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Journal of Neuroscience, Vol 12, 4151-4172, Copyright © 1992 by Society for Neuroscience
The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development
DJ Laurie, W Wisden and PH Seeburg
Laboratory of Molecular Neuroendocrinology, Center for Molecular Biology, University of Heidelberg, Germany.
The embryonic and postnatal expression of 13 GABAA receptor subunit genes
in the rat CNS was studied by in situ hybridization. Each transcript
exhibited a unique regional and temporal developmental expression profile.
For example, in both embryonic and early postnatal cortex and thalamus,
expression of the alpha 2, alpha 3, alpha 5, and beta 3 mRNAs was
pronounced. In particular, the alpha 5 gene expression underwent a
prominent peak in early brain. Subsequently, the thalamocortical expression
of these four genes substantially diminished and was superseded in the
adult by the alpha 1, alpha 4, beta 2, and delta subunit mRNAs. Similarly,
gamma 1 and gamma 3 gene expression also dropped markedly during
development, their initial stronger expression being restricted to
relatively few structures. In contrast, gamma 2 gene expression was
widespread and mostly remained constant with increasing age. The medial
septum and globus pallidus were regions expressing few subunits in both
early postnatal and adult stages, allowing clear developmental
combinatorial changes to be inferred (alpha 2/alpha 3 beta 2 gamma 2 to
alpha 1 beta 2 gamma 2, alpha 2/alpha 3 beta 2 gamma 1 to alpha 1 beta 2
gamma 1/gamma 2, respectively). In contrast, cerebellar Purkinje cells
exhibited no developmental switch, expressing only the alpha 1, beta 2,
beta 3, and gamma 2 mRNAs from birth to adult. Certain GABAA transcripts
were also detected in germinal zones (e.g., beta 1, beta 3, gamma 1) and in
embryonic peripheral tissues such as dorsal root ganglia (e.g., alpha 2,
alpha 3, beta 3, gamma 2) and intestine (gamma 3). Some parallels in
regional and temporal CNS expression were noted (e.g., alpha 1 beta 2,
alpha 2 beta 3, alpha 4/alpha 6 delta), whereas the alpha 5 and beta 1
regional mRNA expressions converted over time. The changes of GABAA
receptor subunit gene expression suggest a molecular explanation for
earlier observations on changing ligand binding affinities. Thus, the
composition, and presumably properties, of embryonic/early postnatal rat
GABAA receptors differs markedly from those expressed in the adult brain.
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