The GABAB1a Isoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses

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