The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses. / Guetg, Nicole; Seddik, Riad; Vigot, Réjan; Turecek, Rostislav; Gassmann, Martin; Vogt, Kaspar E; Bräuner-Osborne, Hans; Shigemoto, Ryuichi; Kretz, Oliver; Frotscher, Michael; Kulik, Ákos; Bettler, Bernhard.

In: Journal of Neuroscience, Vol. 29, No. 5, 2009, p. 1414-1423.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Guetg, N, Seddik, R, Vigot, R, Turecek, R, Gassmann, M, Vogt, KE, Bräuner-Osborne, H, Shigemoto, R, Kretz, O, Frotscher, M, Kulik, Á & Bettler, B 2009, 'The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses', Journal of Neuroscience, vol. 29, no. 5, pp. 1414-1423. https://doi.org/10.1523/JNEUROSCI.3697-08.2009

APA

Guetg, N., Seddik, R., Vigot, R., Turecek, R., Gassmann, M., Vogt, K. E., ... Bettler, B. (2009). The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses. Journal of Neuroscience, 29(5), 1414-1423. https://doi.org/10.1523/JNEUROSCI.3697-08.2009

Vancouver

Guetg N, Seddik R, Vigot R, Turecek R, Gassmann M, Vogt KE et al. The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses. Journal of Neuroscience. 2009;29(5):1414-1423. https://doi.org/10.1523/JNEUROSCI.3697-08.2009

Author

Guetg, Nicole ; Seddik, Riad ; Vigot, Réjan ; Turecek, Rostislav ; Gassmann, Martin ; Vogt, Kaspar E ; Bräuner-Osborne, Hans ; Shigemoto, Ryuichi ; Kretz, Oliver ; Frotscher, Michael ; Kulik, Ákos ; Bettler, Bernhard. / The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 5. pp. 1414-1423.

Bibtex

@article{3c68ded0f76b11ddbf70000ea68e967b,
title = "The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses",
abstract = "GABA(B) receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which associate with GABA(B2) subunits to form pharmacologically indistinguishable GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Studies with mice selectively expressing GABA(B1a) or GABA(B1b) subunits revealed that GABA(B(1a,2)) receptors are more abundant than GABA(B(1b,2)) receptors at glutamatergic terminals. Accordingly, it was found that GABA(B(1a,2)) receptors are more efficient than GABA(B(1b,2)) receptors in inhibiting glutamate release when maximally activated by exogenous application of the agonist baclofen. Here, we used a combination of genetic, ultrastructural and electrophysiological approaches to analyze to what extent GABA(B(1a,2)) and GABA(B(1b,2)) receptors inhibit glutamate release in response to physiological activation. We first show that at hippocampal mossy fiber (MF)-CA3 pyramidal neuron synapses more GABA(B1a) than GABA(B1b) protein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations >or=1 microm, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors contribute to presynaptic inhibition of glutamate release. However, at lower concentrations of baclofen, selectively GABA(B(1a,2)) receptors contribute to presynaptic inhibition. Remarkably, exclusively GABA(B(1a,2)) receptors inhibit glutamate release in response to synaptically released GABA. Specifically, we demonstrate that selectively GABA(B(1a,2)) receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABA(B) receptors. Our data demonstrate that the difference in GABA(B1a) and GABA(B1b) protein levels at MF terminals is sufficient to produce a strictly GABA(B1a)-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABA(B1a) and GABA(B1b) proteins is of regulatory relevance.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Nicole Guetg and Riad Seddik and R{\'e}jan Vigot and Rostislav Turecek and Martin Gassmann and Vogt, {Kaspar E} and Hans Br{\"a}uner-Osborne and Ryuichi Shigemoto and Oliver Kretz and Michael Frotscher and {\'A}kos Kulik and Bernhard Bettler",
note = "Keywords: GABA(B); GABA-B; metabotropic; hippocampus; presynaptic inhibition; heteroreceptor",
year = "2009",
doi = "10.1523/JNEUROSCI.3697-08.2009",
language = "English",
volume = "29",
pages = "1414--1423",
journal = "The Journal of neuroscience : the official journal of the Society for Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "5",

