Learning Objectives
By the end of this section, you should be able to
- 10.2.1 Distinguish between upper and lower motoneurons and explain the concept of a motor unit in this context.
- 10.2.2 Enumerate the components of the neuromuscular junction with roles for the basal laminae, junctional folds, acetylcholinesterase, and nicotinic receptors.
- 10.2.3 Explain the basis of classic myasthenia gravis and how it compromises muscle activity.
- 10.2.4 Explain the two processes by which force can be increased based on LMN activity and why the more complex “recruitment of more” follows the size principle to elevate force.
- 10.2.5 Describe special organizations and locations in the spinal cord supporting key LMN distributions in ventral grey in relation to limbs and body parts.
- 10.2.6 Describe what central pattern generation means and how this activity is somewhat like, yet somewhat different from, reflex circuitry.
- 10.2.7 Explain the basis of proprioceptive feedback from spindle fibers and Golgi tendon organs and how those systems integrate into reflex control of movement by exerting lower-level control at the spinal level.
Neuroscientists divide the motor system into lower levels and upper levels for clinical purposes. The implementation of final contractions occurs at lower, output levels, while the organization of what to do when (given current circumstances) occurs at upper CNS levels privy to sensations and goals. Distinct body parts are organized in cortical regions described as primary motor (M1) which sends most of the motor commands into descending axon tracts that eventually inform the posterior spinal and brainstem regions and their reflex-related circuitry how we desire to behave. The M1 area is not the only region capable of engaging major movement decisions. Therefore, all neurons making up regions that typically reside in higher or more rostral locations and coordinate the decisions to move based on decision-making circuitry are called upper motor neurons (UMNs). By contrast, all neurons that reside in more caudal brainstem or spinal regions and project directly to synapse on muscles are referred to as lower motor neurons (LMNs). LMNs implement the contractions due to their contact with muscles, and UMNs essentially decide when to engage or which muscles to engage to accomplish an inspired goal.
This section focuses on the LMN system, discussing the mechanisms associated with LMN activation of muscles. LMNs take care of lower implementation. They are defined as all motor neurons extending from the central nervous system (typically the brainstem and spinal cord) and directly connecting with effector muscles. In this section, we will be discussing how LMNs are organized, how their activity drives muscles, and what are the reflexive feedback mechanisms allowing for local control and reflexes. We will discuss the upper levels of control in the following section.
LMN organization
Spinal cord LMNs are responsible for most of our limb and trunk movements. Within the spine, local LMNs reside in the ventral (bottom or stomach-facing) portion of an H-like overall structure comprising the middle portion of the spine. The dorsal (upper or back-facing) portion of spinal grey contains intermediate neurons responsible for relaying sensory information (see Figure 10.8). Importantly, the ventral region of this spinal grey is organized somatotopically in relation to the outer body, so medially located LMNs control medial trunk musculature, and lateral LMNs near limbs control the limb joints progressively (shoulder → elbow → wrist → fingers most lateral).
Moving our heads involves LMNs within various brainstem nuclei, which target our face, eyes, tongue, and other such movements via cranial nerves exiting specific skull foramen (special holes, see Figure 10.9).
LMNs activate the neuromuscular junction
LMN synapses on muscle fibers occur through neuromuscular junctions (NMJs, Figure 10.5). NMJs from the axon collaterals of a single LMN are activated simultaneously within muscle masses, larger motor units activating more, and smaller less, yielding differential force. Within the NMJ, activated LMN axon terminals release ACh across the synaptic gap and through a leaky surrounding protein matrix encompassing muscle cells called the basal laminae, and onto the postsynaptic surface of a muscle fiber (sarcomere arrangement, see Figure 10.2 and this animation). A motor unit, as was introduced in 10.1 The Physiological Actions Implementing Movement – Contraction of Muscles, is a LMN and all the individual muscle fibers it synapses on. Smaller motor units activate fewer muscle fibers. They get activated in the early movement stages until more force becomes necessary for the current load. Then larger motor units are recruited.
