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

Author(s):  
Péter Szocsics ◽  
Péter Papp ◽  
László Havas ◽  
Masahiko Watanabe ◽  
Zsófia Maglóczky

AbstractBetz 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.

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2019
Author(s):  
Salvatore Desantis ◽  
Serena Minervini ◽  
Lorenzo Zallocco ◽  
Bruno Cozzi ◽  
Andrea Pirone

The pig has been increasingly used as a suitable animal model in translational neuroscience. However, several features of the fast-growing, immediately motor-competent cerebral cortex of this species have been adequately described. This study analyzes the cytoarchitecture of the primary motor cortex (M1) of newborn, young and adult pigs (Sus scrofa domesticus). Moreover, we investigated the distribution of the neural cells expressing the calcium-binding proteins (CaBPs) (calretinin, CR; parvalbumin, PV) throughout M1. The primary motor cortex of newborn piglets was characterized by a dense neuronal arrangement that made the discrimination of the cell layers difficult, except for layer one. The absence of a clearly recognizable layer four, typical of the agranular cortex, was noted in young and adult pigs. The morphometric and immunohistochemical analyses revealed age-associated changes characterized by (1) thickness increase and neuronal density (number of cells/mm2 of M1) reduction during the first year of life; (2) morphological changes of CR-immunoreactive neurons in the first months of life; (3) higher density of CR- and PV-immunopositive neurons in newborns when compared to young and adult pigs. Since most of the present findings match with those of the human M1, this study strengthens the growing evidence that the brain of the pig can be used as a potentially valuable translational animal model during growth and development.


2022 ◽  
Vol 15 ◽  
Author(s):  
Ru Ma ◽  
Xinzhao Xia ◽  
Wei Zhang ◽  
Zhuo Lu ◽  
Qianying Wu ◽  
...  

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Yang ◽  
Ines Eisner ◽  
Siqi Chen ◽  
Shaosong Wang ◽  
Fan Zhang ◽  
...  

While neuroplasticity changes measured by transcranial magnetic stimulation have been proved to be highly correlated to motor recovery and have been tested in various forms of interventions, it has not been applied to investigate the neurophysiologic mechanism of acupuncture therapy. The aim of this study is to investigate neuroplasticity changes induced by a single session of acupuncture therapy in healthy adults, regarding the excitability change on bilateral primary motor cortex and interhemispheric inhibition. Ten subjects took a 30-minute acupuncture therapy and the same length relaxing phase in separate days. Transcranial magnetic stimulation measures, including resting motor threshold, amplitudes of motor-evoked potential, and interhemispheric inhibition, were assessed before and 10 minutes after intervention. Acupuncture treatment showed significant changes on potential amplitude from both ipsilateral and contralateral hemispheres to acupuncture compared to baseline. Also, interhemispheric inhibition from the contralateral motor cortex to the opposite showed a significant decline. The results indicated that corticomotoneuronal excitability and interhemispheric competition could be modulated by acupuncture therapy on healthy subjects. The following question about whether these changes will be observed in the same way on stroke patients and whether they correlate with the therapeutic effect on movement need to be answered by following studies. This trial is registered with ISRCTN13074245.


2010 ◽  
Vol 22 (3) ◽  
pp. 427-436 ◽  
Author(s):  
Leonora Wilkinson ◽  
James T. Teo ◽  
Ignacio Obeso ◽  
John C. Rothwell ◽  
Marjan Jahanshahi

Theta burst transcranial magnetic stimulation (TBS) is considered to produce plastic changes in human motor cortex. Here, we examined the inhibitory and excitatory effects of TBS on implicit sequence learning using a probabilistic serial reaction time paradigm. We investigated the involvement of several cortical regions associated with implicit sequence learning by examining probabilistic sequence learning in five age- and IQ-matched groups of healthy participants following continuous inhibitory TBS over primary motor cortex (M1); or the supplementary motor area (SMA) or dorsolateral prefrontal cortex (DLPFC) or following intermittent excitatory TBS of M1; or after sham TBS. Relative to sham TBS, probabilistic sequence learning was abolished by inhibitory TBS over M1, demonstrating that this region is critical for implicit motor sequence learning. Sequence learning was not significantly affected by inhibitory TBS over the SMA, DLPFC or excitatory TBS over M1. These results demonstrate that the M1 mediates implicit sequence learning.


2018 ◽  
Vol 29 (7) ◽  
pp. 2924-2931 ◽  
Author(s):  
M Wischnewski ◽  
M Engelhardt ◽  
M A Salehinejad ◽  
D J L G Schutter ◽  
M -F Kuo ◽  
...  

