Neonatal development of the rat visual cortex: synaptic function of GABA_a receptor α subunits

Each GABA(A) receptor consists of two alpha and three other subunits. The spatial and temporal distribution of different alpha subunit isomeres expressed by the CNS is highly regulated. Here we study changes in functional contribution of different alpha subunits during neonatal development in rat visual cortex. First, we characterized postsynaptic alpha subunit expression in layer II-III neurons, using subunit-specific pharmacology combined with electrophysiological recordings in acutely prepared brain slices. This showed clear developmental downregulation of the effects of bretazenil (1 microm) and marked upregulation of the effect of 100 nM of zolpidem on the decay of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the concentrations used we interpret this as downregulation of the synaptic alpha3 and upregulation of alpha1 subunit. Furthermore, the effect of furosemide, being indicative of the functional contribution of alpha4, was increased between postnatal days 6 and 21. Our second aim was to study the effects of plasticity in alpha subunit expression on decay properties of GABAergic IPSCs. We found that bretazenil-sensitive IPSCs have the longest decay time constant in juvenile neurons. In mature neurons, zolpidem- and furosemide-sensitive IPSCs have relatively fast decay kinetics, whereas bretazenil-sensitive IPSCs decay relatively slowly. Analysis of alpha1 deficient mice and alpha1 antisense oligonucleotide deletion in rat explants showed similar results to those obtained by zolpidem application. Thus, distinct alpha subunit contributions create heterogeneity in developmental acceleration of IPSC decay in neocortex.