Mice lacking the major adult GABA_A 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 α1 subunit replaces the α2 and/or α3 subunit as major α1 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 α1 subunit. We show that α1 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, α1 already affects GABAergic transmission in the neonatal cerebral cortex when it is only sparsely expressed. It appears that the α1 -/- 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.