The Centennial of the Motor Unit and Sir Charles Scott Sherington

The motor unit (MU) is the fundamental building block of the nervous system related to motor function. From a descriptive perspective, we can describe it as the structure that includes the alpha motor neuron’s cell body, dendrites, as well as the axon from the apex region and all the muscle fibers it innervates. It is a structure formed by the union of two anatomically distinct structures: muscle fibers and neurons located in the anterior horn of the medulla spinalis. Understanding this distinct cellular structural partnership, which must be evaluated functionally together, is crucial for understanding and studying the characteristics of motor ability and its diseases.[1] Historically, understanding this functional unity of the MU has been possible primarily through understanding its constituent components. The process of understanding the components of the MU has followed a rather complex path. The beginnings of the scientific understanding of the motor neuron can be traced back to pioneers in the 1820s. François Magendie and Sir Charles Bell defined the Bell-Magendie law, which established the relationship between the anterior roots and motor functions. The realization that dorsal roots were linked to sensory functions represented another crucial step in the functional anatomy of the nervous system. This initial approach necessitated the development of the “neuron hypothesis,” which defined neurons as distinct cell structures. Almost half a century later, Santiago Ramon Y Cajal received the Nobel Prize in 1906, completing the identification of these cellularly differentiated nervous system structures.[2] The establishment of the functional link between motor neurons and muscle fibers was achieved through the contributions of physiologists, and we owe this to Sir Charles Scott Sherington[1] [Figure 1]. In 1925, in his article, “Remarks on some aspects of reflex inhibition,” published in Proc R Soc Lond B Biol Science, he defined the term “MU” for the first time as “the entire axon of the motor neuron, from its perikaryon crest to its terminals within the muscle, along with its muscle fibers.”[3] It was not until 100 years after discovering the link between anterior roots and motor functions that the idea of the MU was finally established. In the words of Eric Kugelber, “He introduced the concept of the MU…and made clear how important a structure it was, the functional entity which forms the bases of all grading of muscle contraction. Sherrington had never the opportunity actually to see the MU.”[4]Figure 1: Charles Scott Sherrington; English neurophysiologist. November 27, 1857 – March 4, 1952We are celebrating the 100th anniversary of this term, defined in 1925.[1] This important step in neuroscience, crowned with a Nobel Prize, deserves to be properly commemorated, and the purpose of this article is to express this appreciation in its own right. Sherrington’s first law describes the posterior roots supplying a specific area of skin through a specific overlap of adjacent dermatomes. Thus, the functionality of the anterior and posterior roots reached the level of contemporary understanding. Sherrington’s second law describes reciprocal innervation in relation to reflex mechanisms, defining the existence of inputs related to the excitation of a muscle contraction and the inhibition of the antagonist muscle, and the necessary connection for understanding the mechanisms underlying coordinated movements.[5] These developments are part of the path leading to the concept of the final common pathway and define the central role of alpha motor neurons in muscle contraction. All these steps earned Sir Charles Scott Sherington, along with Edgar Gouglas Adrian, the Nobel Prize in 1932.[6] It is natural that the Nobel Prize was awarded “for their discoveries regarding the functions of neurons.” It is clear that the cornerstone of this process was the identification of the MU. Indeed, the identification of subgroups of motor neurons by distinguishing them based on their size differences, establishing their functional relationships, and so on, was all successive developments. The steps taken between 1940 and 1950 regarding the components of the MU provided the insight that earned Eccles the Nobel Prize in 1963 and Ragnar Granit the Nobel Prize in 1967. It is worth noting that this process was advanced by the contributions of numerous scientists. The contributions of Matthews, Erlanger, Bishop, Gasser, Lundberg, Jankowska, Hultborn, Kernell, and Housgaard in identifying the components of the motor system and deciphering the details of motor control are noteworthy.[2] FROM MOTOR UNIT TO MOTOR UNIT POTENTIAL The transition from the concept of the MU to MU potential (MUP) occurred during this historical process. The first clear definition of the MUP is found in Weddell and Pattle’s 1941 study entitled “Demonstration of Apparatus for Recording Muscle and Nerve Action Potentials.”[7] In their article, they stated that muscle action potentials were recorded using the concentric needle electrode developed by Brown in 1937. In normal cases, muscle action potentials were measured using a concentric needle electrode. They defined the potentials they observed as “MU action potentials” (MUAPs). The discharge frequency and morphologic characteristics of the potentials, their appearance under normal and pathologic conditions, are described in detail, and similarities are cited in previous studies by Lindsley and Hoefer and Putnam.[7] The article describes all the characteristics of the MUP, which are similar to our current understanding. It was clearly defined that the potentials obtained by MU activity and recorded from muscles with needle electrodes are due to action potentials in muscle fibers. However, considering that there is not a single action potential belonging to the MU, but rather a potential representing it depending on the position of the needle, the term MUAP is questionable. We owe the definition of the potential recorded from muscle with needle electrodes as MUP to Buchthal [Figure 2]. The potential generated by the sum of the action potentials generated by each muscle fiber of a MU is called the MUP. This is the most appropriate definition, both morphologically and physiologically, as well as for clinical application.[8] Buchthal defined the MU as “the MU originates from the summed action potentials of all fibers of the MU.”[9]Figure 2: Fritz Buchthal; German-Danish neurophysiologist. August 19, 1907–December 24, 2003The definition of the MU with its basic properties was achieved in 1925, and approximately 25 years later, the MUP, representing the MU, was reached. Although the terminology of MUAP is used synonymously, it should be accepted that the term MUP is a more accurate expression because it shows the sum of the action potentials generated by the muscle fibers innervated by the MU on the recording electrode, rather than the potential of the MU itself, as in the muscle fiber [Figure 3].Figure 3: Schematic representation of the anatomical and physiological basis underlying the recording of motor unit potential with a concentric needle electrode. (Reproduced from Cumhur Ertekin’s book Central electromyography, with permission of the author.)A century has passed since Sharrington’s identification of the MU, the fundamental movement unit of the nervous system, and the needle electrode remains an indispensable tool in our recording system, as it is still a valuable tool in studying MUPs and understanding changes in diseases. The identification of motor neuron subgroups, the identification of alpha, gamma, and beta motor neurons, and the recognition that the alpha motor neuron is further subdivided into fast, slow, and intermediate forms, have been crucial steps in understanding the intricacies of motor control.[2] Alpha-fast, alpha-fatigue-resistant, and alpha-slow subgroups also determine the physiologic, mechanical, and pathologic properties of the muscle fibers they innervate. Alpha-slow motor neurons are motor neurons of Group I muscle fibers and predominate in muscles requiring endurance, and alpha-fast, alpha-fatigue-resistant motor neurons are motor neurons of Group II muscle fibers and are more prevalent in muscles used in phasic activity.[10] Since Sherrington, our understanding of the final common pathway has evolved significantly. Meticulous studies have shown that motor neurons innervate numerous muscle targets with a well-organized plan, resulting in the creation of a heterogeneous functional motor neuron population. Although we still have a long way to go, the concept of the MU deserves to be remembered in its centennial year, a year filled with excitement and awards.