physiol. 2007;585:843–852. - PMC - PubMed
    1. Angulo MC, Kozlov AS, Charpak S, Audinat E. Glutamate released from glial cells synchronizes neuronal activity in the hippocampus. J Neurosci. 2004;24:6920–6927. - PMC - PubMed
    1. Araque A, Martín ED, Perea G, Arellano JI, Buño W. Synaptically released acetylcholine evokes Ca2+ elevations in astrocytes in hippocampal slices. J Neurosci. 2002;22:2443–2450. - PMC - PubMed
    1. Araque A, Parpura V, Sanzgiri RP, Haydon PG. Glutamate-dependent astrocyte modulation of synaptic transmission between cultured hippocampal neurons. Eur J Neurosci. 1998a;10:2129–2142. - PubMed

Publication types

LinkOut - more resources