Electromyography: Accessing populations of motor units
A new device improves the way scientists can record the activity of motor units in a wide range of animals and settings.
- Department of Neurosciences, School of Medicine, Case Western Reserve University, United States
Active, purposeful movement is a defining feature of animal life and requires precise coordination between the nervous system and muscles. Specialized nerve cells, known as motoneurons, constitute the final output of the central nervous system, and are responsible for activating muscle. Each motoneuron can innervate multiple muscle fibers, and a single electrical impulse in the motoneuron induces a corresponding impulse in these fibers, causing them to contract. Together, a single motoneuron and the muscle fibers it innervates are referred to as a motor unit (Sherrington, 1925).
Recording the electrical activity of individual motor units during voluntary contractions became possible in the 1920s with the development of needle electrodes that could be inserted into muscles. This approach has revealed many fundamental properties of the neuromuscular system by allowing indirect yet accurate and relatively non-invasive measurement of impulse times in spinal motoneurons (Adrian and Bronk, 1929; Farina and Gandevia, 2023). But it also has many limitations, such as needle electrodes getting displaced during movement and only being able to record a small number of motor units at a time. In addition, it is often challenging to assign a given impulse to a specific unit using this method because an individual electrode may detect impulses with similar electrical profiles from multiple motor units.
However, scientists can bypass some of these limitations. For example, it is possible to reliably isolate the activity of multiple individual units during movement by using a large number of electrodes organized into an array, as each motor unit will produce a unique pattern of waveforms across the electrodes. In recent decades, new techniques have been developed to record from larger numbers of motor units, including high-density electrode arrays that can be implanted into muscle, and arrays that record relatively smaller signals at many sites across the surface of the skin (Muceli et al., 2022; Negro et al., 2016).
While each of these methods has distinct strengths and limitations, there remains a need for a widely available device that is capable of the following: providing stable recordings during natural movements, when muscles rapidly lengthen, shorten, and twist; being used in a broad range of experimental preparations, muscles, and animal groups; recording many motor units simultaneously; and working for weeks or even months after implantation. Now, in eLife, Samuel Sober and colleagues at various institutions in the United States, Canada, Portugal and Germany – including Bryce Chung (Emory University) and Muneeb Zia (Georgia Institute of Technology) as joint first authors – report how they have successfully developed versatile devices called Myomatrix arrays that meet these criteria (Chung et al., 2023).
The instruments consist of four long, flexible threads that each terminate in eight electrodes (Zia et al., 2020; Lu et al., 2022). These threads can either be inserted directly into a muscle or attached to the overlying connective tissue, enabling the electrodes to move with the muscle and maintain stable recordings. Chung et al. first tested the device in freely behaving mice, showing that it provided better recordings of the activity of individual motor units than traditional wire electrodes. The team was then able to demonstrate that Myomatrix arrays could record well-isolated motor units across a wide range of muscle morphologies, species and behaviors: this included the vocal and respiratory muscles of songbirds as they breathed, the hip muscles of bullfrogs during reflex contractions, and the abdominal muscles of hawkmoth larvae undergoing a protocol commonly used in locomotion studies.
Next, Chung et al. showed that their approach could simultaneously provide stable recordings from multiple motor units, including for large muscles and during active movement (for example, for the forelimb muscles of rhesus macaques performing a reaching task). Finally, they successfully confirmed that Myomatrix arrays could be used for long-term recordings, including over at least two months after implantation in mice. Overall, this study presents a compelling validation of a novel device for high-quality, large-scale, long-term motor unit recordings in a broad range of applications.
Investigating how the nervous system controls movement often requires large-scale recordings from the motor unit population. For example, it is still unclear to what extent the brain has the flexibility to voluntarily recruit individual motor units. Under typical experimental conditions, motor units are normally activated in a fixed order as force increases, from the smallest motoneurons to the largest (Henneman et al., 1965). Even with significant training and effort, human subjects have difficulty reversing this recruitment order voluntarily, and activating larger units while suppressing smaller ones (Bräcklein et al., 2022). However, recent work in nonhuman primates suggests that the motor cortex may be capable of independently controlling individual motor units in certain contexts (Marshall et al., 2022). Recent advances in electrode design, such as the Myomatrix arrays described by Chung et al., are expected to accelerate our understanding of flexible recruitment and other major research questions in the coming years.