Abstract Transcranial alternating current stimulation (tACS) has been shown to modulate neural oscillations and excitability levels in the primary motor cortex (M1). These effects can last for more than an hour and an involvement of N-methyl-d-aspartate receptor (NMDAR) mediated synaptic plasticity has been suggested. However, to date the cortical mechanisms underlying tACS after-effects have not been explored. Here, we applied 20 Hz beta tACS to M1 while participants received either the NMDAR antagonist dextromethorphan or a placebo and the effects on cortical beta oscillations and excitability were explored. When a placebo medication was administered, beta tACS was found to increase cortical excitability and beta oscillations for at least 60 min, whereas when dextromethorphan was administered, these effects were completely abolished. These results provide the first direct evidence that tACS can induce NMDAR-mediated plasticity in the motor cortex, which contributes to our understanding of tACS-induced influences on human motor cortex physiology.


2021 ◽  
Author(s):  
Ru Ma ◽  
Xinzhao Xia ◽  
Wei Zhang ◽  
Zhuo Lu ◽  
Qianying Wu ◽  
...  

Temporal interference (TI) stimulation is a new technique of noninvasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidate. In this study, this issue is investigated in the human primary motor cortex. Participants attended three sessions of TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation. The results indicate that TI stimulation with different envelope frequencies influenced different motor functions. In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential. These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time.


2020 ◽  
Author(s):  
Chaoyue Wang ◽  
Sean Foxley ◽  
Olaf Ansorge ◽  
Sarah Bangerter-Christensen ◽  
Mark Chiew ◽  
...  

AbstractSusceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology.Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices.Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex.Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.


2009 ◽  
Vol 102 (6) ◽  
pp. 3180-3190 ◽  
Author(s):  
Monika Pötter-Nerger ◽  
Sarah Fischer ◽  
Claudia Mastroeni ◽  
Sergiu Groppa ◽  
Günther Deuschl ◽  
...  

Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1HAND) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression (LTD)–like or long-term potentiation (LTP)–like plasticity in left M1HAND through different afferents. We hypothesized that the left M1HAND would integrate LTP- and LTD-like plasticity in a homeostatic fashion. In ten healthy volunteers, low-intensity repetitive transcranial magnetic stimulation (rTMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1HAND via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve and left M1HAND to induce spike-time–dependent plasticity in sensory-to-motor inputs to left M1HAND. We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PASN20+2ms) or an LTD-like decrease (PASN20−5ms) in corticospinal excitability. The amplitude of motor-evoked potentials was recorded from intrinsic hand muscles to assess stimulation-induced changes in corticospinal excitability. Premotor-to-motor preconditioning triggered a homeostatic response to subsequent sensory-to-motor PAS. After facilitatory 5 Hz rTMS, “facilitatory” PASN20+2ms suppressed corticospinal excitability. Likewise, “inhibitory” PASN20−5ms facilitated corticospinal excitability after “inhibitory” 1 Hz rTMS. There was a negative linear relationship between the excitability changes induced by PMD rTMS and those elicited by subsequent PAS. Excitability changes were not paralleled by changes in performance during a finger-tapping task. These results provide evidence for a homeostatic response pattern in the human M1HAND that integrates acute plastic changes evoked through different “input channels.”


2003 ◽  
Vol 270A (2) ◽  
pp. 137-151 ◽  
Author(s):  
Claire-B�n�dicte Rivara ◽  
Chet C. Sherwood ◽  
Constantin Bouras ◽  
Patrick R. Hof

2016 ◽  
Vol 115 (4) ◽  
pp. 2191-2198 ◽  
Author(s):  
Marc R. Kamke ◽  
Abbey S. Nydam ◽  
Martin V. Sale ◽  
Jason B. Mattingley

Paired associative stimulation (PAS) induces changes in the excitability of human sensorimotor cortex that outlast the procedure. PAS typically involves repeatedly pairing stimulation of a peripheral nerve that innervates an intrinsic hand muscle with transcranial magnetic stimulation over the representation of that muscle in the primary motor cortex. Depending on the timing of the stimuli (interstimulus interval of 25 or 10 ms), PAS leads to either an increase (PAS25) or a decrease (PAS10) in excitability. Both protocols, however, have been associated with an increase in excitability of nearby muscle representations not specifically targeted by PAS. Based on these spillover effects, we hypothesized that an additive, excitability-enhancing effect of PAS25 applied to one muscle representation may be produced by simultaneously applying PAS25 or PAS10 to a nearby representation. In different experiments prototypical PAS25 targeting the left thumb representation [abductor pollicis brevis (APB)] was combined with either PAS25 or PAS10 applied to the left little finger representation [abductor digiti minimi (ADM)] or, in a control experiment, with PAS10 also targeting the APB. In an additional control experiment PAS10 targeted both representations. The plasticity effects were quantified by measuring the amplitude of motor evoked potentials (MEPs) recorded before and after PAS. As expected, prototypical PAS25 was associated with an increase in MEP amplitude in the APB muscle. This effect was enhanced when PAS also targeted the ADM representation but only when a different interstimulus timing (PAS10) was used. These results suggest that PAS-induced plasticity is modified by concurrently targeting separate motor cortical representations with excitatory and inhibitory protocols.


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