The distribution, number, and certain neurochemical identities of infracortical white matter neurons in a lar gibbon (Hylobates lar) brain

Abstract

We examined the number, distribution, and immunoreactivity of the infracortical white matter neuronal population, also termed white matter interstitial cells (WMICs), in the brain of a lesser ape, the lar gibbon. Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most numerous and dense close to cortical layer VI, decreasing significantly in density with depth in the white matter. Stereological analysis of NeuN‐immunopositive cells revealed a global estimate of ~67.5 million WMICs within the infracortical white matter of the gibbon brain, indicating that the WMICs are a numerically significant population, ~2.5% of the total cortical gray matter neurons that would be estimated for a primate brain the mass of that of the lar gibbon. Immunostaining revealed subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS, ~7 million in number, with both small and large soma volumes), calretinin (~8.6 million in number, all of similar soma volume), very few WMICs containing parvalbumin, and no calbindin‐immunopositive neurons. These nNOS, calretinin, and parvalbumin immunopositive WMICs, presumably all inhibitory neurons, represent ~23.1% of the total WMIC population. As the white matter is affected in many cognitive conditions, such as schizophrenia, autism and also in neurodegenerative diseases, understanding these neurons across species is important for the translation of findings of neural dysfunction in animal models to humans. Furthermore, studies of WMICs in species such as apes provide a crucial phylogenetic context for understanding the evolution of these cell types in the human brain.

Long‐range projections from sparse populations of GABAergic neurons in murine subplate

“…These NADPH diaphorase positive cells develop by 15 GW in human frontal cortex, in the emergent subplate (Yan, Garey, & Jen, ). NADPH diaphorase positive cells in cat white matter and layer 6b can have long‐range projections (Higo, Udaka, & Tamamaki, ), and long‐range projecting, nNOS+ cells were also found in the white matter of monkeys (Swiegers et al, ; Tomioka & Rockland, ).…”

Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders

“…WM neurons are normally distributed in high densities in the superficial WM, with their densities decreasing with increasing depth of the WM (low densities in the deep WM) towards the deep WM . These cells are found in abundance in the WM at the apices of the cerebral gyri and are relatively sparse in the WM at the bases of the sulci . There are also regional differences in the abundance of the superficial WM neurons; while they are found in abundance in the superficial WM of the frontal and cingulate cortices, the cells are relatively sparse in the visual and temporal cortices .…”

“…Although most neocortical neurons are distributed in the gray matter, the neocortical WM also contains some neurons in primates, including humans. Since the major components of the WM are the axonal fibers, surrounding myelin sheath, and supporting glial cells, neurons scattered in the WM were once called ‘interstitial neurons’ by Santiago Ramón y Cajal . While these cells have been referred to by various names, such as ‘subcortical cells,’ ‘extracortical (non‐plate) neurons,’ ‘outlying cells,’ ‘subcortical plate (subplate) cells,’ ‘white matter interstitial cells,’ and ‘subcortical white matter interstitial cells,’ they are most commonly referred as ‘white matter (WM) neurons,’ and the author uses this term in the present paper.…”

“…There are also regional differences in the abundance of the superficial WM neurons; while they are found in abundance in the superficial WM of the frontal and cingulate cortices, the cells are relatively sparse in the visual and temporal cortices . Recent analysis of a lar gibbon brain revealed that the WM contained around 67.5 million neurons, corresponding to about 2.5% of the number of neurons in the cortical gray matter . Approximately 25% of the total population of WM neurons in the lar gibbon brain were thought to be inhibitory (GABAergic) neurons …”

“…Recent analysis of a lar gibbon brain revealed that the WM contained around 67.5 million neurons, corresponding to about 2.5% of the number of neurons in the cortical gray matter . Approximately 25% of the total population of WM neurons in the lar gibbon brain were thought to be inhibitory (GABAergic) neurons …”