SPINAL CORD CIRCUITS AND MOTOR CONTROL

Transcription

1 OVERVEW The proximate control of movement is provided by neurons in the spinal cord and brainstem. The primary motor neurons located in the ventral horn of the spinal cord gray matter (and the corresponding motor neurons in brainstem motor nuclei) send axons directly to skeletal muscles via the ventral roots and peripheral nerves (or cranial nerves, in the case of the brainstem nuclei). The activity of these lower motor neurons is determined by local circuitry within the spinal cord and brainstem and by descending pathways from the upper motor neurons in the cortex and other brainstem centers, such as the vestibular nucleus and the reticular formation. Circuitry in the spinal cord also mediates a variety of important sensorimotor reflexes. Lower motor neurons, therefore, provide a common pathway for transmitting neural impulses to the skeletal muscles. SPNAL CORD CRCUTS AND MOTOR CONTROL NEURAL STRUCTURES RESPONSBLE FOR MOVEMENT The neuronal assemblies responsible for the control of movement are most easily understood as four distinct but highly interactive subsystems, each of which makes a unique contribution to motor control (Figure 15.1). The first of these subsystems is the circuitry within the gray matter of the spinal cord. The relevant cells include the primary or alpha motor neurons, which send their axons out of the spinal cord to innervate skeletal muscle fibers; and spinal cord interneurons, which are a major source of the synaptic input to motor neurons. All commands for movement, whether reflexive or voluntary, are ultimately conveyed to muscles by the activity of alpha motor neurons (also referred to as lower motor neurons); thus they are, in the words of Charles Sherrington, the final common path for motor behavior. Spinal cord interneurons receive sensory inputs as well as descending projections from higher centers and provide much of the reflexive coordination between muscle groups that is essential for movement. The contribution of this subsystem to motor control is substantial; even after the spinal cord is disconnected from higher motor centers of the brain, appropriate stimulation can elicit highly coordinated motor reflexes. The second motor subsystem consists of neurons whose cell bodies lie in the brainstem and cerebral cortex. The axons of these higher-order or upper motor neurons descend to synapse with interneurons and/or with alpha motor neurons in the spinal cord gray matter. The descending pathways are essential for the control of voluntary movements and are, in a very real sense, the link between thoughts and actions. Descending systems originating in the brainstem are responsible for integrating vestibular, somatic, and visual sensory information to adjust the reflex activity of the spinal cord. Their contributions are critical for basic steering movements of the body, and in the control of posture. Descending projections from cortical areas in the frontal lobe, including Brodmann's area 4 (the primary motor cortex), area 6 (the premo tor cortex), and the supplementary motor cortex 291

2 292 CHAPTER FFTEEN Figure 15.1 Overallorganizationof neural structures involvedin the controlof movement.four distinct systems-spinal cord circuits,descendingsystems,the basal ganglia,and the cerebellum-make essentialand distinct contributionsto motor control. DESCENDNG SYSTEMS Upper Motor Neurons Motor Cortex Planning, initiating and directing voluntary movements BASAL GANGLA Gating proper initiation of movement Brainstem Centers Basic movements and postural control CEREBELLUM Sensory motor coordination SPNAL CORD CRCUTS are essential for planning, initiating, and directing voluntary movements. The influence of these cortical areas is conveyed to spinal cord circuits directly via the corticospinal pathway and indirectly via projections to the brainstem centers, which in turn project to the spinal cord. The third and fourth subsystems are structures (or groups of structures) that have no direct access to alpha motor neurons or spinal cord interneurons; rather, they exert control over movement by regulating the activity of the upper motor neurons that give rise to the descending pathways. One of these subsystems, the cerebellum, is located on the dorsal surface of the pons (see Chapters 1 and 17). ts principal function is to correct errors of movement by comparing the movement commands issued by the cortex and brainstem with sensory feedback about the movements that have actually occurred. Thus, the cerebellum coordinates the components of complex movements. Changes in the output of cerebellar circuits also underlie certain aspects of motor learning. The other subsystem, embedded in the depths of the forebrain, is the basal ganglia (see Chapters 1 and 17). t is more difficult to characterize the contribution of the basal ganglia to motor control, but disorders of basal ganglia function, such as Parkinson's disease and Huntington's disease, attest to their importance in the initiation of voluntary movements (see Chapters 17 and 18). Despite many years of effort, there is still no complete understanding of the sequence of events that leads from thought to movement, and it is fair to say that the picture becomes increasingly blurred the farther one moves from the muscles themselves. t is appropriate then to begin a more detailed account of motor behavior by considering the anatomical and physiological relationships between alpha motor neurons and the muscle fibers they innervate.

