Nitrinergic neurons in the developing and adult human telencephalon: transient and permanent patterns of expression...

A subpopulation of cerebral cortical neurons constitutively express nitric oxide synthase (NOS) and, upon demand, produce a novel messenger molecule nitric oxide (NO) with a variety of proposed roles in the developing, adult, and diseased brain. With respect to the intensity of their histochemical (NADPH-diaphorase histochemistry) and immunocytochemical (nNOS and eNOS immunocytochemistry) staining, these nitrinergic neurons are generally divided in type I and type II cells. Type I cells are usually large, intensely stained interneurons, scattered throughout all cortical layers; they frequently co-express GABA, neuropeptide Y, and somatostatin, but rarely contain calcium-binding proteins. Type II cells are small and lightly to moderately stained, about 20-fold more numerous than type I cells, located exclusively in supragranular layers, and found almost exclusively in the primate and human brain. In the developing cerebral cortex, nitrinergic neurons are among the earliest differentiating neurons, mostly because the dominant population of prenatal nitrinergic neurons are specific fetal subplate and Cajal-Retzius cells, which are the earliest generated neurons of the cortical anlage. However, at least in the human brain, a subpopulation of principal (pyramidal) cortical neurons transiently express NOS proteins in a regionally specific manner. In fact, transient overexpression of NOS-activity is a well-documented phenomenon in the developing mammalian cerebral cortex, suggesting that nitric oxide plays a significant role in the establishment and refinement of the cortical synaptic circuitry. Nitrinergic neurons are also present in human fetal basal forebrain and basal ganglia from 15 weeks of gestation onwards, thus being among the first chemically differentiated neurons within these brain regions. Finally, a subpopulation of human dorsal pallidal neurons transiently express NADPH-diaphorase activity during midgestation.