Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo

The ability of neurons to display more than a single GABA(A)-receptor subtype per cell requires intricate targeting mechanisms. Analysis by confocal laser scanning microscopy revealed that the α2- and α5-subunits differed strikingly in their subcellular distribution in hippocampal pyramidal cells and olfactory bulb granule cells, while the distribution of the γ2-subunit was rather uniform. In mutant mice lacking the α5-subunit gene due to a chromosomal deletion, the absence of the α5-subunit was accompanied by a corresponding decrease of the γ2-subunit immunoreactivity. In striking contrast, the subcellular distribution of the α2-subunit was unchanged in these mutant mice. These findings indicate that the assembly of distinct GABA(A)-receptor subtypes in the same neuron is regulated independently. Furthermore, the α-subunit is a prime candidate for providing domains which direct subcellular targeting.