3 SPNAL THE TOPOGRAPHY OF MOTOR NEURON-MUSCLE CORD CRCUTS AND MOTOR CONTROL 293 RELATONSHPS The majority of the neurons that innervate the body's skeletal muscles are located in the ventral horn of the spinal cord. Each motor neuron innervates muscle fibers within a single muscle, and all the motor neurons innervating a single muscle (called the motor neuron pool for that muscle) are grouped together into rod-shaped clusters that run parallel to the long axis of the cord for one or more spinal cord segments (Figure 15.2). (A) (B) (C) Medial gastrocnemius injection Soleus injection : o.r- \j, '~~~ -' --'1.: jl., : -(~.. _,,--,--: '~',--,,- _ ~.\ i: : ;r.. _ : 'f , ,. r :L ;'S1 ~ : 'rd,j.,\.. ~ Z.:, r. --,-.\,, ~l,,'----'~----- J--'----'~' _ ),i' ~ Alpha motor neurons Figure 15.2 Organization of motor neurons in the ventral horn of the spinal cord demonstrated by retrograde labeling from individual muscles. Neurons were labeled by placing a retrograde tracer into the medial gastrocnemius or soleus muscle of the cat. (A) Section through the lumbar level of the spinal cord showing the distribution of labeled cell bodies. Alpha motor neurons form two distinct clusters (motor pools) in the ventral horn. Spinal cord cross sections (B) and a reconstruction seen from the dorsal surface (C) illustrate the distribution of motor neurons innervating individual skeletal muscles in the long axis of the cord. The cylindrical shape and distinct distribution of different pools are especially evident in the dorsal view of the reconstructed cord. The dashed lines in (C) represent individual lumbar and sacral spinal cord segments. (After Burke et al., 1977.),:,.,it:,, ',7 J, / \:.. '. \, \

4 294 CHAPTER FFTEEN Figure 15.3 Somatotopic organization of motor neurons in a cross section of the ventral horn at the cervical level of the spinal cord. Alpha motor neurons innervating axial musculature are located medially, and those innervating the distal musculature more laterally. Q ProXim~ ~~ Distal muscles ~ muscles An orderly relationship between the location of motor neuron pools and the muscles they innervate is apparent both along the length of the spinal cord and across the mediolateral dimension of the cord. Thus, the motor neuron pools that innervate the upper extremity are located in the cervical enlargement of the cord, those that innervate the leg in the lumbar enlargement, and so on (see Figure 1.15). The topography of motor neuron pools in the mediolateral dimension can best be appreciated in a cross section through the cervical enlargement (the level illustrated in Figure 15.3). Neurons that innervate the axial musculature (the muscles of the trunk) are located most medially in the cord. Lateral to these cell groups are motor neuron pools innervating muscles located progressively more laterally in the body. Neurons that innervate the muscles of the shoulders (or pelvis), for example, are next, whereas those that innervate the proximal muscles of the arm (or leg) are located more laterally. The motor neuron pools that innervate the distal parts of the extremities lie farthest from the midline. This organizational feature is worth remembering, since it provides a clue about the function of some of the descending pathways described in Chapter 16. Although the following discussion focuses on the motor neurons in the spinal cord, comparable sets of motor neurons responsible for the control of muscles in the head and neck are located in the brainstem. These neurons are in the motor nuclei of the cranial nerves distributed in the medulla, pons, and midbrain. THE MOTOR UNT Most mature skeletal muscle fibers in mammals are innervated by only a single motor neuron; however, individual motor axons branch within muscles to synapse on many different fibers. The muscle fibers innervated by a single motor neuron are distributed over a wide area within a muscle, presumably to insure that the contractile force of the motor unit is spread more evenly (Figure 15.4). n addition, this arrangement reduces the chance that damage to one or a few spinal motor neurons will significantly alter a muscle's action. Because an action potential generated by a motor neuron normally brings all of the muscle fibers it contacts to threshold, a single motor neuron and its associated muscle fibers together constitute the smallest unit that can be activated to produce movement. Sherrington was again the first to recognize this fundamental relationship between a motor neuron and the muscle fibers it innervates, for which he coined the term motor unit. For most muscles, three types of motor units can be identified based on their speed of contraction, the maximum amount of tension they generate,

