Distribution and plasticity of immunocytochemically localized GABA_A receptors in adult monkey visual cortex

Immunocytochemical methods were used to reveal new details of the distribution and plasticity of GABA_A receptors in the visual cortex of adult monkeys; the findings were compared with those of autoradiographic experiments involving the binding of ³H-muscimol and ³H-flunitrazepam. In both areas 17 and 18, a monoclonal antibody to the purified GABA_A complex (deBlas et al., 1988) produced staining of punctate profiles in the neuropil and around cell bodies and large processes in layers I-VI. The receptor immunostaining was relatively intense in layers II-III, IVA, IVCβ, and VI; these alternated with lightly stained layers I, IVB, IVCα, and V. In area 18, the laminar pattern was similar except that layer IV was split into a superficial, lightly stained half and a deep, intensely stained half. In sections cut parallel to the pial surface, receptor distribution in most layers was found to be uniform. There were 3 exceptions in area 17: (1) patches of intense receptor staining were present in layers II and III; (2) a widely spaced, irregular lattice of intense staining was found in layer IVA; and (3) a much finer, regular lattice was present in layer IVC. The patches in layers II-III and the lattice in layer IVA coincided precisely with regions of intense cytochrome oxidase (CO) staining. The binding of ³H-muscimol and ³H-flunitrazepam revealed a laminar pattern that was similar in most respects, including greater ligand binding in layer IVA of area 17, but showed no evidence of the sublaminar organization in layers IVA and IVCβ. Inhomogeneities in receptor immunostaining but not ligand binding were also seen in layer III of area 18. Following a 5 or 10 d period in which intravitreal injections of TTX had silenced ganglion cell activity in one retina, GABA_A receptor immunostaining in layer IVCβ was distributed in intensely stained stripes, 450-550 μm wide, that alternated with narrower, lightly stained stripes. Stripes were also seen with receptor immunostaining and with the binding of the 2 radioligands in layer IVCβ of monocularly enucleated monkeys. Comparison with CO staining revealed that the stripes of reduced immunostaining or ligand binding corresponded to columns dominated by the TTX-injected or enucleated eye. Quantitatively, the binding in the deprived eye columns was reduced by 25%. These findings indicate that the distribution of GABA_A receptors in monkey area 17 closely matches the previously reported distribution of cells and axon terminals immunoreactive for GABA and suggest that GABA_A receptors in adult monkeys undergo a rapid, activity-dependent change in density or structure with monocular deprivation.