Neuronal nitric oxide synthase (nNOS) is constitutively expressed by subpop
ulations of neurons in the CNS and is involved in neurotransmission, learni
ng and memory, and neuronal injury. While the distribution of nNOS neurons
has been characterized in the rodent CNS, the expression in human brain has
not been well documented. We determined the expression of nNOS in second t
rimester human fetal and adult brain. In second trimester fetal brain, the
nNOS neurons are concentrated in the developing cerebral cortex at the subp
late zone and in layer VI, the striatum, and in certain brainstem nuclei. T
he nNOS neurons are sparsely distributed in the hippocampus, and virtually
absent in the cerebellar cortex. The nNOS neurons in the subplate zone exte
nd their processes radially, suggesting a developmental role, perhaps in gu
idance. The number and distribution of NADPH diaphorase-positive neurons co
rresponds to that of the nNOS neurons. While the distribution of nNOS neuro
ns in the adult brain is similar to that found in fetal brain, the overall
density is lower in the adult. The highest density of nNOS neurons is found
in the striatum followed by the neocortex. A region-specific role for nNOS
neurons in human brain and a potential developmental role for nNOS in the
cerebral cortex are suggested by these data.