The discovery of the pyramidal neurons: Vladimir Betz and a new era of neuroscience

Abstract

As a consequence of nascent technology, the 19th century witnessed a profound change in orientation to the nervous system. For example, improved microscopy in the first half of the 19th century allowed high magnification without blurring. The subsequent observation of nucleated cells led to the identification of individual brain cells. Philosophical changes in approach to the natural sciences took their lead from those applied to physical observations. The Ukrainian anatomist and histologist, Vladimir Alekseyevich Betz (1834-94) played a pivotal role in reshaping scientific and philosophical approaches to the brain, connecting cerebral localization, function and brain microstructure. Betz revolutionized methods of cell fixation and staining. Sometimes his efforts yielded enormously complicated technological improvements. Betz's greatest contribution, however, was connecting his discovery of the function of giant pyramidal neurons of the primary motor cortex ('cells of Betz') with the cortical organization. Considering cortical cytoarchitectonics in relation with physiological function, Betz recognized this organization in two areas: motor and sensory. He defined a functional area on histological grounds and thereby opened the way to study precise cortical areas. Betz participated in the scientific transformation of cytoarchitectonics based on macro- and microscopic studies of the cortical surface, enabling him to view the paths of nerve cells in the brain. Betz's influence allowed systemization of scattered scientific findings. The discovery of pyramidal cells was a turning point in the prevailing philosophical and scientific approach to the brain, linking cytoarchitecture, neurophysiology and cerebral localization.

Pathological TDP-43 changes in Betz cells differ from those in bulbar and spinal α-motoneurons in sporadic amyotrophic lateral sclerosis

“…More recently, the same pattern of pathological changes has been reproduced in neuroimaging-based studies [33, 36, 53, 67]. In stage 1, pTDP-43 pathology is found in the Betz cells of Brodmann field 4 [38] in the neocortex and in bulbar and spinal α -motoneurons with the exception of the motoneurons that control the extrinsic eye muscles [1, 13]. The topographical distribution of the lesions in stage 2 is marked by the development of pTDP-43 inclusions in parvocellular projection neurons of the red nucleus and, in stage 3, in medium-sized projection neurons of the caudate nucleus and putamen [13].…”

“…After fixation, the hemispheres were cut perpendicular to Forel’s axis using a macrotome into 1 cm thick slices and embedded in polyethylene glycol (PEG 1000, Merck) according to a previously published protocol [11]. Tissue sectioning was performed with a tetrander (Jung, Heidelberg, Germany) at a thickness of 100 µm to insure that the Betz cells could be studied in their entirety without sectioning artifacts, i.e., at a thickness exceeding the average diameter of a giant pyramidal Betz cell [5, 38]. …”

Does Sporadic Amyotrophic Lateral Sclerosis Spread via Axonal Connectivities?

“…Naturally, the duration and transition of each stage cannot be determined within the context of post-mortem cross-sectional studies; nevertheless, in vivo diffusion-tensor imaging (DTI) and diffusion-weighted imaging (DWI)-based results gained from ALS patients fit in well with the proposed hypothetical sequence of neuropathological staging [20][21][22][23][24]. stage 1: Abnormal changes develop not only in Betz pyramidal cells in the deep layer Vb of the primary motor cortex (Brodmann field 4) [25] but also in lower brainstem and spinal cord α-motor neurons (▶Fig. 1, 2) [3].…”

“…They are readily distinguishable from other cell types of the central nervous system and, thus, well-suited for delineating the development of the TDP-43 pathology in both neuronal types (▶ Fig. 2) [25].…”

“…They are readily distinguishable from other cell types of the central nervous system and, thus, well-suited for delineating the development of the TDP-43 pathology in both neuronal types (▶ Fig. 2) [25].Beginning in stage 1, it is possible to see alongside of the many normal Betz cells and α-motor neurons displaying strong TDP-43-positive intranuclear staining an increasing number of the same cell types with reduced intranuclear TDP-43 immunostaining. In time and with disease progression, the nuclei of such cells completely lack TDP-43 immunoreactivity.…”