A Motor Unit Consists of a Motor Neuron and Multiple Muscle Fibers
The nervous system controls muscle force with signals sent from motor neurons in the spinal cord to the muscle fibers. A motor neuron and the muscle fibers it innervates are known as a motor unit, the basic functional unit by which the nervous system controls movement, a concept proposed by Charles Sherrington in 1925.
A typical muscle is controlled by a few hundred motor neurons whose cell bodies are clustered in a motor nucleus in the spinal cord or brain stem (Figure 34–1). The axon of each motor neuron exits the spinal cord through the ventral root or through a cranial nerve in the brain stem and runs in a peripheral nerve to the muscle. When the axon reaches the muscle, it branches and innervates from a few to several thousand muscle fibers.
A typical muscle consists of many thousands of muscle fibers working in parallel and organized into a smaller number of motor units.
A motor unit consists of a motor neuron and the muscle fibers that it innervates, illustrated here by motor neuron A1. The motor neurons innervating one muscle are usually clustered into an elongated motor nucleus that may extend over one to four segments within the ventral spinal cord. The axons from a motor nucleus exit the spinal cord in several ventral roots and peripheral nerves but are collected into one nerve bundle near the target muscle. In the figure, motor nucleus A includes all those motor neurons innervating muscle A; muscle B is innervated by motor neurons lying in motor nucleus B. The extensively branched dendrites of one motor neuron tend to intermingle with those of motor neurons from other nuclei.
Once synaptic input depolarizes the membrane potential of a motor neuron above threshold, the neuron generates an action potential that is propagated along the axon to its terminal in the muscle. The action potential releases neurotransmitter at the neuromuscular synapse, and this causes an action potential in the sarcolemma of the muscle fibers. A muscle fiber has electrical properties similar to those of a large-diameter, unmyelinated axon, and thus action potentials propagate along the sarcolemma, although more slowly owing to the fiber's higher capacitance. Because the action potentials in all the muscle fibers of a motor unit occur at approximately the same time, they contribute to extracellular currents that sum to generate a field potential near the active muscle fibers.
Most muscle contractions involve the activation of many motor units, whose currents sum to produce signals detected by electromyography. In many instances the electromyogram (EMG) signal is large and can be easily recorded with electrodes placed on the skin over the muscle. The timing and amplitude of EMG activity, therefore, reflect the activation of muscle fibers by the motor neurons. EMG signals are useful for studying the neural control of movement and for diagnosing pathology (see Chapter 14).
In most mature vertebrate muscles each fiber is innervated by a single motor neuron. The number of muscle fibers innervated by one motor neuron, the innervation number, varies with the muscle type and function. In human skeletal muscles it ranges from average values of 5 for an eye muscle to 1,800 for a leg muscle (Table 34–1). Because the innervation number denotes the number of muscle fibers within a motor unit, differences in innervation number indicate differences in the average increment in force that occurs each time a motor unit in the same muscle is activated. Thus the innervation number also indicates the fineness of control of the muscle; the smaller the innervation number, the finer the control achieved by varying the number of activated motor units.
Table 34–1Innervation Numbers in Human Skeletal Muscles ||Download (.pdf) Table 34–1 Innervation Numbers in Human Skeletal Muscles
|Muscle ||Alpha motor axons ||Muscle fibers ||Innervation number |
|Biceps brachii ||774 ||580,000 ||750 |
|Brachioradialis ||333 ||>129,200 ||>410 |
|Cricothyroid ||112 ||18,550 ||155 |
|Gastrocnemius (medial) ||579 ||1,042,000 ||1,800 |
|Interossei dorsales (1) ||119 ||40,500 ||340 |
|Lumbricales (1) ||96 ||10,269 ||107 |
|Masseter ||1,452 ||929,000 ||640 |
|Opponens pollicis ||133 ||79,000 ||595 |
|Platysma ||1,096 ||27,100 ||25 |
|Posterior cricoarytenoid ||140 ||16,200 ||116 |
|Rectus lateralis ||4,150 ||22,000 ||5 |
|Temporalis ||1,331 ||1,247,000 ||936 |
|Tensor tympani ||146 ||1,100 ||8 |
|Tibialis anterior ||445 ||272,850 ||613 |
|Transverse arytenoid ||139 ||34,470 ||247 |
Not all motor units in a muscle have the same innervation number. Indeed, the differences can be substantial. For example, motor units of the first dorsal interosseous muscle of the hand have innervation numbers ranging from approximately 21 to 1,770. Consequently, the strongest motor unit in the hand's first dorsal interosseous muscle can exert about the same force as the average motor unit in the leg's medial gastrocnemius muscle.