References
-
The neural control of movement: a century of in vivo motor unit recordings is the legacy of Adrian and BronkThe Journal of Physiology 7:JP285319.https://doi.org/10.1113/JP285319
-
Functional significance of cell size in spinal motoneuronsJournal of Neurophysiology 28:560–580.https://doi.org/10.1152/jn.1965.28.3.560
-
ConferenceHigh-performance flexible microelectrode array with PEDOT:PSS coated 3D micro-cones for electromyographic recordingAnnual International Conference of the IEEE Engineering in Medicine and Biology Society. pp. 5111–5114.https://doi.org/10.1109/EMBC48229.2022.9871052
-
Flexible neural control of motor unitsNature Neuroscience 25:1492–1504.https://doi.org/10.1038/s41593-022-01165-8
-
Multi-channel intramuscular and surface EMG decomposition by convolutive blind source separationJournal of Neural Engineering 13:026027.https://doi.org/10.1088/1741-2560/13/2/026027
-
Remarks on some aspects of reflex inhibitionProceedings of the Royal Society of London. Series B. 97:519–545.
-
Flexible multielectrode arrays with 2-D and 3-D contacts for in vivo electromyography recordingIEEE Transactions on Components, Packaging, and Manufacturing Technology 10:197–202.https://doi.org/10.1109/tcpmt.2019.2963556
Article and author information
Author details
Britton A Sauerbrei
Publication history
Copyright
© 2024, Kirk and Sauerbrei
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,011
- views
-
- 86
- downloads
-
- 0
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Electromyography: Accessing populations of motor units
eLife 13:e94764.
https://doi.org/10.7554/eLife.94764
Further reading
-
- Neuroscience
Synaptic heterogeneity is a hallmark of nervous systems that enables complex and adaptable communication in neural circuits. To understand circuit function, it is thus critical to determine the factors that contribute to the functional diversity of synapses. We investigated the contributions of voltage-gated calcium channel (VGCC) abundance, spatial organization, and subunit composition to synapse diversity among and between synapses formed by two closely related Drosophila glutamatergic motor neurons with distinct neurotransmitter release probabilities (Pr). Surprisingly, VGCC levels are highly predictive of heterogeneous Pr among individual synapses of either low- or high-Pr inputs, but not between inputs. We find that the same number of VGCCs are more densely organized at high-Pr synapses, consistent with tighter VGCC-synaptic vesicle coupling. We generated endogenously tagged lines to investigate VGCC subunits in vivo and found that the α2δ–3 subunit Straightjacket along with the CAST/ELKS active zone (AZ) protein Bruchpilot, both key regulators of VGCCs, are less abundant at high-Pr inputs, yet positively correlate with Pr among synapses formed by either input. Consistently, both Straightjacket and Bruchpilot levels are dynamically increased across AZs of both inputs when neurotransmitter release is potentiated to maintain stable communication following glutamate receptor inhibition. Together, these findings suggest a model in which VGCC and AZ protein abundance intersects with input-specific spatial and molecular organization to shape the functional diversity of synapses.
-
- Neuroscience
The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small-molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation. DNL343 reduced CNS ISR activity and neurodegeneration in a dose-dependent manner in two established in vivo models – the optic nerve crush injury and an eIF2B loss of function (LOF) mutant – demonstrating neuroprotection in both and preventing motor dysfunction in the LOF mutant mouse. Treatment with DNL343 at a late stage of disease in the LOF model reversed elevation in plasma biomarkers of neuroinflammation and neurodegeneration and prevented premature mortality. Several proteins and metabolites that are dysregulated in the LOF mouse brains were normalized by DNL343 treatment, and this response is detectable in human biofluids. Several of these biomarkers show differential levels in CSF and plasma from patients with vanishing white matter disease (VWMD), a neurodegenerative disease that is driven by eIF2B LOF and chronic ISR activation, supporting their potential translational relevance. This study demonstrates that DNL343 is a brain-penetrant ISR inhibitor capable of attenuating neurodegeneration in mouse models and identifies several biomarker candidates that may be used to assess treatment responses in the clinic.
