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

¹Departments of Experimental Neurophysiology and ²Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Submitted 24 January 2005; accepted in final form 6 March 2005

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 1 subunit replaces the 2 and/or 3 subunit as major 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 1 subunit. We show that 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, 1 already affects GABAergic transmission in the neonatal cerebral cortex when it is only sparsely expressed. It appears that the 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.

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