Skeletal muscle ACh receptors, called nicotinic receptors, are ionotropic. When ACh from the LMN presynaptic terminal binds to these nicotinic ACh receptors on muscles, it creates immediate depolarization. Bound and opened nicotinic channels transmit cations across the sarcolemma and depolarize the muscle fiber, triggering action potentials. These receptor constructs reside on top of waves or ridges in the postsynaptic membrane called junctional folds, placing the receptors near the source of ACh travelling across the synapse. ACh remains only briefly after release from motoneurons. Efficient enzymes called acetylcholinesterase residing in the basal laminae (within the synapse; see Figure 10.5) quickly break it down into choline and the acetyl group, preventing perpetual stimulation disconnected from motoneuron activations (see Chapter 3 Basic Neurochemistry). More force (e.g., greater muscle contraction) can be coaxed from the activated muscle fibers if the LMN is driven to higher action potential frequencies. Resulting increased ACh will maintain and intensify the cycling and power stroking activity within the fibers.
Problems from Myasthenia Gravis
The autoimmune disease myasthenia gravis significantly interferes with ACh effectiveness in generating muscle action potentials. In its classic form, disruptive antibodies are produced that destroy nicotinic receptors by binding-up their protein components. This diminishes the numbers of binding receptors, so the typical release from one LMN action potential becomes inadequate. This loss of ACh effectiveness delays muscle contraction and disrupts the coordination between contractions triggering actions. The end result is slow/jerky movement or sometimes no movement when patients attempt to move. These negative effects of myasthenia gravis highlight the importance of single LMN synapses per each muscle fiber. Each muscle fiber containing only one neuromuscular junction usually maintains control over when muscles contract. Losing this control also means muscles won’t always activate properly when needed.
Lower motor neurons as motor units and force selection
A key part of controlling the force of muscle contraction is selecting the number and size of motor units to engage. All LMN axon collaterals from a single LMN, whether large or small, target muscle fibers pulling in essentially the same direction. Larger LMNs exhibit thicker and larger axons which innervate more muscle fibers than smaller ones, thereby generating greater pull. We typically start pushing or lifting with smaller motor units, and engage more, larger ones when more force is necessary. We adjust the force required for a task through trial and error. This helps us avoid crushing eggs unintentionally.
Interestingly, larger LMNs require greater intensities of afferent input to reach action potential threshold than smaller. This is because with greater size comes accumulation of leakiness, a phenomenon known as the size principle. When neurons are depolarized towards their threshold for action potential, specific channels open to allow positive charge in. The larger the neuron, the leakier it gets (depolarization doesn't remain in the neuron but quickly dissipates through expansive channels expressed). If a neuron is leaky, activating the motoneuron resembles blowing up a leaky balloon, requiring faster more powerful breath (i.e., faster more powerful descending UMN, stimuli) (see Chapter 2 Neurophysiology ).
This set-up, with larger more leaky and smaller less leaky LMNs, is ideal for recruiting motor units. Descending control, where conscious decisions are engaged, derives from the UMNs (to be discussed in the next section). To activate smaller motor units, only small descending UMN activations are necessary, typically occurring with a new effort of unknown load. However, if the load is larger than anticipated, larger motor units are needed. The system needs to adjust to engage more descending input. This size principle gives us control over recruiting these motor units based on how intensely descending UMN stimulation develops because the bigger LMNs need more excitation from upper levels to fire action potentials. Of course, UMNs can also ramp up the activity of already selected LMNs. This descending control governs both mechanisms of force selection introduced in 10.1 The Physiological Actions Implementing Movement – Contraction of Muscles.
Central pattern generators
Many of the motor, sensory and inter-neurons in the spinal grey are part of central pattern generation . Central pattern generator (CPG) circuits at the spinal cord level coordinate patterns of back-and-forth movements. The circuits supporting these patterns are largely pre-wired to activate locomotion limb flexor and extensor groups, so quadruped animals can maintain patterns of walking → faster walking → trotting → running without lots of descending corticospinal UMN management (Collins and Richmond, 1994). These pattern generators exhibit sophisticated use of inhibitory interneurons, ensuring up and out limb movement is not compromised by muscles pulling the body forward once the limb lands and holds weight. Descending UMNs appear necessary for balance and coordinating changes of movement speed for bipedal species, and largely for quadruped movement speed changes.
