Neurons in the white matter of the adult human neocortex

Abstract

The white matter (WM) of the adult human neocortex contains the so-called "interstitial neurons" . They are most numerous in the superfi cial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classifi ed as interneurons based on their neurochemical profi le as well as on morphological criteria. WM-interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specifi c prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood fl ow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system.

Early history of subplate and interstitial neurons: from Theodor Meynert (1867) to the discovery of the subplate zone (1974)

“…In contrast, and in full agreement with our data and interpretation (see Judaš et al, 2010), several research groups recently pointed out that interstitial neurons should be regarded as normal and important components of the human and monkey adult white matter and not just as 'a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain ' (Suá rez-Solá et al 2009). Suá rez-Solá et al (2009) justly conclude (p. 2): 'primate interstitial neurons are not just incidental remnants of early-born neurons, but rather seem to belong to a distinct neuronal system that is intimately connected to the white matter and may carry out activities pertinent to this location' -such as coordinating inter-areal connectivity and regulation of blood flow.…”

“…In fact, it has been repeatedly pointed out that the developmental history of the subplate is very different in humans and other primates than in carnivores and rodents (Kostović & Rakic, 1980, 1990Meyer et al 2000;Smart et al 2002;Lukaszewicz et al 2005;Molná r et al 2006;Meyer, 2007;Bayatti et al 2008;Bystron et al 2008;Suá rez-Solá et al 2009). For example, in contrast to the situation in rodents, neurons are continuously added to the subplate in primates during the later stages of corticogenesis (Kostović & Rakic, 1990;Smart et al 2002;Meyer, 2007;Bystron et al 2008).…”

“…It is also usually stated that the term 'interstitial neurons' was coined by Ramó n y Cajal in 1911, either because in his monograph he described 'interstitial nerve cells' in various fibre bundles (Das & Kreutzberg, 1968) or because the name interstitial neurons 'used originally by Ramó n y Cajal (1911) for the cells situated within cerebellar white matter, is appropriate for the cells in the other regions as well' (Kostović & Rakic, 1980, p. 220). Finally, it is generally accepted that interstitial neurons of the cerebral white matter represent a postnatally surviving subset (or 'remnant' or even 'vestige') of transient fetal subplate neurons (Kostović & Rakic, 1980, 1990Luskin & Shatz, 1985;Valverde & Facal-Valverde, 1988;Allendoerfer & Shatz, 1994;, 2007Molná r et al 2006;Clancy et al 2009;Friedlander & Torres-Reveron, 2009;Luhmann et al 2009;Suá rez-Solá et al 2009;Kanold & Luhmann, 2010;.…”

5-HT3AReceptor-Bearing White Matter Interstitial GABAergic Interneurons Are Functionally Integrated into Cortical and Subcortical Networks

“…Thus, the presence of calretinin (Suárez-Solá et al, 2009), calbindin (Yan et al, 1996), VIP (Bayraktar et al, 1997(Bayraktar et al, , 2000, NPY (Adrian et al, 1983;Chan-Palay et al, 1985), cholecystokinin (Innis et al, 1979), substance P (Shults et al, 1984), somatostatin (Somogyi et al, 1984), and nNOS (Sandell, 1986;Tao et al, 1999; Suárez-Solá et al, 2009) was reported for WMICs. Of note, in the transgenic mice employed here, EGFP expression in the corpus callosum was confined by and large to VIP-, calretinin-, and calbindin-positive interneurons.…”

“…Basic morphological features of WMICs were indicative of a neuronal phenotype (Neuburger, 1922;Lund et al, 1975;Kostovic and Rakic, 1980;Chun and Shatz, 1989;Muller, 1994;Shering and Lowenstein, 1994;Eastwood and Harrison, 2005;Friedlander and Torres-Reveron, 2009;Loup et al, 2009), a notion that was also supported by electron microscopy data (Valverde and Facal-Valverde, 1988). While there is ample information about the immunohistochemical signature of WMICs, such as the expression of GABA and specific GABAergic interneuron markers (Innis et al, 1979;Adrian et al, 1983;Schmechel et al, 1984;Shults et al, 1984;Somogyi et al, 1984;Chan-Palay et al, 1985;Sandell, 1986;Yan et al, 1996;Bayraktar et al, 1997;Tao et al, 1999;Suárez-Solá et al, 2009), only a few studies focused on electrophysiological properties of WMICs (Clancy et al, 2001;Torres-Reveron and Friedlander, 2007;Friedlander and Torres-Reveron, 2009). The main hindrance for the identification of WMICs in acute slices is their scarcity.…”