Developmental expression of the GABAA receptor alpha 1 subunit mRNA in the rat brain.
Recent studies have suggested that the GABAA, receptor complex, the site of action of the inhibitory neurotransmitter gamma amino-butyric acid (GABAA) and the anxiolytic benzodiazepines, is heterogeneous. Moreover, its composition may change during development. To better understand the molecular basis of receptor heterogeneity, the levels and distribution of the mRNA encoding the alpha 1 receptor subunit were examined in the developing and adult rat brain with quantitative in situ hybridization histochemistry. Our studies demonstrate that alpha 1 subunit mRNA expression changes during ontogeny. At late embryonic stages and in the first postnatal week, low levels of the mRNA were detected in the cortex, inferior colliculus, and hippocampus. The mRNA levels in these regions increased during the second and third postnatal weeks. Furthermore, a dramatic change in the distribution of the alpha 1 subunit mRNA was seen in the second postnatal week when the message first became detectable in the cerebellar cortex. During subsequent development and in the mature brain, the alpha 1 subunit mRNA was most abundant in the cerebellum, olfactory bulb, and inferior colliculus, although the absolute levels of mRNA varied by as much as sixfold in selected brain regions. The mature distribution of alpha 1 subunit mRNA, along with its temporal appearance in the cerebellum, suggests that this subunit is a constituent of the Type 1 benzodiazepine site of the GABAA receptor complex. Furthermore, the onset of alpha 1 subunit mRNA expression in the cerebellar cortex coincides with a period of extensive synapse formation, raising the possibility that synaptic interactions modulate the appearance of this GABAA receptor subunit in the cerebellum.
Gambarana
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Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106.
Pittman
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Siegel
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D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism; D012333:RNA, Messenger / Q000145:classification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution
D012333:RNA, Messenger; D011963:Receptors, GABA-A