Multiple types of nitrogen monoxide synthase-/NADPH diaphorase-containing neurons in the human cerebral neocortex

Nitrogen monoxide (NO) synthase (NOS)-containing neurons (NOSN) were identified by means of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry in nine areas of the human cerebral neocortex from patients 9-74 years of age. Labeled neurons were analyzed according to their disposition in the various layers of the cortical gray and immediately subjacent white matter, and classified according to their cytological features. The vast majority of NOSN (about 80%) are situated in the subcortical white matter and not in the cortical gray proper. Nevertheless, these NOSN extend their processes into the cortical gray and thus appear to participate in intracortical circuits, along with the minority of NOSN situated in all cortical layers. Although many NOSN are small aspiny local circuit neurons, as reported previously, additional distinct cytological types of NADPH diaphorase-positive neurons were also identified, including: (a) local circuit neurons in layer I; (b) granule cells in layer II, and (c) non-pyramidal neurons with densely spinous dendrites in the white matter immediately under the cortical gray. Processes fulfilling light microscopic criteria for axons were seen in many of the above cell types originating from proximal dendrites and, less frequently, from a presumed axon hillock. Taken together, these observations indicate that NOSN belong to several distinct morphological and presumably functional classes, some of which have a unique or restricted laminar location, raising the possibility that some of these various classes of neurons may be selectively affected or spared in neurodegenerative disorders.