The muscle fibers of a single motor unit are distributed throughout the muscle and intermingle with fibers innervated by other motor neurons. The muscle fibers of a single motor unit can occupy from 8% to as much as 75% of the volume in a limb muscle, with 2 to 5 muscle fibers per 100 belonging to the same motor unit. Therefore the muscle fibers in a given volume of muscle belong to 20 to 50 different motor units. This distribution changes with age and with some neuromuscular disorders. For example, muscle fibers lose their innervation after the death of a motor neuron and can be reinnervated by collateral sprouts from neighboring axons.
In some muscles the fibers of motor units are confined to discrete compartments that correspond to the regions of the muscle supplied by the primary branches of the muscle nerve. Selective activation of different compartments that exert forces in different directions provides a biomechanical advantage. Branches of the median and ulnar nerves in the forearm, for example, innervate distinct compartments in three multitendon extrinsic hand muscles that enable the fingers to be moved relatively independently. A muscle can therefore consist of several functionally distinct regions.
The Properties of Motor Units Vary
The force exerted by a muscle depends not only on the number of motor units that are activated during a contraction but also on three properties of those motor units: contraction speed, maximal force, and fatigability. These properties are assessed by examining the force exerted by individual motor units in response to variations in the number and rate of evoked action potentials.
The response to a single action potential is known as a twitch contraction. The time it takes the twitch to reach its peak force, the contraction time, is one measure of the contraction speed of the muscle fibers that comprise a motor unit. Slow-twitch motor units have long contraction times; fast-twitch units have shorter contraction times. A rapid series of action potentials elicits superimposed twitches known as a tetanic contraction or tetanus.
The force exerted during a tetanic contraction depends on the extent to which the twitches overlap and summate: The force varies with the contraction time of the motor unit and the rate at which the action potentials are evoked. At lower rates of stimulation the ripples in the tetanus denote the peaks of individual twitches (Figure 34–2A). The peak force achieved during a tetanus varies as a sigmoidal function of action potential rate, with the shape of the curve depending on the contraction time of the motor unit (Figure 34–2B). Maximal force is reached at different action potential rates for fast-twitch and slow-twitch motor units and is often greater in fast-twitch units.
The force exerted by a motor unit varies with the rate of the action potentials.
A. Traces show the forces exerted by fast- and slow-twitch motor units in response to a single action potential (top trace) and a series of action potentials (set of four traces below). The time to the peak twitch force, or contraction time, is briefer in the fast-twitch unit. The rates of the action potentials used to evoke the tetanic contractions ranged from 17 to 100 Hz in the slow-twitch unit to 46 to 100 Hz in the fast-twitch unit. The peak force for the 100 Hz tetanus is greater in the fast-twitch unit. Note the different force scales for the two sets of traces. (Adapted with permission from Botterman et al. 1986; Fuglevand, Macefield, and Bigland-Ritchie 1999; and Macefield, Fuglevand, and Bigland-Ritchie 1996.)
B. Relation between peak force and the rate of action potentials for fast- and slow-twitch motor units. The absolute force (left plot) is greater for the fast-twitch motor unit at all frequencies. At lower stimulus rates (right plot) the force evoked in the slow-twitch motor unit summed to a greater relative force (longer contraction time) than in the fast-twitch motor unit (briefer contraction time).
The functional properties of motor units vary across the population and between muscles. At one end of the distribution motor units have long twitch contraction times and produce small forces, but are difficult to fatigue. These motor units are the first activated during a voluntary contraction. In contrast, the last motor units activated have short contraction times, produce large forces, and are easy to fatigue. As observed by Jacques Duchateau and colleagues, most human motor units produce low forces and have intermediate contraction times (Figure 34–3).