}

RIS

TY - JOUR

T1 - The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses

AU - Guetg, Nicole

AU - Seddik, Riad

AU - Vigot, Réjan

AU - Turecek, Rostislav

AU - Gassmann, Martin

AU - Vogt, Kaspar E

AU - Bräuner-Osborne, Hans

AU - Shigemoto, Ryuichi

AU - Kretz, Oliver

AU - Frotscher, Michael

AU - Kulik, Ákos

AU - Bettler, Bernhard

N1 - Keywords: GABA(B); GABA-B; metabotropic; hippocampus; presynaptic inhibition; heteroreceptor

PY - 2009

Y1 - 2009

N2 - GABA(B) receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which associate with GABA(B2) subunits to form pharmacologically indistinguishable GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Studies with mice selectively expressing GABA(B1a) or GABA(B1b) subunits revealed that GABA(B(1a,2)) receptors are more abundant than GABA(B(1b,2)) receptors at glutamatergic terminals. Accordingly, it was found that GABA(B(1a,2)) receptors are more efficient than GABA(B(1b,2)) receptors in inhibiting glutamate release when maximally activated by exogenous application of the agonist baclofen. Here, we used a combination of genetic, ultrastructural and electrophysiological approaches to analyze to what extent GABA(B(1a,2)) and GABA(B(1b,2)) receptors inhibit glutamate release in response to physiological activation. We first show that at hippocampal mossy fiber (MF)-CA3 pyramidal neuron synapses more GABA(B1a) than GABA(B1b) protein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations >or=1 microm, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors contribute to presynaptic inhibition of glutamate release. However, at lower concentrations of baclofen, selectively GABA(B(1a,2)) receptors contribute to presynaptic inhibition. Remarkably, exclusively GABA(B(1a,2)) receptors inhibit glutamate release in response to synaptically released GABA. Specifically, we demonstrate that selectively GABA(B(1a,2)) receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABA(B) receptors. Our data demonstrate that the difference in GABA(B1a) and GABA(B1b) protein levels at MF terminals is sufficient to produce a strictly GABA(B1a)-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABA(B1a) and GABA(B1b) proteins is of regulatory relevance.

AB - GABA(B) receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which associate with GABA(B2) subunits to form pharmacologically indistinguishable GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Studies with mice selectively expressing GABA(B1a) or GABA(B1b) subunits revealed that GABA(B(1a,2)) receptors are more abundant than GABA(B(1b,2)) receptors at glutamatergic terminals. Accordingly, it was found that GABA(B(1a,2)) receptors are more efficient than GABA(B(1b,2)) receptors in inhibiting glutamate release when maximally activated by exogenous application of the agonist baclofen. Here, we used a combination of genetic, ultrastructural and electrophysiological approaches to analyze to what extent GABA(B(1a,2)) and GABA(B(1b,2)) receptors inhibit glutamate release in response to physiological activation. We first show that at hippocampal mossy fiber (MF)-CA3 pyramidal neuron synapses more GABA(B1a) than GABA(B1b) protein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations >or=1 microm, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors contribute to presynaptic inhibition of glutamate release. However, at lower concentrations of baclofen, selectively GABA(B(1a,2)) receptors contribute to presynaptic inhibition. Remarkably, exclusively GABA(B(1a,2)) receptors inhibit glutamate release in response to synaptically released GABA. Specifically, we demonstrate that selectively GABA(B(1a,2)) receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABA(B) receptors. Our data demonstrate that the difference in GABA(B1a) and GABA(B1b) protein levels at MF terminals is sufficient to produce a strictly GABA(B1a)-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABA(B1a) and GABA(B1b) proteins is of regulatory relevance.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1523/JNEUROSCI.3697-08.2009

DO - 10.1523/JNEUROSCI.3697-08.2009

M3 - Journal article

C2 - 19193888

VL - 29

SP - 1414

EP - 1423

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 5

ER -

ID: 10247339