Perisomatic innervation and neurochemical features of giant pyramidal neurons in both hemispheres of the human primary motor cortex

Abstract

Betz cells—the gigantopyramidal neurons found in high amount in the primary motor cortex—are among of the most characteristic neuronal cells. A part of them contains the calcium-binding protein parvalbumin (PV) in primates. However, less is known about these cells in the human motor cortex despite their important role in different neurological disorders. Therefore, the aim of our study was to investigate the neurochemical features and perisomatic input properties of Betz cells in control human samples with short post-mortem interval. We used different microscopic techniques to investigate the primary motor cortex of both hemispheres. The soma size and density, and expression of PV of the Betz cells were investigated. Furthermore, we used confocal fluorescent and electron microscopy to examine their perisomatic input. The soma size and density showed moderate variability among samples and hemispheres. Post-mortem interval and hemispherical localization did not influence these features. Around 70% of Betz cells expressed PV, but in less intensity than the cortical interneurons. Betz neurons receive dense perisomatic input, which are mostly VIAAT- (vesicular inhibitory amino acid transporter) and PV immunopositive. In the electron microscope, we found PV-immunolabelled terminals with asymmetric-like synaptic structure, too. Terminals with morphologically similar synaptic specialisation were also found among vGluT2- (vesicular glutamate transporter type 2) immunostained terminals contacting Betz cells. Our data suggest that Betz cells’ morphological properties showed less variability among subjects and hemispheres than the density of them. Their neurochemical and perisomatic input characteristics support their role in execution of fast and precise movements.

Differential NPY-Y1 Receptor Density in the Motor Cortex of ALS Patients and Familial Model of ALS

“…This is in line with previous literature that shows that NPY interneurons are predominantly distributed between superficial cortical layers 1-3 and release NPY into cortical layer 1 via horizontal processes [56,66]. Functionally, this may reflect the degree of synaptic innervation required for subcellular compartments to appropriately influence the output of upper motor neuron signaling [47]. Furthermore, we observed an age associated increase to the density of NPY-Y1 receptors in the rodent motor cortex between 8 and 20 weeks of age which could suggest that this receptor has a key role in adaptive plasticity mechanisms of the motor cortex.…”

“…The activity and function of motor neurons rely upon appropriate innervation of subcellular domains, thereby differentially regulating input, integration and output. This includes the dense perisomatic innervation received by upper motor neurons from within layer 5 of the motor cortex, which strongly influences cell output [47], and the axo-dendritic innervation received from layer 2/3 cells onto upper motor neuron apical dendrites, which influences temporal summation [48][49][50]. In the post-mortem ALS patient motor cortex, upper motor neurons undergo marked cellular and dendritic degeneration, which includes reduced numbers of excitatory post-synaptic connections on apical processes [51,52].…”

Betz cells of the primary motor cortex

“…Like other pyramidal cells, Betz cells are surrounded by an extracellular matrix of chondroitin sulfate proteoglycan-immunoreactive perineuronal nets (Hausen et al, 1996). Finally, the soma of human Betz cells receives a dense array of synapses from parvalbumin-expressing interneurons (Szocsics et al, 2021), consistent with the importance of inhibitory control required for the execution of finely tuned corticospinal volitional movement.…”

Giant pyramidal neurons of the primary motor cortex express vasoactive intestinal polypeptide (VIP), a known marker of cortical interneurons

“…Betz cells can be evidenced using markers of pyramidal neurons, such as antibodies against non-phosphorylated neurofilament (e.g. SMI-32; Tsang et al, 2000; Szocsics et al, 2021), as well as general markers of neuronal nuclei (e.g. NeuN; Szocsics et al, 2021).…”