Neurophysiology of locomotor automatism.

Physiological Reviews PubLished and Copyright by The American PhysioLogical Society

Neurophysiology M. L. SHIK Institute

Vol. 56, No. 3, July 1976

of Locomotor AND

Automatism

G. N. ORLOVSKY

of Information Transmission Problems, Academy and Moscow State University, Moscow, USSR

I. II. III. IV.

of Sciences,

Introduction .......................................................... Limb Movements and Muscle Activity .................................. Multilevel Control System ............................................. Automatic Control System ............................................ A. Two automatisms .................................................. B. Two types of supraspinal control systems ............................ C. Common features of systems controlling locomotion in different animals. ........................................ V. Subthalamic Locomotor Region ...................................... VI. Mesencephalic Locomotor Region VII. Monoaminergic Neurons of Lower Brainstem ........................... VIII. Reticulospinal, Vestibulospinal, and Rubrospinal Neurons ............... IX. Cerebellum ........................................................... X. Spinal Cord .......................................................... XI. Interlimb Coordination ................................................ XII. Hypotheses on Organization of Spinal Automatism of Stepping .......... A. Chain-reflex hypothesis ............................................ B. Reciprocal half-center hypothesis ................................... C. Ring hypothesis ................................................... XIII. Conclusion ............................................................

I.

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INTRODUCTION

In this review we apply the term Locomotion to the movement of terrestrial animals on a firm flat surface along a direct line, maintaining equilibrium and using the whole range of normal velocities and gaits. According to this definition, animals with brain structures partially destroyed or removed can also walk. However, such animals may lose the ability to initiate locomotion or to get around obstacles that they encounter during locomotion, and they appear to move aimlessly. In some of these animals, locomotion cannot be evoked by exteroceptive input but only by electrical stimulation of a certain region of the brainstem. Locomotor movements of such “invalid” 465

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animals may differ slightly from those of normal ones. However, we do not use the term Locomotion in cases where the basic pattern of the limb stepping movements is disturbed, the animal cannot use all the natural gaits, or the animal is not capable of keeping equilibrium even though it can perform stepping movements. The data included in this review have been obtained mainly in experiments on cats, to a smaller extent on dogs, and in only a few cases on animals of other species. The main problems discussed are as follows: 1) the automatic system controlling locomotion; 2) the role of supraspinal centers in the control of locomotion; and 3) the possible arrangement of the spinal automatism of stepping. To obtain a clearer picture of some other aspects of locomotion one may also refer to recent monographs (50, 60, 174, 176), a recent review by Grillner (67), and another review (132) that discusses mainly the activity of single neurons during locomotion. II.

LIMB

MOVEMENTS

AND

MUSCLE

ACTIVITY

Before considering the nervous control of locomotion, we shall briefly describe the main features of limb movement and muscle activity during stepping. It is convenient to divide the cycle of stepping into the stance and swing phases. During the stance phase, the limb is in contact with the ground and moves backward in relation to the body. During the swing phase, the limb is elevated and protracted forward. At slow and moderate speeds of locomotion, dogs and cats use a diagonal type of gait, in which there is continuous transition from the walk to the trot. At slow walk, a phase with four limbs on the ground alternates with that of three limbs on the ground. At high-speed trot, phases when two diagonal limbs are on the ground alternate with phases when all four limbs are lifted. For example, when a dog is walking on the treadmill with a speed of 2 km/h, duration of the stance phase is almost 3 times greater than that of the swing phase, and the phase shift between movements of the diagonal foreand hindlimbs is almost a quarter of the cycle. The greater the speed of locomotion, the shorter the stance phase and the smaller the phase shift between movements of the diagonal limbs. At a speed of 8 km/h the swing phase is only 20% shorter than at 2 km/h, whereas the stance phase is 3 times shorter; in addition, at 8 km/h the diagonal limbs move in phase (10). In a diagonal gait, the limbs of one girdle step in alternation -i.e., with a phase shift equal to half of the cycle, independent of the speed of locomotion. At a gallop, however, limbs of one girdle (in the cat only of the hindlimb) move in phase or nearly in phase. The animal can change gait from trot to gallop, and vice versa, abruptly during one step. In the first part of the swing phase all three main joints of the limb (for the hindlimb, the hip, knee, and ankle) are flexing. In the last part of the swing phase the knee and ankle extend, while hip flexion continues to the end of the swing phase. In the stance phase the hip finally extends (10, 36, 57,


