Cytoarchitecture of the mouse neocortex revealed by the low-molecular-weight neurofilament protein subunit

Abstract

The expression patterns of the medium- and high-molecular-weight subunits of the neurofilament protein triplet have been extensively studied in several neuroanatomical studies. In the present study, we report the use of the low-molecular-weight neurofilament protein subunit (NF-L) as a reliable marker within the neurofilament protein family to reveal the regional architecture of mammalian neocortex. We document clearly its usefulness in anatomical parcellation studies and report unique expression patterns of NF-L throughout the mouse neocortex. NF-L was most abundant in the somatosensory cortex, the lateral secondary visual area, the granular insular cortex, and the motor cortex. Low NF-L staining intensity was observed in the agranular insular cortex, the prelimbic and infralimbic cortex, the anterior cingulate cortex, the visual rostromedial areas, the temporal association cortex, the ectorhinal cortex, and the lateral entorhinal cortex. NF-L immunoreactivity was present in the perikarya, dendrites, and proximal segment of axons primarily of pyramidal neurons, and was mainly located in layers II and III, and to a lesser extent in layers V and VI. Interestingly, Black-Gold myelin staining confirmed a close correlation between NF-L immunoreactivity and myelination patterns. The characteristic and distinctive distribution and laminar expression profiles of NF-L make it an excellent tool to assess accurately topographical boundaries among neocortical areas as illustrated herein in the adult mouse brain.

Neurites containing the neurofilament-triplet proteins are selectively vulnerable to cytoskeletal pathology in Alzheimer’s disease and transgenic mouse models

“…A cocktail comprising SMI32 and SMI312 antibodies was used to label the NF + subpopulation of neurites, which we assume are chiefly derived from pyramidal cells of cortical layers 2–6 (Van der Gucht et al, 2007; Paulussen et al, 2011). Although neurites from a subset of basket cells, or projecting fibers from subcortical and subthalamic regions, would also be NF + (Hof and Morrison, 1990; Hof et al, 1990), their fewer numbers and less extensive neurite fields indicates that pyramidal neurites make up the majority of NF + processes examined in cortical layers 2–4 (Hof et al, 1995).…”

“…Neurofilament triplet proteins belong to the type IV intermediate filament protein family, and, in the neocortex of many mammalian species, are predominantly expressed by a pyramidal subpopulation in layers 2–6 making corticocortical connections (Vickers and Costa, 1992; Hof et al, 1995; Van der Gucht et al, 2007; Paulussen et al, 2011). The NF “triplet” refers to three genetically and structurally interrelated subunits [68 kDa (NF-L), 160 kDa (NF-M), and 200 kDa (NF-H)] that are typically co-expressed, and which co-polymerize to form intermediate filaments (Szaro and Strong, 2010).…”

Comparison of (stereotactic) parcellations in mouse prefrontal cortex

“…We only selected Nissl-stained photographs which contained PFC areas, for the assessment of boundaries in the PFC. The Nissl staining is preferred to delineate the PFC boundaries (Van de Werd et al 2010; Paulussen et al 2011), because Nissl staining has proved to be superior to any other staining in visualizing boundaries in general (Van de Werd and Uylings 2008; Van de Werd et al 2010; Uylings et al 2010). The Nissl staining is also the staining generally applied in morphometric studies, tracing studies and physiological studies for defining the location of an electrode.…”

Isocortex

“…7), the anterior parietal region, which is approximately 1.8 mm thick (Beaulieu, 1993;Skoglund et al, 1996), is characterized by a highly developed inner granular layer IV, which is reflected in the highest GLI value determined in the whole cortex of the rat brain (Zilles, 1990). Anterior parietal areas, in particular Par1, also show the highest degree of myelination of all isocortical areas (Zilles et al, 1980;Zilles, 1985), as well as highest densities of low-molecular-weight neurofilament protein subunits, the location of which correlates closely with myelinated fibers (Paulussen et al, 2011). Layer II is relatively thin and not particularly Roman numerals indicate cortical layers.…”