The GABAB1a Isoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses Export

@article{citeulike:4026333, abstract = {GABAB receptor subtypes are based on the subunit isoforms GABAB1a and GABAB1b, which associate with GABAB2 subunits to form pharmacologically indistinguishable GABAB(1a,2) and GABAB(1b,2) receptors. Studies with mice selectively expressing GABAB1a or GABAB1b subunits 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 GABAB1a than GABAB1b protein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations [\≥]1 {micro}M, 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 GABAB receptors. Our data demonstrate that the difference in GABAB1a and GABAB1b protein 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 GABAB1a and GABAB1b proteins is of regulatory relevance. 10.1523/JNEUROSCI.3697-08.2009}, author = {Guetg, Nicole and Seddik, Riad and Vigot, Rejan and Turecek, Rostislav and Gassmann, Martin and Vogt, Kaspar E. and Brauner-Osborne, Hans and Shigemoto, Ryuichi and Kretz, Oliver and Frotscher, Michael and Kulik, Akos and Bettler, Bernhard}, citeulike-article-id = {4026333}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.3697-08.2009}, citeulike-linkout-1 = {http://www.jneurosci.org/cgi/content/abstract/29/5/1414}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19193888}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19193888}, day = {4}, doi = {10.1523/JNEUROSCI.3697-08.2009}, journal = {J. Neurosci.}, keywords = {100209, gaba\_receptors, hetero\_plasticity, synaptic\_plasticity}, month = {February}, number = {5}, pages = {1414--1423}, posted-at = {2009-02-09 19:30:38}, priority = {2}, title = {The GABAB1a Isoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses}, url = {http://dx.doi.org/10.1523/JNEUROSCI.3697-08.2009}, volume = {29}, year = {2009} }

TY - JOUR ID - citeulike:4026333 L3 - citeulike-article-id:4026333 N2 - GABAB receptor subtypes are based on the subunit isoforms GABAB1a and GABAB1b, which associate with GABAB2 subunits to form pharmacologically indistinguishable GABAB(1a,2) and GABAB(1b,2) receptors. Studies with mice selectively expressing GABAB1a or GABAB1b subunits 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 GABAB1a than GABAB1b protein is present at presynaptic sites, consistent with the findings at other glutamatergic synapses. In the presence of baclofen at concentrations [≥]1 {micro}M, 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 GABAB receptors. Our data demonstrate that the difference in GABAB1a and GABAB1b protein 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 GABAB1a and GABAB1b proteins is of regulatory relevance. 10.1523/JNEUROSCI.3697-08.2009 IS - 5 JF - J. Neurosci. EP - 1423 TI - The GABAB1a Isoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses VL - 29 SP - 1414 KW - 100209 KW - gaba_receptors KW - hetero_plasticity KW - synaptic_plasticity AU - Guetg, Nicole AU - Seddik, Riad AU - Vigot, Rejan AU - Turecek, Rostislav AU - Gassmann, Martin AU - Vogt, Kaspar AU - Brauner-Osborne, Hans AU - Shigemoto, Ryuichi AU - Kretz, Oliver AU - Frotscher, Michael AU - Kulik, Akos AU - Bettler, Bernhard PY - 2009/02/04/ UR - http://dx.doi.org/10.1523/JNEUROSCI.3697-08.2009 ER -