Distributions of motor unit properties.
(Reproduced, with permission, from Van Cutsem et al. 1997.)
A. Distribution of twitch torques for 528 motor units in the tibialis anterior muscle.
B. Distribution of twitch contraction times for 528 motor units in the tibialis anterior muscle.
Because these contractile properties of a motor unit depend on the characteristics of its muscle fibers, we can distinguish different types of muscle fibers. This distinction stems from structural specializations and differences in the metabolic properties of muscle fibers. All muscle fibers belonging to a motor unit have similar biochemical and histochemical properties.
One commonly used scheme distinguishes muscle fibers by their reactivity to histochemical assays for the enzyme myosin adenosine triphosphatase (ATPase), which is used as an index of contractile speed. Based on histochemical stains for myosin ATPase, it is possible to identify type I and type II muscle fibers. Slow contracting motor units contain type I muscle fibers, and fast contracting units include type II fibers. The type II fibers can be further classified into the least fatigable (type IIa) and most fatigable (type IIb, IIx, or IId). Another commonly used scheme distinguishes muscle fibers on the basis of genetically defined isoforms of the myosin heavy chain. Those in slow contracting motor units express myosin heavy chain-I, those in fast contracting and least fatigable units express myosin heavy chain-IIa, and fibers in fast contracting and most fatigable units express myosin heavy chain-IIb or -IIx. There is a high degree of correspondence between the two classification schemes for muscle fibers.
Physical Activity Can Alter Motor Unit Properties
Alterations in habitual levels of physical activity can influence the three contractile properties of motor units (contraction speed, maximal force, and fatigability). A decrease in muscle activity, such as occurs with aging, bed rest, limb immobilization, or space flight, reduces the maximal capabilities of all three properties. The effects of increased physical activity depend on the intensity and duration of the activity. Brief sets of high-intensity contractions performed a few times each week can increase contraction speed and motor unit force, whereas prolonged periods of low-intensity contractions can reduce motor unit fatigability. Physical activity regimens that involve such differences are often described as strength training and endurance training, respectively.
Changes in the contractile properties of motor units involve adaptations in the structural specializations and biochemical properties of muscle fibers. The improvement in contraction speed caused by strength training, for example, is associated with an increase in the maximal shortening velocity of a muscle fiber caused by the enhanced capabilities of the myosin molecules in the fiber. Similarly, the increase in maximal force is associated with the enlarged size and increased intrinsic force capacity of the muscle fibers produced by an increase in the number and density of the contractile proteins.
In contrast, alterations in the fatigability of a muscle fiber can be caused by many different adaptations, such as changes in capillary density, the number of mitochondria, excitation-contraction coupling, and the metabolic capabilities of the muscle fibers. Endurance exercise can promote the biogenesis of mitochondria and enhance the oxidative capacity of a muscle fiber, thereby reducing its fatigability. Although the adaptive capabilities of muscle fibers decline with age, the muscles remain responsive to exercise even at 90 years of age.
Despite the efficacy of strength and endurance training in altering the contractile properties of muscle fibers, these training regimens have little effect on the composition of a muscle's fibers. Although several weeks of exercise can change the proportion of type IIa and IIx fibers, there is no change in the proportion of type I fibers. All fiber types adapt in response to exercise, although to varying extents depending on the type of exercise. For example, strength training of leg muscles for 2 to 3 months can increase the cross-sectional area of type I fibers by 0% to 20% and of type II fibers by 20% to 60%, increase the proportion of type IIa fibers by approximately 10%, and decrease the proportion of type IIx fibers by a similar amount. Furthermore, endurance training may increase the enzyme activities of oxidative metabolic pathways without noticeable changes in the proportions of fiber types, but the relative proportions of type IIa and IIx fibers do change as a function of the duration of each exercise session. Conversely, several weeks of bed rest or limb immobilization do not change the proportions of fiber types in a muscle, but they do decrease the size and intrinsic force capacity of muscle fibers.