In quadrupeds, these CPGs can maintain walking patterns of limb movements with minimal input from the higher cerebrum/brainstem UMNs. For example, spinal transected cats can maintain walking responses across all four limbs on a treadmill without any contributions from the cerebrum (Côté et al., 2003). Two leg walking (i.e., in bipedal species like humans), in contrast, requires additional, significantly greater contributions from balance control systems in the upper motor systems. People with spinal cord injuries, like the late Christopher Reeve, cannot therefore self-generate walking patterns and must use wheelchairs for life. Interestingly, there have been efforts to create external load-bearing and balancing hybrid assistive limb exoskeletons which redirect rehabilitation to the patient's capacity for voluntary motion, and signs point to far greater success potential with these systems than when patients attempt to recover balance on their own, unsupported (Aach et al., 2014). These data suggest that human bipedal walking still benefits from intact spinal CPGs, and evidence also indicates that we utilize CPGs regularly so that we can walk alongside friends and concentrate on our conversations rather than where our feet land (Dimitrijevic et al., 2006; Klarner and Zehr, 2018). Another bit of evidence for CPGs in humans occurs just prior to infants' first walking, when descending control from upper level UMNs is limited, but their back-and-forth "walking" motions nevertheless occur so long as the infant is held. These walking motions when supported are observed far in advance of the infant establishing walking. The balance needed for weight-bearing walking seems to come later and is what is missing after human spines are injured (Minassian et al., 2017).
The feedback proprioceptive senses
Before discussing reflex intricacies, we need to describe the proprioceptive sense mechanisms. These mechanisms are technically sensory, but they are also an integral part of movement control (see Chapter 9 Touch and Pain). Through these sensors we monitor body or limb positions by the degree of muscle stretch (width of smile or extension of arms) and muscle load, or tension, intensity – even the load of our bodies on our legs.
The sensors for muscle stretch are called spindle fibers or muscle spindles. They are activated by mechanical pull to signal either whether a stretch has occurred, or at what rate stretch is occurring. The sensors for muscle tension, or the loads muscles attempt to counteract, are called Golgi tendon organs. Golgi tendon organs are activated by how much collagen fibers constituting the tendons squeeze down on the terminal sensory endings interwoven among collagen fibers. Their activation therefore reflects the extent of opposing pull between muscle and load. Together, these senses represent proprioception – a self-awareness of where our body is and the forces necessary to get it there.
The Disembodied Lady
To grasp how much we use proprioception, consider the story by Oliver Sacks in “The Man Who Mistook His Wife for a Hat and other Clinical Tales” (1987). In the essay The Disembodied Lady within this book, Sacks reports the horrible circumstances of a life limited due to damage in proprioception-processing regions. The woman he described felt that she was living in an essentially dead body. For example, she had to guide her limbs into place with visual confirmation while dancing because she could not feel her body movements as intentional. Imagine anyone who appreciates the elegance of ballet having that feeling of movement “rightness” snatched away! The integration between contractions engaged and the feeling that contractions are moving us where we intended, provided by proprioception, is critical in supporting the implicit feeling in which we’re doing what we intended to do, and are doing it right. As we describe these mechanisms of proprioception, keep in mind some sensory information is utilized only within lower levels to support unconscious reflex adjustments, while other information goes to upper levels for conscious (explicit) realization to produce the “feeling” lost by this disembodied lady.
The Muscle Spindles and related reflexes
Muscle spindles are also called spindle fibers, or generally, stretch receptors (see Figure 10.10). To appreciate the function of these receptors, think about kicking a soccer ball at different speeds. Kicking the ball hard requires some momentum in our leg, so we should be able to initially feel our leg further back in space before initiating this swing. The sense of our properly positioned leg comes from stretch signals originating at our leg extensors and hip flexors. The sensory information from muscle spindles let us focus our eyes on finding the goal or teammates rather than looking at our legs during the match.
Proprioception via muscle spindles relies on intrafusal muscle fibers, which are different than the force producing and contracting muscle fibers (discussed in the previous section about contraction strategy) that we can now call extrafusal fibers by comparison. Both intrafusal and extrafusal fibers extend in parallel from one tendon to the other. However, they each have different functions and connect to unique classes of LMNs. Extrafusal fibers engage movement/contraction—they are the muscle fibers that generate force. Intrafusal fibers, in contrast, host spindle fiber stretch receptor mechanisms.
