GABAA receptor subunit immunoreactivity in primate visual cortex: Distribution in macaques and humans and regulation by visual input in adulthood

Abstract

Subunit proteins that make up functional GABAA receptors were localized by immunocytochemistry in the primary visual cortex (area 17) of adult monkeys and humans, Immunoreactivity for the α1, β2/3, and γ2 subunits is greatest in layers (II-III, IVA and IVC) of monkey area 17 that contain the highest density of GABA neurons and terminals. Immunostaining for each subunit is unevenly distributed in layers II and III, where patches of immunoreactivity correspond to regions of intense cytochrome oxidase (CO) staining, and in layer IVA, where intense immunoreactivity forms a honeycomb pattern identical to the CO staining pattern. Immunoreactivity for the subunits is localized principally within the neuropil, which, by simultaneous comparison with the distribution of microtubule-associated protein immunostaining, was found to include bundles of thin dendrites and zones of numerous dendritic segments. In addition, γ2 immunostaining surrounds the somata of a subpopulation of GA-BAergic neurons, immunoreactive for the calcium-binding protein parvalbumin. All three subunits are present in the somata and processes of neurons that occupy the white matter subjacent to monkey area 17. In human visual cortex, the α1, β2/3, and γ2 subunits are distributed in a manner similar to that found in monkeys, with relatively intense immunostaining in layers IVC and IVA. In layer IVC, vertical stripes of intense receptor immunostaining (20-30 μm wide) alternate with wider stripes of pale immunostaining (30-60 μm wide). In the upper and lower halves of IVCβ, these stripes form lattices similar to those in layers IVC and IVA of monkeys. Following monocular deprivation by intravitreal injections of TTX in adult monkeys, immunoreactivity for each subunit in layer IVC consists of alternating intensely and lightly stained stripes. Comparison with the pattern of CO staining indicates that intense immunostaining for α1, β2/3, and γ2 occurs in normal-eye stripes while abnormally light immunostaining is present in deprived-eye stripes. For all three subunits, immunoreactivity in deprived-eye stripes is reduced within 5 d of monocular deprivation and remains abnormally low for deprivations that extend to at least 30 d. These findings indicate that each of several GABAA receptor subunits adopt similar laminar and compartmental distributions in monkey and human area 17 and are likely to be expressed by the same neurons. The deprivation-dependent reduction in immunoreactivity for α1, β2/3, and γ2 subunits suggests that all are regulated by visually driven activity. Together with the previously observed reduction in GABA immunoreactivity, the downregulation of GABAA receptors would be expected to leave the deprived-eye column with reduced levels of GABA-mediated inhibition, most likely contributing to the functional adaptation seen in visually deprived adult monkeys.