Although physical activity has little influence on the proportion of type I fibers in a muscle, more substantial interventions can have an effect. Space flight, for example, exposes muscles to a sustained decrease in gravity, reducing the proportion of type I fibers in leg muscles. A few weeks of continuous electrical stimulation at a low frequency causes a marked increase in the proportion of type I fibers and a substantial decrease in fiber size. Similarly, surgically changing the nerve that innervates a muscle alters the pattern of activation; eventually the muscle exhibits properties similar to those of the muscle that was originally innervated by the transplanted nerve. Connecting a nerve that originally innervated a rapidly contracting leg muscle to a slowly contracting leg muscle, for example, will cause the slower muscle to become more like a faster muscle.
Muscle Force Is Controlled by the Recruitment and Discharge Rate of Motor Units
The force exerted by a muscle during a contraction depends on the number of motor units that are activated and the rate at which each of the active motor neurons discharges action potentials. Force is increased during a muscle contraction by the activation of additional motor units, which are recruited progressively from the weakest to the strongest (Figure 34–4). A motor unit's recruitment threshold is the force during the contraction at which the motor unit is activated. Muscle force decreases gradually by terminating the activity of motor units in the reverse order from strongest to weakest.
Motor units that exert low forces are recruited before those that exert greater forces.
(Adapted, with permission, from Desmedt and Godaux 1977 and from Milner-Brown, Stein, and Yemm 1973.)
A. Action potentials in two motor units were recorded concurrently with a single intramuscular electrode while the subject gradually increased muscle force. Motor unit 1 began discharging action potentials near the beginning of the voluntary contraction, and its discharge rate increased during the contraction. Motor unit 2 began discharging action potentials near the end of the contraction.
B. Average twitch forces for motor units 1 and 2 as extracted with an averaging procedure during the voluntary contraction.
C. The plot shows the forces at which 64 motor units in a hand muscle of one person were recruited (recruitment threshold) during a voluntary contraction versus the twitch forces of the motor units.
The order in which motor units are recruited is highly correlated with several indices of motor unit size, including the size of the motor neuron cell bodies, the diameter and conduction velocity of the axons, and the amount of force that the muscle fibers can exert. Because the recruitment threshold of a motor unit depends on the membrane resistance of the motor neuron, which is inversely related to its surface area, a given synaptic current will produce larger changes in the membrane potential of small-diameter motor neurons. Consequently, increases in the net excitatory input to a motor nucleus cause the levels of depolarization to reach threshold in an ascending order of motor neuron size: The smallest motor neuron is recruited first and the largest motor neuron last (Figure 34–5). This effect is known as the size principle of motor neuron recruitment, a principle enunciated by Elwood Henneman in 1957.
The response of a motor neuron to synaptic input depends on its size.
Two motor neurons of different sizes have the same resting membrane potential (Vr) and receive the same excitatory synaptic current (Isyn) from a spinal interneuron. Because the small motor neuron has a smaller surface area, it has fewer parallel ion channels and therefore a higher resistance (Rhigh) . According to Ohm's law (V = IR,), Isyn in the small neuron produces a large excitatory postsynaptic potential (EPSP) that reaches threshold, resulting in the discharge of an action potential. The small motor neuron has a small-diameter axon that conducts the action potential at a low velocity (vslow) to fewer muscle fibers. In contrast, the large motor neuron has a larger surface area, which results in a lower transmembrane resistance (Rlow) and a smaller EPSP that does not reach threshold in response to Isyn.
The size principle has two important consequences for the control of movement by the nervous system. First, the sequence of motor-neuron recruitment is determined by spinal mechanisms and not by higher regions of the nervous system. This means that the brain cannot selectively activate specific motor units. Second, motor units are activated in order of increasing fatigability, so the least fatigable motor units available produce the initial force required for a specific task.