5 SPNAL CORD CRCUTS AND MOTOR CONTROL 295 (B) - Motor neuron in spinal cord Muscle fibers innervated by a single motor neuron Figure 15.4 The motor unit. (A) Diagram showing a motor neuron in the spinal cord and the course of its axon to the muscle. (B) Each alpha motor neuron synapses with multiple muscle fibers. The motor neuron and the fibers it contacts defines the motor unit. Cross section through the muscle shows the distribution of muscle fibers (red dots) contacted by the motor neuron. and the degree to which they fatigue (Figure 15.5). Fast fatigable (FF) motor units contract and relax rapidly and are capable of generating the largest force. However, as the name suggests, they fatigue after several minutes of repeated stimulation. At the other extreme are slow (5) motor units. These are highly resistant to fatigue (they can maintain a constant force for over an hour of repeated stimulation), but contract more slowly and are capable of generating only a fraction of the force generated by FF units. The third group has properties that are intermediate between the other two. These fast fatigue-resistant (FR) motor units are not quite as fast as FF units but are substantially more resistant to fatigue. An individual FR motor unit generates about twice the force of a slow unit. The differences in the functional properties of the various motor unit types are based largely on differences in the physiological and biochemical characteristics of their constituent muscle fibers. Most muscles contain a mixture of three types of muscle fibers, and all of the muscle fibers belonging to a given motor unit are of the same type. n addition to the type of

6 296 l CHAPTER FFTEEN (A) (B) (C) 100! Fast Fast ~ fatigable <li u >-< fatigable ',,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, 0 u >-<,B '0 30 ~,!100 >< ro Ul 6ro 6 Fast fatigueresistant >-< C), Fast fatigue-resistant <li ~o ~ <li u >-< <li P-. : a Slow Slow VVVVVY'~ 0 a ms 300 a a a 2 ms 4 min 6 60 Figure 15.5 Comparison of the force and fatigability of the three different types of motor units. n each case, the response reflects stimulation of a single motor neuron. (A) Change in tension in response to single motor neuron action potentials. (B) Tension in response to repetitive stimulation of the motor neurons. (C) Response to repeated stimulation at a level that evokes maximum tension. The y axis represents the force generated by each stimulus. Note the strikingly different rates of fatigue. (After Burke et al., 1974.) myosin in the constituent fibers, both the number and the cross-sectional area of a motor unit's muscle fibers determine its contractile properties. For any particular muscle, individual FF units comprise a greater number of muscle fibers than individual S units. Moreover, the muscle fibers associated with FF units are larger in cross-sectional area than those in S units. (FR units are intermediate in these respects.) Thus, compared to an S unit, activation of an FF unit entails the contraction of a greater number of muscle fibers, each of which is capable of generating a greater amount of force. ndividual muscles differ in the proportions of different motor unit types they contain. Muscles involved in postural support, which must supply steady tension for long periods, tend to have a high proportion of slow units. Conversely, muscles that generate extraordinarily rapid movements contain mostly fast motor units (a good example is the extraocular muscles that generate saccades; see Chapter 19). The majority of muscles, however, contain a more even balance of the different motor unit types. The rationale for motor unit diversity within a single muscle lies in how the different types of motor units are recruited to generate force. THE REGULATON OF MUSCLE FORCE ncreasing or decreasing the number of active motor units regulates the amount of force produced by a muscle. n the 1960s,Elwood Henneman and his colleagues at Harvard Medical School found that steady increases in muscle tension could be produced by progressively increasing the activity of the sensory axons that synapsed with the relevant pool of spinal motor neurons. The gradual increase in tension results from the recruitment of motor

