COINCIDENTAL APPEARANCE OF THE ALPHA-1-SUBUNIT OF THE GABA-A-RECEPTORAND THE TYPE-I BENZODIAZEPINE RECEPTOR NEAR BIRTH IN MACAQUE MONKEY VISUAL-CORTEX

The expression of subtypes of the GABA-A/benzodiazepine receptor compl ex has been studied during pre- and postnatal development of Macaca mo nkey visual cortex using complementary radioligand and immunocytochemi cal labeling. Type I benzodiazepine receptors were labeled directly by [H-3]zolpidem. Type II receptors were determined by the amount of bin ding for [H-3]flunitrazepam (FZ) persisting in the presence of the typ e I-specific ligand CL218872. Monoclonal antibody bd24 was used to lab el alpha 1 subunits and bd17 to label beta 2 and beta 3 subunits of th e 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 som ewhat into adulthood. Neither radioligand labeling for type I receptor s nor immunocytochemical staining for the alpha 1 subunit were apparen t until mid-gestation. Both markers appeared shortly before birth in l ayer 4C, and then in other cortical layers after birth. Immunoreactivi ty for the alpha 1 subunit increased steadily after birth until it bec ame more intense than that for beta 2/3 subunits in the adult. Quantit ative densitometry of CL218872 competition for [H-3]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 criti cal period for geniculostriate development, suggesting that the change from type II to type I receptors and the appearance of alpha 1 subuni ts 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.