GABA(A) RECEPTOR SUBUNIT IMMUNOREACTIVITY IN PRIMATE VISUAL-CORTEX - DISTRIBUTION IN MACAQUES AND HUMANS AND REGULATION BY VISUAL INPUT IN ADULTHOOD

Subunit proteins that make up functional GABA(A) receptors were locali zed by immunocytochemistry in the primary visual cortex (area 17) of a dult monkeys and humans. Immunoreactivity for the alpha 1, beta 2/3, a nd gamma 2 subunits is greatest in layers (II-III, IVA and IVC) of mon key area 17 that contain the highest density of GABA neurons and termi nals. Immunostaining for each subunit is unevenly distributed in layer s II and III, where patches of immunoreactivity correspond to regions of intense cytochrome oxidase (CO) staining, and in layer IVA, where i ntense immunoreactivity forms a honeycomb pattern identical to the CO staining pattern. Immunoreactivity for the subunits is localized princ ipally within the neuropil, which, by simultaneous comparison with the distribution of microtubule-associated protein immunostaining, was fo und to include bundles of thin dendrites and zones of numerous dendrit ic segments. In addition, gamma 2 immunostaining surrounds the somata of a subpopulation of GABAergic neurons, immunoreactive for the calciu m-binding protein parvalbumin. All three subunits are present in the s omata and processes of neurons that occupy the white matter subjacent to monkey area 17. In human visual cortex, the alpha 1, beta 2/3, and gamma 2 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 mu m wide) alternate with wider stripes of pale immunostaining (30 -60 mu m wide). In the upper and lower halves of IVC beta, these strip es form lattices similar to those in layers IVC and IVA of monkeys.Fol lowing monocular deprivation by intravitreal injections of TTX in adul t 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 alph a 1, beta 2/3, and gamma 2 occurs in normal-eye stripes while abnormal ly light immunostaining is present in deprived-eye stripes. For all th ree subunits, immunoreactivity in deprived-eye stripes is reduced with in 5 d of monocular deprivation and remains abnormally low for depriva tions that extend to at least 30 d. These findings indicate that each of several GABA(A) receptor subunits adopt similar laminar and compart mental distributions in monkey and human area 17 and are likely to be expressed by the same neurons. The deprivation-dependent reduction in immunoreactivity for alpha 1, beta 2/3, and gamma 2 subunits suggests that all are regulated by visually driven activity. Together with the previously observed reduction in GABA immunoreactivity, the downregula tion of GABA(A) accepters would be expected to leave the deprived-eye column with reduced levels of GABA-mediated inhibition, most likely co ntributing to the functional adaptation seen in visually deprived adul t monkeys.