7 SPNAL CORD CRCUTS AND MOTOR CONTROL 297 units in a fixed order according to the conduction velocity of the motor axons. Since conduction velocity is a function of axon diameter (which is in turn correlated with cell size), Henneman recognized that the smallest motor neurons in a motor pool must have the lowest threshold for activation, and that they must be the only units activated by weak synaptic stimulation. As the synaptic drive increases, progressively larger motor neurons are recruited. Within the motor pool that innervates a given muscle, S units tend to have small cell bodies and slow conduction velocities and FF units have comparatively large cell bodies and fast conduction velocities. (FR units again have intermediate characteristics.) Thus, as synaptic activity driving a motor neuron pool increases, low threshold S units are recruited first, then FRunits, and finally, at the highest levels of activity, the FF units. Since these original experiments, evidence for the orderly recruitment of motor units has been found in a variety of voluntary and reflexive movements. This relationship has come to be known as the size principle. An illustration of how the size principle operates for the motor units of the medial gastrocnemius muscle in the cat is shown in Figure When the animal is standing quietly, the force measured directly from the muscle tendon is a small fraction (about 5%) of the total force that the muscle can generate. The force is provided by the S motor units, which make up about 25% of the motor units in this muscle. When the cat begins to walk, larger forces are necessary: locomotor activities that range from slow walking to fast running require up to 25% of the muscle's total force capacity. This additional need is met by the recruitment of FR units. Only movements such as galloping and jumping, which are performed infrequently and for short periods, require the full power of the muscle; such demands are met by the recruitment of the FF units. Thus, the size principle provides a simple solution to the problem of grading muscle force. The combination of motor units activated by such orderly recruitment optimally matches the physiological properties of different motor unit types with the range of forces required to perform different motor tasks. The firing rate of motor neurons also contributes to the regulation of muscle tension. The increase in force that occurs with increased firing rate 100 OJ u... 0 ' S 60 ;::l S 'x cos 80 Fast fatigable c: 40 Fast OJ u... fatigue- OJ c, resistant 20 Slow Percent of motor neuron pool recruited Gallop Run Walk Stand Figure 15.6 The recruitmentof motor neurons in the cat medial gastrocnemiusmuscleunder differentbehavioralconditions.slowmotor units providethe tension required for standing. Fast fatigue-resistantunits provide the additional forceneeded for walkingand run- 100 ning. Fast fatigableunits are recruitedfor the most strenuous activities.(afterwalmsleyet al., 1978.)

