Thalamic ventrobasal (VB) relay neurones express multiple GABAA receptor subtypes mediating phasic and tonic inhibition. During postnatal development, marked changes in subunit expression occur, presumably reflecting changes in functional properties of neuronal networks. The aims of this study were to characterize the properties of synaptic and extrasynaptic GABAA receptors of developing VB neurones and investigate the role of the α 1 subunit during maturation of GABA-ergic transmission, using electrophysiology and immunohistochemistry in wild type (WT) and α1 0/0 mice and mice engineered to express diazepam-insensitive receptors (α1H101R, α2H101R). In immature brain, rapid (P8/9-P10/11) developmental change to mIPSC kinetics and increased expression of extrasynaptic receptors (P8-27) formed by the α4 and δ subunit occurred independently of the α1 subunit. Subsequently (≥ P15), synaptic α2 subunit/gephyrin clusters of WT VB neurones were replaced by those containing the α1 subunit. Surprisingly, in α1 0/0 VB neurones the frequency of mIPSCs decreased between P12 and P27, because the α2 subunit also disappeared from these cells. The loss of synaptic GABAA receptors led to a delayed disruption of gephyrin clusters. Despite these alterations, GABA-ergic terminals were preserved, perhaps maintaining tonic inhibition. These results demonstrate that maturation of synaptic and extrasynaptic GABAA receptors in VB follows a developmental programme independent of the α1 subunit. Changes to synaptic GABAA receptor function and the increased expression of extrasynaptic GABAA receptors represent two distinct mechanisms for fine-tuning GABA-ergic control of thalamic relay neurone activity during development.
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Developmental maturation of synaptic and extrasynaptic GABAA receptors in mouse thalamic ventrobasal neurones. / Peden, Dianne R.; Petitjean, Caroline M.; Herd, Murray B.; Durakoglugil, Murat S.; Rosahl, Thomas W.; Wafford, Keith; Homanics, Gregg E.; Belelli, Delia; Fritschy, Jean Marc; Lambert, Jeremy J.In: Journal of Physiology, Vol. 586, No. 4, 15.02.2008, p. 965-987.
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