Differential GABA A receptor clustering determines GABA synapse plasticity in rat oxytocin neurons around parturition and the onset of lactation

Jan-Jurjen Koksma, Jean-Marc Fritschy, Volker MacK, Ronald E. van Kesteren, Arjen B. Brussaard

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Abstract

Expression, functional properties, and clustering of α1-, α2-, and α3-subunit containing GABA A receptors (GABA ARs) were studied in dorsomedial SON neurons of the adult female rat supraoptic nucleus (SON) around parturition. We show that, although the decay time constant (τ decay) 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 τ decay of postsynaptic currents. In α-latrotoxin (α-LTX)-induced bursts of synaptic currents from individual synapses, the τ decay of consecutive synaptic events within bursts was very similar, but between bursts there were large differences in τ decay. This suggested that different synapses within individual SON neurons contain distinct GABA AR subtypes. Using multilabeling confocal microscopy, we examined the distribution of postsynaptic α1-, α2-, and α3-GABA ARs, based on colocalization with gephyrin. We show that the three GABA AR 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-GABA ARs, was significantly increased. Thus, the functional synaptic diversity at the postsynaptic level in dorsomedial SON neurons is correlated with a differential clustering of distinct GABA AR subtypes at individual synapses. © 2004 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)128-140
JournalMolecular and Cellular Neuroscience
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 2005
Externally publishedYes

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