8 300 CHAPTER FFTEEN depending on the extent of the damage. n addition to paralysis and paresis, the lower motor neuron syndrome includes areflexia (loss of reflexes) and loss of muscle tone (evidenced by a decreased resistance to passive stretch). Reflexes and muscle tone are discussed in more detail in the next section, but it should be obvious that damage to motor neurons prevents, or at least reduces, the transfer of all types of neural activity to muscle fibers, whether voluntary or reflexive. Damage to alpha motor neurons also results in atrophy of the affected muscles, and fibrillations and fasciculations-spontaneous twitches of single denervated muscle fibers or motor units, respectively. The spontaneous contraction of denervated fibers can be recognized in an electromyogram, an especially helpful clinical tool in diagnosing lower motor neuron disorders. THE SPNAL CORD CRCUTRY UNDERLYNG SENSORMOTOR REFLEXES The synaptic circuitry within the spinal cord mediates a number of sensorimotor reflex actions. The simplest of these reflex arcs entails the response to muscle stretch, which provides direct feedback to the motor neurons innervating the muscle that has been stretched (Figure 15.9). The sensory signal for the stretch reflex originates in specialized structures called muscle spindles that are embedded within most muscles (see Chapter 8). Spindles are composed of 8-10 modified muscle fibers called intrafusal fibers arranged in parallel with the ordinary (extrafusal) fibers that make up the bulk of the muscle (Figure 15.9A).Sensory fibers Caafferents, the largest class of myelinated sensory nerve fibers) are coiled around the central part of the spindle. Stretching the muscle deforms the intrafusal muscle fibers, which leads to increased activity of the sensory fibers that innervate each spindle. The sensory fibers synapse directly on the alpha motor neurons in the ventral horn of the spinal cord (as well as transmitting sensory information to higher centers; see Chapter 8). Thus, activation of muscle spindles produces a rapid increase in muscle tension that opposes the stretch (Figure 15.9B). Borrowing a concept from engineering, the stretch reflex arc can be viewed as a negative feedback loop that tends to maintain muscle length at a constant value (Figure 15.9C).The desired muscle length is specified by the activity of descending pathways that influence the motor neuron pool. Deviations from the desired length are detected by the muscle spindles; thus, increases or decreases in the stretch of the intrafusal fibers change the level of activity in the sensory fibers that innervate the spindles. These changes, in turn, lead to appropriate adjustments in the activity of the alpha motor neurons, returning the muscle to the desired length. One of the most important determinants of any feedback system is its ability to adjust the regulated variable, a property called gain. The larger the gain of the stretch reflex, the greater the change in muscle force that results Figure 15.9 Stretch reflex circuitry. (A) Diagram of muscle spindle, the sensory ~ receptor that initiates the stretch reflex. (B) Stretching a muscle spindle leads to increased activity in a afferents and an increase in the activity of alpha motor neurons that innervate the same muscle. a afferents also excite the motor neurons that innervate synergists and inhibit the motor neurons that innervate antagonists. (C) The stretch reflex operates as a negative feedback loop to regulate muscle length.

9 SPNAL CORD CRCUTS AND MOTOR CONTROL. 301 (A) Muscle spindle (B) (C) Descending facilitation and inhibition ex Motor neuron Force required to hold glass Disturbance (addition of liquid to glass) Length change in muscle fiber ncrease spindle afferen t discharge Spindle receptor

