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Nature Research, Nature Communications, 1(7), 2016

DOI: 10.1038/ncomms13572

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Astrocytic GABA transporter activity modulates excitatory neurotransmission

Journal article published in 2016 by Kim Boddum, Thomas P. Jensen, Vincent Magloire, Uffe Kristiansen ORCID, Dmitri A. Rusakov ORCID, Ivan Pavlov ORCID, Matthew C. Walker ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractAstrocytes are ideally placed to detect and respond to network activity. They express ionotropic and metabotropic receptors, and can release gliotransmitters. Astrocytes also express transporters that regulate the extracellular concentration of neurotransmitters. Here we report a previously unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na+ concentrations and a consequent increase in astrocytic Ca2+ through Na+/Ca2+ exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal glutamate release via activation of presynaptic adenosine receptors. Through this mechanism, increases in astrocytic GAT-3 activity due to GABA released from interneurons contribute to 'diffuse' heterosynaptic depression. This provides a mechanism for homeostatic regulation of excitatory transmission in the hippocampus.