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.
Department of Biological Structure, University of Washington, Seattle 98195.
A
A
Hendrickson
D
D
March
G
G
Richards
A
A
Erickson
C
C
Shaw
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