Spindles, which include the specialized sensory fibers wrapping around the middle of intrafusal fibers, are key to sensing stretch. When intrafusal fibers are pulled lengthwise, mechanical receptors open within spindles to elicit depolarization, activating their attached sensory fibers (Hunt, 1990).
Stretch response-based reflexes are plentiful within the spinal cord architecture. When a larger muscle is stretched rapidly and unexpectedly, a reflex mechanism involving feedback from the spinal cord snaps the limb back into place. The knee-jerk reflex is prominent among such stretch reflexes (see Chapter 1 Structure and Function of the Nervous System: Cells and Anatomy, shown in Figure 10.11). Many of you have probably experienced your doctor producing this during routine check-ups. To elicit this reflex, a clinician hits just below your kneecap with a rubber hammer, impacting the tendon of your leg extender muscle, causing an unexpected stretch. This extensor stretch excites the spindle sensory fiber, which synapses on and excites alpha motor neurons in the spinal cord, which in turn activates leg extensor contractions. Your leg kicks outward. Doctor: Beware!
You might wonder why we need this reflex. We don't usually hit ourselves in the knee. But imagine yourself on a lurching boat. Your legs attempt to keep you upright, but you can't keep up with the timing of the waves and create anticipatory movements. Luckily, the knee-jerk reflex responds to waves which might make you fall backward, tightening the extensor muscle and pulling your body forward rather automatically. If you spend time on ships where your muscles do this regularly, you develop sea legs (muscular thighs), unaware of the extra exercise while just standing there.
Though reflexes are somewhat self-contained at the spinal cord level, they also rely on upper motor system input for regulation of their strength. This dependence is quite evident when descending UMN control is absent, as in "spinal" injuries severing the descending systems at the brainstem level. Patients with such injuries show large increases in the intensity of reflexes. This hyperreflexia indicates that descending control interacts intimately with reflex circuitry, usually to keep the degree of reflex responses circumscribed to desired levels but also because UMNs often activate general limb motion through synapsing on spinal reflex circuitry (Frigon and Rossignol, 2008; Adams and Hicks, 2005).
Gamma versus alpha motoneuron system
We have described the extrafusal fibers as contracting to generate force/movement, responding to ACh from LMNs to initiate this force when needed to move our bodies. The LMNs activating those extrafusal fibers are called alpha motoneurons. Separate from the alpha motor neuron system is the gamma motor neuron system. The intrafusal fibers are innervated by an LMN population called gamma motoneurons, whose job is to tighten the intrafusal fibers to ensure the spindles remain sensitive. Mechanoreceptors in spindles only open and produce a signal when the spindles are stretched tight, so it's important for mechanisms to maintain tension on the intrafusal fibers. If they slacken, no signal can be generated. To understand this, imagine that a rubber band is representing the spindle fiber. You've made evenly spaced half-centimeter-apart marks along its length, representing the wrapping curls. If you stretch the rubber band, the marks separate. This represents the action causing a signal to be generated by the spindle fiber. Now allow the band to slacken to shorter than its unstretched length. At this point, the marks don't separate and won't until the band is extended to its original pre-stretched length. Mark separation cannot occur again until tightness is restored, visually representing what gamma motoneurons do to intensify stretch perception. They keep our spindle fibers tight and sensitive when this sensitivity is needed.
Figure 10.10 demonstrates how gamma motor neuron firing maintains spindle sensitivity as fibers around them contract. A contraction of the main muscle mass would naturally cause the spindle fibers to go slack and stop sending signals. This loss of tension is rectified by gamma stimulation of contraction and tightening of the intrafusal fibers. The ability to maintain sensitivity to stretch despite muscle contraction is, therefore, derived from coactivation of the alpha and gamma systems at unique moments of need. Interestingly, we don't always co-activate alpha and gamma systems. Quick, thrusting movements like waving away a horsefly or throwing a punch are termed ballistic and differ from our more controlled movements in that the gamma motor system does not co-activate with the alpha motoneurons. Instead, the alpha motoneurons initiate a force vector and simply let it fly without attempting to sense the ongoing movement or slow down the trajectory. The important take-home is gamma motoneuron activity increases sensitivity of stretch perception. It is not involved in producing pulling force to move our bodies.
