Coincidental appearance of the alpha 1 subunit of the GABA-A receptor and the type I benzodiazepine receptor near birth in macaque monkey visual cortex.
The expression of subtypes of the GABA-A/benzodiazepine receptor complex has been studied during pre- and postnatal development of Macaca monkey visual cortex using complementary radioligand and immunocytochemical labeling. Type I benzodiazepine receptors were labeled directly by [3H]zolpidem. Type II receptors were determined by the amount of binding for [3H]flunitrazepam (FZ) persisting in the presence of the type I-specific ligand CL218872. Monoclonal antibody bd24 was used to label alpha 1 subunits and bd17 to label beta 2 and beta 3 subunits of the GABA-A receptor. Radioligand binding data and bd17 immunoreactivity indicated that type II benzodiazepine receptors were present by fetal day (Fd) 74 (44% of gestation). Immunoreactivity for the beta 2/beta 3 subunits increased until 3-6 weeks after birth, and then declined somewhat into adulthood. Neither radioligand labeling for type I receptors nor immunocytochemical staining for the alpha 1 subunit were apparent until mid-gestation. Both markers appeared shortly before birth in layer 4C, and then in other cortical layers after birth. Immunoreactivity for the alpha 1 subunit increased steadily after birth until it became more intense than that for beta 2/3 subunits in the adult. Quantitative densitometry of CL218872 competition for [3H]FZ binding showed that type I/II distribution was 22%/78% at Fd103; 42%/58% at Fd131; 67%/33% at 9 months; and 61%/39% in adult visual cortex. This "switch" between benzodiazepine receptor subtypes overlaps the postnatal critical period for geniculostriate development, suggesting that the change from type II to type I receptors and the appearance of alpha 1 subunits may play a decisive role in the maturation of geniculocortical axon terminations and cortical response properties. It remains to be shown whether this "switch" is dependent on functional visual input.
Hendrickson
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Department of Biological Structure, University of Washington, Seattle 98195.
March
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D
Richards
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Erickson
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Shaw
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D000818:Animals; D000831:Animals, Newborn; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal; D001345:Autoradiography; D001667:Binding, Competitive / Q000502:physiology; D005260:Female; D005445:Flunitrazepam / Q000493:pharmacokinetics; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D008024:Ligands; D008254:Macaca nemestrina; D011247:Pregnancy; D011724:Pyridazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D014793:Visual Cortex / Q000254:growth & development* / Q000378:metabolism*; D000077334:Zolpidem
D014151:Anti-Anxiety Agents; D000911:Antibodies, Monoclonal; D006993:Hypnotics and Sedatives; D008024:Ligands; D011724:Pyridazines; D011725:Pyridines; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C021604:CL 218872; D000077334:Zolpidem