Astrocytic GABA transporter activity modulates excitatory neurotransmission

Kim Boddum; Thomas P. Jensen; Vincent Magloire; Uffe Kristiansen; Dmitri A Rusakov; Ivan Pavlov; Matthew C Walker

doi:10.1038/ncomms13572

Astrocytic GABA transporter activity modulates excitatory neurotransmission

Kim Boddum, Thomas P. Jensen, Vincent Magloire, Uffe Kristiansen, Dmitri A Rusakov, Ivan Pavlov, Matthew C Walker

Department of Drug Design and Pharmacology

66 Citations (Scopus)

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Abstract

Astrocytes 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 Ca(2+) through Na(+)/Ca(2+) 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.

Original language	English
Article number	13572
Journal	Nature Communications
Volume	7
Number of pages	10
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms13572
Publication status	Published - 25 Nov 2016

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Astrocytic GABA transporter activity modulates excitatory neurotransmissionFinal published version, 1.37 MBLicence: CC BY

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title = "Astrocytic GABA transporter activity modulates excitatory neurotransmission",

abstract = "Astrocytes 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 Ca(2+) through Na(+)/Ca(2+) 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.",

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T1 - Astrocytic GABA transporter activity modulates excitatory neurotransmission

AU - Boddum, Kim

AU - Jensen, Thomas P.

AU - Magloire, Vincent

AU - Kristiansen, Uffe

AU - Rusakov, Dmitri A

AU - Pavlov, Ivan

AU - Walker, Matthew C

PY - 2016/11/25

Y1 - 2016/11/25

N2 - Astrocytes 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 Ca(2+) through Na(+)/Ca(2+) 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.

AB - Astrocytes 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 Ca(2+) through Na(+)/Ca(2+) 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.

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DO - 10.1038/ncomms13572

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SN - 2041-1723

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JO - Nature Communications

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Astrocytic GABA transporter activity modulates excitatory neurotransmission

Abstract

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