Mice Lacking the Major Adult GABAA Receptor Subtype Have Normal Number of Synapses, But Retain Juvenile IPSC Kinetics Until Adulthood

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Abstract
There is a large variation in structurally and functionally different GABAA receptor subtypes. The expression pattern of GABAA 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 GABAA receptor α1 subunit replaces the α2 and/or α3 subunit as major α subunit. This is accompanied by a marked decrease in the open time of GABAA 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 GABAA receptor subunit switching.