Astrocytic GABA transporter activity modulates excitatory neurotransmission
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Astrocytic GABA transporter activity modulates excitatory neurotransmission. / Boddum, Kim; Jensen, Thomas P.; Magloire, Vincent; Kristiansen, Uffe; Rusakov, Dmitri A; Pavlov, Ivan; Walker, Matthew C.
In: Nature Communications, Vol. 7, 13572, 25.11.2016.Research output: Contribution to journal › Journal article › Research › peer-review
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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.
U2 - 10.1038/ncomms13572
DO - 10.1038/ncomms13572
M3 - Journal article
C2 - 27886179
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 13572
ER -
ID: 169361154