The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses
| Autor: | Réjan Vigot, Nicole Guetg, Hans Bräuner-Osborne, Akos Kulik, Kaspar E. Vogt, Bernhard Bettler, Riad Seddik, Ryuichi Shigemoto, Rostislav Turecek, Oliver Kretz, Martin Gassmann, Michael Frotscher |
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| Rok vydání: | 2009 |
| Předmět: |
Mice
Knockout Mice Inbred BALB C General Neuroscience Long-Term Synaptic Depression Glutamate receptor Articles GABAB receptor Neurotransmission Synaptic Transmission Cell biology Glutamatergic chemistry.chemical_compound Mice Metabotropic receptor Baclofen Biochemistry chemistry nervous system Receptors GABA-B Mossy Fibers Hippocampal Animals Protein Isoforms Receptor Hippocampal mossy fiber |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(5) |
| ISSN: | 1529-2401 |
| Popis: | GABABreceptor subtypes are based on the subunit isoforms GABAB1aand GABAB1b, which associate with GABAB2subunits to form pharmacologically indistinguishable GABAB(1a,2)and GABAB(1b,2)receptors. Studies with mice selectively expressing GABAB1aor GABAB1bsubunits revealed that GABAB(1a,2)receptors are more abundant than GABAB(1b,2)receptors at glutamatergic terminals. Accordingly, it was found that GABAB(1a,2)receptors are more efficient than GABAB(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 GABAB(1a,2)and GABAB(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 GABAB1athan GABAB1bprotein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations ≥1 μm, both GABAB(1a,2)and GABAB(1b,2)receptors contribute to presynaptic inhibition of glutamate release. However, at lower concentrations of baclofen, selectively GABAB(1a,2)receptors contribute to presynaptic inhibition. Remarkably, exclusively GABAB(1a,2)receptors inhibit glutamate release in response to synaptically released GABA. Specifically, we demonstrate that selectively GABAB(1a,2)receptors mediate heterosynaptic depression of MF transmission, a physiological phenomenon involving transsynaptic inhibition of glutamate release via presynaptic GABABreceptors. Our data demonstrate that the difference in GABAB1aand GABAB1bprotein levels at MF terminals is sufficient to produce a strictly GABAB1a-specific effect under physiological conditions. This consolidates that the differential subcellular localization of the GABAB1aand GABAB1bproteins is of regulatory relevance. |
| Databáze: | OpenAIRE |
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