title: Differential GABAA receptor clustering determines GABA synapse plasticity in rat oxytocin neurons around parturition and the onset of lactation.
abstract: Expression, functional properties, and clustering of alpha 1-, alpha 2-, and alpha 3-subunit containing GABA(A) receptors (GABA(A)Rs) were studied in dorsomedial SON neurons of the adult female rat supraoptic nucleus (SON) around parturition. We show that, although the decay time constant (tau(decay)) of GABAergic postsynaptic currents between and within individual recordings was very diverse, ranging from fast (i.e., alpha 1-like) to significantly slower (i.e., non-alpha 1-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 alpha 1, alpha 2, and alpha 3 remained the same before and after parturition. Also, changes in phosphorylation levels are not likely to affect the tau(decay) of postsynaptic currents. In alpha-latrotoxin (alpha-LTX)-induced bursts of synaptic currents from individual synapses, the tau(decay) of consecutive synaptic events within bursts was very similar, but between bursts there were large differences in tau(decay). This suggested that different synapses within individual SON neurons contain distinct GABA(A)R subtypes. Using multilabeling confocal microscopy, we examined the distribution of postsynaptic alpha 1-, alpha 2-, and alpha 3-GABA(A)Rs, based on colocalization with gephyrin. We show that the three GABA(A)R 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 alpha 2- (or alpha 3-), but not alpha1-GABA(A)Rs, 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(A)R subtypes at individual synapses.
authors.affiliation: Department of Experimental Neurophysiology, Centre for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
authors.forename: Jan-Jurjen
authors.initials: JJ
authors.lastname: Koksma
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Fritschy
authors.forename: Volker
authors.initials: V
authors.lastname: Mack
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Van Kesteren
authors.forename: Arjen B
authors.initials: AB
authors.lastname: Brussaard
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007774:Lactation / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D036801:Parturition / Q000502:physiology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011940:Receptor Aggregation / Q000502:physiology*; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D013111:Spider Venoms / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D013111:Spider Venoms; C073441:gephyrin; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; C020763:alpha-latrotoxin