As suggested by Edgar Adrian in the 1920s, the muscle force at which the last motor unit in a motor nucleus is recruited varies between muscles. In some hand muscles all the motor units have been recruited when the force reaches approximately 60% of maximum during a slow muscle contraction. In the biceps brachii, deltoid, and tibialis anterior muscles, recruitment continues up to approximately 85% of the maximal force. However, because the recruitment threshold of motor units decreases with contraction speed, during a rapid contraction most motor units in a muscle are recruited with a load of approximately 33% of maximum. Beyond the upper limit of motor unit recruitment, muscle force can still be increased by varying the rate of action potentials in the motor neurons. Below the upper limit of recruitment, the rate of firing can also be varied in addition to increasing the number of active motor units (Figure 34–6). In fact, beneath the upper recruitment limit variation in discharge rate can have the greater influence on muscle force.
Muscle force can be adjusted by varying the number of active motor units and their discharge rate.
A gradual increase and then a decrease in the force (blue line) exerted by the knee extensor muscles involved the concurrent activation of four (out of many) motor units. The muscle force was changed by varying both the number of motor units that were active and the rate at which the motor neurons discharged action potentials. Motor unit 1 was activated when muscle force reached 20% of maximum. Initially the motor neuron discharged action potentials at a rate of 9 Hz. As force increased, the discharge rate increased up to 15 Hz, when both the force and discharge rate declined, and the motor unit was inactivated at 14% of maximal force. Motor units 2, 3, and 4 were activated at greater forces but discharge rate was modulated similarly. (Reproduced, with permission, from Person and Kudina 1972.)
The Input–Output Properties of Motor Neurons Are Modified by Input from the Brain Stem
The discharge rate of motor neurons depends on the magnitude of the depolarization generated by excitatory inputs and the intrinsic membrane properties of the motor neurons in the spinal cord. These properties can be profoundly modified by input from monoaminergic neurons in the brain stem. In the absence of this input, the dendrites of motor neurons passively transmit synaptic current to the cell body, resulting in a modest depolarization that immediately ceases when the input stops. Under these conditions the relation between input current and discharge rate is linear over a wide range.
The input–output relation becomes nonlinear, however, when the monoamines serotonin and norepinephrine activate L-type Ca2+ channels on the dendrites of the motor neurons. The resulting inward Ca2+ currents can enhance synaptic currents by five- to tenfold (Figure 34–7). In an active motor neuron this enhanced current can sustain an elevated discharge rate after a brief depolarizing input, a behavior known as self-sustained firing. A subsequent brief inhibitory input at a low velocity returns the discharge rate to its original value.
Effects of monoaminergic input on motor neurons.
(Data from C. J. Heckman.)
A. Membrane currents and potentials in spinal motor neurons of adult cats that were either deeply anesthetized (low monoaminergic drive) or decerebrate (moderate monoaminergic drive). When monoaminergic input is absent or low, a brief excitatory input produces an equally brief synaptic current during voltage clamp (upper record). This current is not sufficient to bring the membrane potential of the cell to threshold for discharging action potentials (lower record). During high levels of monoaminergic input the same brief excitatory input activates a persistent inward current in the dendrites, which amplifies the synaptic current and generates a long-lasting tail current (upper record). This persistent inward current causes a high discharge rate during the input and the tail current sustains the discharge after the input ceases (lower record). A brief inhibition will return the cell to the resting state.
B. With high levels of monoaminergic input the persistent inward current produces a much higher discharge rate for a given amount of current.
C. When the entire motor pool innervating a muscle is considered, the monoamine-induced increase in the rate of motor neuron discharge produces a much larger force for a given amount of input and maximal force is achieved with less input to the motor neuron pool.
Because the properties of motor neurons are strongly influenced by monoamines, the excitability of the pool of motor neurons innervating a single muscle is under control of the brain stem. Moderate monoaminergic input to the motor neurons of slow contracting motor units promotes self-sustained firing. This is probably the source of the sustained force exerted by slower motor units to maintain posture. During sleep, when monoaminergic drive is withdrawn, excitability decreases, thus helping to ensure a relaxed motor state. Monoaminergic input from the brain stem can adjust the gain of the motor unit pool to suit the demands of different tasks. This flexibility does not compromise the size principle of orderly recruitment because the threshold for activation of the persistent inward currents is lowest in the motor neurons of slower motor units, which are the first recruited even in the absence of monoamines.