Ontogeny of GABAA/benzodiazepine receptor subunit mRNAs in the murine inferior olive: transient appearance of beta 3 subunit mRNA and [3H]muscimol binding sites.
The GABAA/benzodiazepine receptor consists of at least four subunits, alpha, beta, gamma and delta, each comprised of several variants. The developmental expression of the alpha 1, beta 1-3, gamma 2 and delta subunits was studied in the murine inferior olivary nucleus by in situ hybridization with antisense cRNA probes. The postnatal appearance and distribution of [3H]flunitrazepam and [3H]muscimol binding sites, alpha and beta subunit-specific ligands respectively, were also studied autoradiographically. The beta 3 subunit was transiently expressed in each of the subnuclei of the inferior olive: The signal was strong at birth, increased throughout postnatal week 1 and rapidly declined thereafter to low adult levels. A similar pattern of labeling was observed with [3H]muscimol. Detectable levels of alpha 1 subunit mRNA hybridization signal and [3H]flunitrazepam binding sites were also present in the inferior olive at birth, decreasing thereafter. Low to moderate levels of beta 1, beta 2, and gamma 2 subunit mRNAs were present in olivary neurons throughout postnatal development, while delta mRNAs were largely absent. It has been reported previously that, during the 2nd postnatal week, the ratio of climbing fiber terminals to Purkinje cells is reduced from 3:1, as observed in neonates, to the 1:1 relationship observed in the adult cerebellar cortex. Our results raise the possibility that the subunit composition of the GABAA/benzodiazepine receptor in inferior olivary neurons undergoes changes during development, and that this process may be related to the elimination of multiple climbing fiber innervation of cerebellar Purkinje cells.
Frostholm
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A
Department of Pharmacology, Ohio State University, Columbus 43210.
Zdilar
D
D
Luntz-Leybman
V
V
Janapati
V
V
Rotter
A
A
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D005445:Flunitrazepam / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009118:Muscimol / Q000378:metabolism*; D009847:Olivary Nucleus / Q000254:growth & development / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics*; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic; D014316:Tritium
D010446:Peptide Fragments; D015347:RNA Probes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C079942:flunitrazepam receptor; D014316:Tritium; D009118:Muscimol; D005445:Flunitrazepam