The Golgi Tendon Organs and related reflexes
As its name implies, the Golgi tendon organ receptor for tension or force produced by muscle contraction is buried within the tendons at either end of skeletal muscles. These receptors sense the tension or force produced by skeletal muscles when contractions pull hard, or the lack of force when pull is weak.
There are Golgi tendon organs in every skeletal muscle tendon. Some muscle tension is more subtle and constant than we might imagine. When we lift a barbell, the force generated is proportional to the weights and effects of gravity on them. Not as intuitive but no less imaginable: holding our body up creates tension in the muscles of our legs.
Instead of a stretch opening mechanical ion channels to cause depolarization, in this receptor, a squeeze induces depolarization. Each tendon is made up of multiple collagen fibers weaving into and through each other. The resulting strong, combined tendon fiber withstands the pull forces placed upon it. Rather than wrapping around a single fiber like spindle fibers, Golgi tendon organs sensory endings weave within the matrix of the tendon’s collagen fibers. Just like fingers are squeezed if inserted between the strands of rope twine pulled tight, these Golgi tendon organ end fibers are squeezed by the force produced by the contraction of the muscle fiber, eliciting firing (Stuart et al., 1972). The experience of dancing with others involves holding hands, lifting, and swinging in ways that we’d rather not be interpreted as “too tight,” “too sudden,” or “too fast.” Being subtle with our touch can also avoid accusations of squeezing parts that perhaps should not be squeezed out of context. Feedback from Golgi tendon organs to our lower motor neurons keeps it soft, appropriate, and “let’s just glide this way.”
Collaboration between grip, touch and stretch
Though we considered spindle and Golgi tendon organs separately above, our movements are constantly informed by their integrated proprioceptive feedback. Proprioceptive guidance of our movements can also be supplemented by input from other sensations, such as our touch receptors (see Chapter 9 Touch and Pain). To appreciate how touch and proprioception come together to inform complex movement, consider how monkeys swing through trees. This activity also involves considerable descending control from UMNs, but for now we can envision what occurs within our current focus on the lower level. Monkeys swing through trees all the time; it's simply part of daily life. But they require sophistication. To succeed, the monkey needs to hold one branch until it has sufficient grip to switch its body weight to the next branch. Then, it needs to release the previous branch in time with the swing, so it doesn't get stuck holding two branches (awkward). The primate needs a pattern of swing-grab-tighten-hold-let-go. Let's look at all the sensory components needing to be coordinated (Zimny et al., 1989; Lephart et al., 1998; Gilman, 2002; Lephart and Jari, 2002):
- Getting a hand or foot (remember monkeys have hand-like dexterity in both their feet and hands) in proximity to a branch requires hand-eye coordination combining internal representation with stretch proprioception: spindle fibers.
- Initiation of grasping requires recognition of the touch pressure of the new branch in the palm—these receptors are part of your somatosensory system.
- Grasping requires activation of hand-finger muscles via UMNs, and the needed force of the grasp must be calculated via with the monkey's knowledge of the grip necessary to hold its body weight—Golgi tendon organs in the hand/fingers and somatosensory touch receptors in the skin of the hand/fingers.
- Once grip is established, this perception needs to be coordinated with release of the previous branch, via interaction between ascending proprioception and touch from Golgi tendon organs and somatosensory touch receptors; also, via ascending sensory systems providing conscious realization, which feeds back through various UMN systems to the hand and fingers of the previous limb for release or diminishment of force from the grip.
Ideally, these stunningly coordinated events are automated into a motor program habit to allow them to occur in smooth progression. The monkey can attend to the bigger picture towards good (food, conspecifics) and away from bad (predators, angry alpha males). Such a trajectory requires integration of subtle shoulder motions in the swing with visual appreciation of branch options along with following the optic flow to gauge speed. This is a remarkable demonstration of systems coordination!