Long‐distance corticocortical GABAergic neurons in the adult monkey white and gray matter

Abstract A subgroup of GABAergic neurons has been reported to project over long distances in several species. Here we demonstrate that long‐distance cortically projecting nonpyramidal neurons occur in monkeys in both white and gray matter. Nonpyramidal neurons were first identified morphologically. Visualization of Golgi‐like details was achieved by retrograde infection from injections of an adenovirus vector, producing enhanced green fluorescent protein (EGFP) under control of a neuron‐specific promoter. Injections in areas V1, V4, TEO, and posterior TE resulted in EGFP‐expressing nonpyramidal neurons up to 1.5 cm distant from the injections, mainly in the white matter. Some neurons occurred in the gray matter, mainly in layer 3, but also in layers 5 and 6, and, very occasionally, layer 1. As control, we injected cholera toxin subunit B, a standard retrograde tracer, in V4, and observed a similarly wide distribution of neurons in the white matter. Second, the GABAergic identity of EGFP‐expressing nonpyramidal neurons was established by colabeling for EGFP and GAD67 in selected tissue sections. Most neurons positive for EGFP and GAD67 were positive for somatostatin (SS; 90%). Of those neurons positive for EGFP and SS, almost all were also positive for neuronal nitric oxide synthase or m2 muscarinic receptor, but only 23% were also positive for calretinin. None were positive for parvalbumin. We conclude that long‐distance projecting GABAergic neurons 1) are phylogenetically conserved, although in monkeys most gray matter neurons are in the upper layers, and 2) are heterogeneous in terms of their neurochemistry, location, and potentially function. J. Comp. Neurol. 505:526–538, 2007. © 2007 Wiley‐Liss, Inc.