Coincidental appearance of the α1 subunit of the gaba-a receptor and the type ibenzodiazepine receptor near birth in macaque monkey visual cortex

Abstract

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 α1 subunits and bd17 to label β2 and β3 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 β2/β3 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 α1 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 α1 subunit increased steadily after birth until it became more intense than that for β23 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 α1 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.