10 302 CHAPTER FFTEEN from a given amount of stretch applied to the intrafusal fibers.f the gainof the reflex is high, then a small amount of stretch applied to the intrafusal fibers will produce a large increase in the number of alpha motor neurons recruited and a large increase in their firing rates; this, in turn, leads to a large increase in the amount of tension produced by the extrafusal fibers.t the gain is low, a greater stretch is required to generate the same amount 0\ tension in the extrafusal muscle fibers. n fact, the gain of the stretch reflexis continuously adjusted to meet different functional requirements. For example, when standing in a moving bus, the gain of the stretch reflex can be increased to compensate for the large disturbances that ensue when the bus stops or starts abruptly. The need to adjust the gain ofthe stretch reflex explains why the spindle sensors are themselves modified muscle fibers. The gain is adjusted by changing the level of activation of a distinct class of motor neurons that innervate the spindle (intrafusal) fibers. These small gamma motor neurons are interspersed among the alpha motor neurons in the ventral horn of the spinal cord. An increase in the activity of gamma motor neurons produces an increase in the amount of tension in the intrafusal fibers. Although the intrafusal fibers are much too sparse to generate a net increase in muscle tension, contraction of the intrafusal fibers increases the sensitivity of a sensory fibers to muscle stretch. The same stretch can then produce a larger amount of a afferent activity, which causes an increase in the activity of the alpha motor neurons that innervate the extrafusal muscle fibers. The activation of gamma motor neurons and the subsequent shortening of intrafusal muscle fibers can also ensure that spindle afferents continue to transmit information when a muscle shortens following contraction. During voluntary movements, alpha and gamma motor neurons are often coactivated by higher centers to prevent muscle spindles from being unloaded (Figure 15.10). n addition, the level of gamma motor neuron activity can be modulated independently of alpha activity, in a contextdependent fashion. n general, the baseline activity level of gamma motor neurons increases with the speed and difficulty of the movement. For example, experiments on cat hindlimb muscles show that gamma activity is high when the animal has to perform a difficult movement, such as walking across a narrow beam. Unpredictable conditions, as when the animal is picked up or handled, also lead to marked increases in gamma activity and greatly increased spindle responsiveness. Gamma motor neuron activity, however, is not the only factor setting the gain of the stretch reflex. The gain also depends on the level of excitability of the alpha motor neurons that serve as the effector side of this reflex loop. Thus, other local circuits in the spinal cord, as well as descending projections, can influence the gain of the stretch reflex via excitation or inhibition of either alpha or gamma motor neurons (Box B). The action of the stretch reflex is not limited to the muscle that has been stretched. Spindle afferents also make direct (although fewer) connections to motor neurons innervating muscles that have similar actions (called synergists) and to intemeurons in the gray matter of the spinal cord (referred to as a inhibitory intemeurons) that synapse on motor neurons innervating antagonist muscles. Thus, increasing the stretch on a particular muscle leads to a coordinated contraction of the synergists and relaxation of the antagonists that move the same joint. This arrangement, whereby the activity of a muscle spindle excites its own muscle and its synergists while inhibiting the action of its antagonists, is an example of reciprocal innervation. Reciprocal innervation is of value in controlling voluntary movements

11 306 CHAPTER FFTEEN Figure Negative feedback regulation of muscle tension by Golgi tendon organs. b afferents from tendon organs contact inhibitory interneurons that decrease the activity of alpha motor neurons innervating the same muscle. b inhibitory interneurons also receive input from other sensory fibers, as well as from descending pathways. This arrangement prevents muscles from generating excessive tension. Descending pathways neuron Flexor muscle cutaneous afferent fiber from nociceptor (Ao) / FLEXON REFLEX PATHWAYS neuron Cutaneous receptor Figure Spinal cord circuitry responsible for the flexion reflex. Stimulation of cutaneous receptors in the foot leads to activation of spinal cord circuits that withdraw (flex) the stimulated extremity and extend the other extremity to provide compensatory support. So far, the discussion has focused on reflexes whose sensory receptors are located within muscles or tendons. Other reflex circuitry, however, mediates the withdrawal of a limb from a sudden painful stimulus, such as a pinprick or the heat of a flame. Contrary to what might be imagined, given the speed with which we are able to withdraw from such stimuli, this flexion reflex involves several synaptic links (Figure 15.13). As a result of this circuitry, stimulation of nociceptive sensory fibers leads to excitation of ipsilateral flexor muscles and inhibition of ipsilateral extensor muscles. Flexion of the stimulated limb is accompanied by an opposite reaction in the contralateral limb; extensor muscles are excited while flexor muscles are inhibited. This crossed extension reflex serves to enhance postural support during withdrawal from the painful stimulus. Like the other reflex pathways, interneurons in the flexion reflex pathway receive converging inputs from several different sources, including cutaneous receptors, other spinal cord interneurons, and descending pathways. Although the functional significance of this complex pattern of connectivity is uncertain, changes in the character of the reflex following damage to descending pathways provide a clue. Under normal conditions, a noxious stimulus is required to evoke the flexion reflex; following damage to descending pathways, however, other types of stimulation, such as moderate squeezing of a limb, can produce the same response. Thus, the descending projections to the cord may function, at least in part, to gate the responsiveness of interneurons in the flexion reflex pathway to a variety of other sensory inputs.