Skeletal muscles are force generators allowing interaction of the organism with the environment. When muscle contractions are repeated or sustained, after some time fatigue will develop and this will ultimately affect performance. Although everyone has already experienced fatigue, it is not easy to provide a clear definition, as fatigue is a multifactorial process and differs between situations. In our laboratory, we aim to elucidate the mechanisms underlying muscle fatigue in particular, and more generally investigate the muscle response to training or disease by assessing neuromuscular plasticity (i.e. neural and muscular adaptations). We use techniques such as electrical stimulation through the skin and recording of electrical activity of the muscles when they contract to distinguish central (neural) from peripheral (muscular) adaptations. We also use in vitro models (e.g. isolated mouse and human muscle fibers, human muscle biopsy analysis) to determine cellular/molecular mechanisms underlying what can be measured in exercising humans.
Examples of research lines in the laboratory:
- Combination of integrative and mechanistic approaches to study muscle plasticity;
- Wide-pulse, high-frequency neuromuscular electrical stimulation;
- Methodological studies.
Combination of integrative and mechanistic approaches to study neuromuscular plasticity
The main focus in the laboratory is currently to develop a translational research combining both integrative and mechanistic approaches to delve deeper into the mechanisms underlying muscle fatigue and muscle adaptations to training. To this end we combine measures obtained on exercising humans, muscle biopsies, mouse intact/skinned single fibers and mouse isolated muscle, in order to investigate in detail the excitation-contraction coupling, and in particular the role of Ca2+ handling.
As such, we are particularly interested in the effect of exercise on the ryanodine receptor type 1 (RyR1, see right panel of the figure), the sarcoplasmic reticulum Ca2+ release channel. We recently showed that RyR1 is central in the adaptations to high intensity exercise, as only one single session of high intensity interval training can markedly affect RyR1, which would in turn trigger the beneficial muscular adaptations of endurance training. Other investigations are ongoing in that direction.
Other projects using the same approach (i.e. combination of measurement from in vitro and in vivo models) aim to determine the impact of caffeine on neuromuscular adaptations to exercise or to provide new insights into the validity of already established techniques, such as the twitch interpolation technique.
Image: Broad Institute Communications
From Bellinger et al. J Clin Invest 2008
Wide-pulse, high-frequency neuromuscular electrical stimulation
Neuromuscular electrical stimulation is a widely used tool to enhance, restore or preserve muscle function via the application of intermittent transcutaneous electrical stimulations. It is a method that has proven to have beneficial effects both in athletes and in clinical populations. However, there are two main pitfalls associated with this technique: (i) motor unit recruitment differs in comparison to voluntary contractions, which usually results in premature fatigue and (ii) the need for large stimulation intensity induces discomfort. Recently, a new stimulation paradigm combining wider pulse duration (1 ms), higher stimulation frequencies (> 80 Hz) and low stimulation intensity has been proposed to overcome these pitfalls, as part of the evoked force (the “extra force”, see right panel of the figure) would be obtained with motor unit recruited according to size principle, i.e. via synaptic activation at the spinal cord level. Our laboratory is interested in the physiological adaptations to wide-pulse, high-frequency neuromuscular electrical stimulation and especially the involvement of the central nervous system in force production in both healthy and clinical populations.
Left: experimental set-up for neuromuscular electrical stimulation of the calf muscles; right: examples of evoked forces using wide-pulse high-frequency NMES in cerebral palsy (CP) patients and control participants (from Neyroud et al., Clin Neurophysiol in press).
The assessment of neuromuscular function is possible when combining voluntary contractions with (i) transcutaneous nerve electrical / magnetic stimulation or (ii) transcranial magnetic stimulation while recording muscle force and surface electromyography. As a variety of parameters are used in the literature, there is a need to get insights into the indexes that are the most sensitive, reliable and valid to properly characterize neuromuscular function. Studies are thus performed to determine for instance the influence of stimulation intensity, pulse duration, stimulation modality (over-the-muscle or nerve stimulation, see image below) on selected outcomes such as the evaluation of neuromuscular fatigue, motor unit recruitment pattern or simply to validate a new method over a standard.
Examples of interpolated and size-matched resting twitches (upper and lower figure, respectively) obtained with muscle vs nerve transcutaneous stimulation (From Place et al. Muscle Nerve 2010)
Bengt Kayser, MD, PhD, chef du groupe.
MD, University of Amsterdam, Netherlands, 1986
Nicolas Place, PhD, maître d’enseignement et de recherche.
After five years spent in Geneva at the institute of movement sciences and sports medicine, I joined the Institute of Sport Sciences of the University of Lausanne and thus the Department of Physiology in 2013. My research focuses on neuromuscular plasticity with a special interest in muscle weakness. Further insights into skeletal muscle adaptations to exercise are ongoing with a translational approach combining non-invasive measurements in humans and in vitro models.
Nadège Zanou, MD, PhD, post-doc.
I am Medical Doctor with Ph.D. in skeletal muscle physiology and pathophysiology obtained in 2012 at the catholic University of Louvain in Belgium. Previously (2013-2015), I was a postdoctoral researcher of the catholic University of Louvain working on the gating mechanisms of TRP ion channel activation in normal and pathological cells. Now First Assistant at the University of Lausanne, I am interested in the cellular and molecular mechanisms of skeletal muscle adaptations to exercise and on the relationship between physical activity and health.
Chris Donnelly, PhD student
Hi! I’m Chris. My main research interest is in neuromuscular plasticity, in particular the molecular basis of the adaptive response of skeletal muscle to exercise and nutrition. My interest extends to the application of the science to athletic and clinical populations.
Originally from Northern Ireland, I obtained my BSc (Hons) in Sport and Exercise Science from The University of Stirling, Scotland and MSc in Sport Nutrition from Liverpool John Moores University, England. Now I am a PhD student in the Kayser-Place lab investigating skeletal muscle fatigue and neuromuscular adaptations to exercise.
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Translational approach to characterize muscle response to exercise:
- Pr Håkan Westerblad, Karolinska Institutet, Stockholm (Sweden)
- Dr Tomas Venckunas, Sports Science and Innovation Institute, Lithuanian Sports University, Kaunas (Lithuania)
- Dr Julien Ochala, Centre of Human and Aerospace Physiological Sciences, King's College, London (UK)
Neuromuscular electrical stimulation (integrative approach):
- Dr Nicola Maffiuletti, Schulthess Klinik, Zurich
- Dr Javier Rodriguez-Falces, Department of Electrical and Electronical Engineering, Public University of Navarra, Pamplona (Spain)
- Dr Julien Gondin, Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille (France)
- Pr Romuald Lepers, INSERM U1093, Faculty of Sport Sciences, University of Bourgogne Franche-Comté, Dijon (France)
- Pr Guillaume Millet, Faculty of Kinesiology, University of Calgary (Canada)