Mice lacking the major adult GABAA receptor subtype have normal number of synapses, but retain juvenile IPSC kinetics until adulthood

There is a large variation in structurally and functionally different GABA(A) receptor subtypes. The expression pattern of GABA(A) receptor subunits is highly regulated, both temporarily and spatially. Especially during development, profound changes in subunit expression have been described. In most brain areas, the GABA(A) receptor alpha 1 subunit replaces the alpha 2 and/or alpha 3 subunit as major alpha subunit. This is accompanied by a marked decrease in the open time of GABA(A) receptors and hence in the duration of postsynaptic responses. We describe here the development of GABAergic, synaptic transmission in mice lacking the alpha 1 subunit. We show that alpha 1 is to a large extent-but not entirely-responsible for the relatively short duration of postsynaptic responses in the developing and the mature brain. However, alpha 1 already affects GABAergic transmission in the neonatal cerebral cortex when it is only sparsely expressed. It appears that the alpha 1 -/- mice do not show a large reduction in GABAergic synapses but do retain long-lasting postsynaptic currents into adulthood. Hence, they form a good model to study the functional role of developmental GABA(A) receptor subunit switching.