The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses.
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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, Akos; Bettler, Bernhard.
in: J NEUROSCI, Jahrgang 29, Nr. 5, 5, 2009, S. 1414-1423.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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, Akos
AU - Bettler, Bernhard
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 - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Knockout
KW - Long-Term Synaptic Depression physiology
KW - Mossy Fibers, Hippocampal chemistry
KW - Protein Isoforms physiology
KW - Receptors, GABA-B physiology
KW - Synaptic Transmission physiology
KW - Animals
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Knockout
KW - Long-Term Synaptic Depression physiology
KW - Mossy Fibers, Hippocampal chemistry
KW - Protein Isoforms physiology
KW - Receptors, GABA-B physiology
KW - Synaptic Transmission physiology
M3 - SCORING: Zeitschriftenaufsatz
VL - 29
SP - 1414
EP - 1423
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 5
M1 - 5
ER -
