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 alpha 2- and alph a 5-subunits differed strikingly in their subcellular distribution in hippocampal pyramidal cells and olfactory bulb granule cells, while th e distribution of the gamma 2-subunit was rather uniform. In mutant mi ce lacking the alpha 5-subunit gene due to a chromosomal deletion, the absence of the alpha 5-subunit was accompanied by a corresponding dec rease of the gamma 2-subunit immunoreactivity. In striking contrast, t he subcellular distribution of the gamma 2-subunit was unchanged in th ese mutant mice. These findings indicate that the assembly of distinct GABA(A)-receptor subtypes in the same neuron is regulated independent ly. Furthermore, the alpha-subunit is a prime candidate for providing domains which direct subcellular targeting. Published by Elsevier Scie nce Ireland Ltd.