Developmental maturation of synaptic and extrasynaptic GABAAreceptors in mouse thalamic ventrobasal neurones

Publisher Website
Google Scholar
Abstract
Thalamic ventrobasal (VB) relay neurones express multiple GABAAreceptor 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 GABAAreceptors of developing VB neurones and investigate the role of the α1subunit during maturation of GABA‐ergic transmission, using electrophysiology and immunohistochemistry in wild type (WT) and α10/0mice 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 α4and δ subunit occurred independently of the α1subunit. Subsequently (≥ P15), synaptic α2subunit/gephyrin clusters of WT VB neurones were replaced by those containing the α1subunit. Surprisingly, in α10/0VB neurones the frequency of mIPSCs decreased between P12 and P27, because the α2subunit also disappeared from these cells. The loss of synaptic GABAAreceptors 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 GABAAreceptors in VB follows a developmental programme independent of the α1subunit. Changes to synaptic GABAAreceptor function and the increased expression of extrasynaptic GABAAreceptors represent two distinct mechanisms for fine‐tuning GABA‐ergic control of thalamic relay neurone activity during development.

This publication has 57 references indexed in Scilit: