Differential expression of NADPH diaphorase in functionally distinct prefrontal cortices in the rhesus monkey

The prefrontal cortex of primates is an integrative centre for sensory, cognitive, mnemonic and emotional processes. The cellular features which contribute to the functional specialization of its subsectors are poorly understood. In this study we determined the distribution of nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in structurally and functionally distinct prefrontal cortices in the rhesus monkey. This class of neurons express nitric oxide synthase which is necessary for the production of nitric oxide, a novel neural messenger implicated in learning and memory. The density of diaphorase-positive neurons was approximately four times higher in olfactory areas than in eulaminate areas (areas 9, 10, 12, 46, and 8), and two- to three-times higher in the agranular limbic area PAll than in eulaminate areas. Positive neurons were concentrated in a deep band (layers V and VI), a superficial band (layers II and upper III), and were sparsely distributed in the central, thalamic recipient zone (deep layer III, layer IV and upper V). The highest densities of positive neurons were observed in the white matter where their prevalence followed the opposite trend than in the corresponding overlying cortices. The distribution of diaphorase-positive neurons was correlated with the regional anatomic and functional specialization of prefrontal cortices. Thus, diaphorase-positive neurons were most densely distributed in orbital and then medial prefrontal limbic cortices which have a low cell density and widespread connections. In contrast, positive neurons were comparatively sparse in eulaminate cortices, which have a high cell density and more restricted connections. These findings indicated that the distribution of diaphorase-positive neurons in prefrontal cortices is not random, but is associated with the structural architecture and functional attributes of these cortices. The preponderance of diaphorase-positive neurons in limbic cortices, which have been implicated in learning and memory, is consistent with the idea that nitric oxide may have a role in synaptic plasticity.