Perineuronal nets in the cortical white matter – visualized with WFA (Wisteria floribunda agglutinin) in adult macaque monkeys

Purpose: To characterize the distribution of white matter neurons (WMNs) positive for perineuronal nets (PNNs) in the adult monkey. WMNs are a mixed population of excitatory and inhibitory neurons. They have an important role in axon guidance during cortical development, but their role in the adult brain is less understood. In vitro and in vivo experiments provide evidence that WMNs are incorporated into cortical circuitry. The majority of investigations in the adult, however, have focused on regional variations in overall density, or on characterization of morphological and neurochemical subtypes. The present study was motivated by the observation that some WMNs exhibit PNNs in adult monkey. Since PNNs are associated with plasticity in younger animals, their occurrence with some WMNs might be functionally significant. Methods: PNNs were visualized, at the light microscopic level, by WFA staining in three adult macaque brains. Density of WFA positive WMNs was scored at three anterior-posterior levels (frontal, mid-hemispheric, and occipital), and compared with overall density of WMNs, as visualized by immunocytochemistry for NeuN. Quantitation of WFA+ neurons and neuron morphology were analyzed via light microscopy. Soma size and appearance, and dendritic length were recorded and measured. vi Results: On the basis of soma size and proximal dendritic shape, several types of WFA+ WMNs were provisionally identified, consistent with previous reports in the literature. Subpopulation densities were of highest density in mid-cortical areas and lowest quantities at occipital, matching previous studies. Morphological measurements suggested a heterogeneous neuron population through soma measurements and dendrite orientation. Soma sizes exhibited a range of circularity and size (10 μm – 30 μm). Dendrites were stained beyond the “proximal” area, including intermediate areas beyond the first branch, and up to 500 μm. Conclusions: A small population of WMNs are coated by PNNs in adult monkey. On the basis of morphology, these might be further subdivided, but combined studies with other markers would be needed. Future studies might investigate ageor pathology-related changes in the density and subtypes of WMNs that express PNNs in human or nonhuman primates. We speculate that these WMNs might have functional specializations, perhaps similar to the plasticity effects documented for PNNs in early development.