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Abstract: Expression, functional properties, and clustering of α1-, α2-, and α3-subunit containing GABAA receptors (GABAARs) were studied in dorsomedial SON neurons of the adult female rat supraoptic nucleus (SON) around parturition. We show that, although the decay time constant (τdecay) of GABAergic postsynaptic currents between and within individual recordings was very diverse, ranging from fast (i.e., α1-like) to significantly slower (i.e., non-α1-like), there was an overall shift towards slower decaying synaptic currents during the onset of lactation. This shift is not due to changes in mRNA expression levels, because real-time quantitative PCR assays indicated that the relative contribution of α1, α2, and α3 remained the same before and after parturition. Also, changes in phosphorylation levels are not likely to affect the τdecay of postsynaptic currents. In α-latrotoxin (α-LTX)-induced bursts of synaptic currents from individual synapses, the τdecay of consecutive synaptic events within bursts was very similar, but between bursts there were large differences in τdecay. This suggested that different synapses within individual SON neurons contain distinct GABAAR subtypes. Using multilabeling confocal microscopy, we examined the distribution of postsynaptic α1-, α2-, and α3-GABAARs, based on colocalization with gephyrin. We show that the three GABAAR subtypes occurred either in segregated clusters of one subtype as well as in mixed clusters of two or possibly even three receptor subtypes. After parturition, the density and proportion of clusters containing α2- (or α3-), but not α1-GABAARs, was significantly increased. Thus, the functional synaptic diversity at the postsynaptic level in dorsomedial SON neurons is correlated with a differential clustering of distinct GABAAR subtypes at individual synapses. [Copyright &y& Elsevier]

Activity-driven delivery of AMPA receptors is proposed to mediate glutamatergic synaptic plasticity, both during development and learning. In hippocampal CA1 principal neurons, such trafficking is primarily mediated by the abundant GluR-A subunit. We now report a study of GluR-Blong, a C-terminal splice variant of the GluR-B subunit. GluR-Blong synaptic delivery is regulated by two forms of activity. Spontaneous synaptic activity-driven GluR-Blong transport maintains one-third of the steady-state AMPA receptor-mediated responses, while GluR-Blong delivery following the induction of LTP is responsible for approximately 50% of the resulting potentiation at the hippocampal CA3 to CA1 synapses at the time of GluR-Blong peak expression—the second postnatal week. Trafficking of GluR-Blong-containing receptors thus mediates a GluR-A-independent form of glutamatergic synaptic plasticity in the juvenile hippocampus. [Copyright &y& Elsevier]

We demonstrate the fundamental importance of glutamate receptor B (GluR-B) containing AMPA receptors in hippocampal function by analyzing mice with conditional GluR-B deficiency in postnatal forebrain principal neurons (GluR-BΔFb). These mice are as adults sufficiently robust to permit comparative cellular, physiological, and behavioral studies. GluR-B loss induced moderate long-term changes in the hippocampus of GluR-BΔFb mice. Parvalbumin-expressing interneurons in the dentate gyrus and the pyramidal cells in CA3 were decreased in number, and neurogenesis in the subgranular zone was diminished. Excitatory synaptic CA3-to-CA1 transmission was reduced, although synaptic excitability, as quantified by the lowered threshold for population spike initiation, was increased compared with control mice. These changes did not alter CA3-to-CA1 long-term potentiation (LTP), which in magnitude was similar to LTP in control mice. The altered hippocampal circuitry, however, affected spatial learning in GluR-BΔFb mice. The primary source for the observed changes is most likely the AMPA receptor-mediated Ca 2+ signaling that appears after GluR-B depletion, because we observed similar alterations in GluR-BΔFb mice in which the expression of Ca 2+-permeable AMPA receptors in principal neurons was induced by postnatal activation of a Q/R-site editing-deficient GluR-B allele. [ABSTRACT FROM AUTHOR]