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139). At the beginning of the stance phase, the knee and ankle flex to some extent, which is considered to be a result of a passive “yield” (64), and after the yield they are extending until the end of the stance phase. The above sequence of joint movements is fixed and does not depend on the speed of locomotion (lo), but other parameters of the step (duration of its parts, amplitudes of the joint movements) can vary. Thus we consider the sequence as the characteristic feature of locomotion-the basic pattern of the Limb stepping movement. In other kinds of movement, sequences of flexions and extensions in the various joints can be quite different. Therefore, it seems likely that special “connections” are established between different joints of the limb during locomotion. Muscle activity during locomotion is usually studied by means of electromyography. This method, however, gives no information concerning the (negative) work of inactive muscle while it is loaded, and there is also a time lag between the electromyogram (EMG) and mechanical output. Stepping movements of the cat hindlimb have been studied better than those of the forelimb. The hindlimb appears to be more specialized in stepping. Besides, in studying the spinal mechanisms of stepping, preparations with spinal cord transected at a low thoracic level are considerably more convenient and reliable compared with those transected at a cervical level. Naturally, in the former only the automatic mechanisms of hindlimb stepping can be studied. Most of the limb muscles are active in the stance phase. Some begin activity in the last part of the swing phase and are partly responsible for knee and ankle extension, although this extension seems to be produced mainly by inertia and reactive forces (67). Other muscles become active a little later, just before the foot is landed (36). Muscles of a second (smaller) functional group become active at the end of the stance phase and in the beginning of the swing phase and are responsible for flexion and protraction of the limb. The first group of muscles is usually designated as extensor, although it includes adductors and some others. The second group of muscles is designated as flexor, in spite of the fact that rotators and muscles having other functions are also included. Some two-joint muscles are either active in step phases that do not coincide with those of the main groups or they become active twice per cycle (36, 51). After deafferentation of the limb, such muscles can exhibit either one or two bursts per cycle (67, 135). However, in UrodeZa the pattern of activity of forelimb muscles during locomotion does not change after deafferentation of these limbs (179). Thus, there are two maxima of limb muscle activity during the step cycle: one at the beginning and in the middle of the stance phase (when extensors are active) and another at the beginning of the swing phase (when flexors are active). In normal locomotion, however, overall muscle activity does not fall to zero anywhere, i.e., there is no phase within the step cycle in which no motor units are active (51). The duration of the stance phase and associated extensor muscle activity varies inversely with the speed of locomotion. In contrast, the duration of the


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swing phase and that of the flexor activity scarcely changes with speed. The sequence of the beginnings and terminations of activity of most muscles of a limb within the cycle in diagonal gait also does not depend on the speed. Only in gallop does the pattern of activity in some two-joint muscles change (36, 51). Thus, the sequence of activity in different muscles (of one limb) varies somewhat more than does the basic pattern of joint movements. The smaller variability of the kinematic pattern may be explained by the fact that the same mechanical result can be obtained by various combinations of muscle activities. There are two possible ways to control the speed of locomotion: by varying the propulsive forces developed by limb muscles or by varying the frequency of stepping. Experiments in which a dog ran on the treadmill band moving either horizontally or uphill suggest that the animal controls primarily the muscle forces but not the frequency of stepping (131). The amplitudes of joint movements increased with any hampering of locomotion: e.g., increasing the treadmill speed, tilting the treadmill band uphill, or pulling the dog backward. On the other hand, the frequency of stepping increased significantly only with the increase of the speed of locomotion. The frequency of stepping can be increased without an accompanying increase in the amplitudes of joint movements if higher treadmill speed is compensated by decrease of the angle uphill (131). As in other cases, shortening of the cycle is caused mainly by shortening of the stance phase. Thus, the power developed by the animal seems to be a directly controlled parameter. Shortening of the stance phase and, correspondingly, that of the entire step cycle are secondary effects of increased angular velocity of the limb during the stance phase. Probably, increase of speed from 2 to 6 km/h (while run ning on a horizontal surface) is achieved by a small increase of the power developed during the stance phase. Therefore, duration of the swing phase and the amplitude of movements in the hip joint change little (10, 57, 67) . Clear evidence that muscle forces are directly controlled by the brain, whereas the frequency of stepping is controlled only indirectly, was obtained in experiments with mesencephalic cats during controlled locomotion (sect. VI). Increasing the strength of midbrain stimulation producing locomotion resulted in increasing EMG amplitudes in extensors and flexors (151). Consequently, both the power developed by the animal and the amplitudes of the joint movements increased. However, even with stronger stimulation, the duration of the stance phase and the frequency of stepping hardly changed as long as the speed of the treadmill band was kept constant. On the contrary, these parameters of the step cycle could be changed markedly, despite a fixed stimulation strength, by varying the speed of the treadmill band. In this case amplitudes of EMGs did not change significantly (151, 164). The dependence between the stance duration and the speed of locomotion can be described by a model (161) that has some common features with the model of Clark and von Euler (28), proposed for explanation of the dependence between the inspiratory duration and PcoZ in the arterial blood.


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The pattern of limb movement during locomotion is sufficiently constant so that, if external conditions (e.g., the angle uphill) are constant, one can infer the whole pattern of EMGs in the main limb muscles at any speed by using the EMG of only one muscle. Similarly, one can also infer all joint movements knowing only one of them. The stereotyped pattern of limb movement in locomotion indicates that individual muscles and even individual joints are not controlled by the nervous system as elementary units. Rather, the limb is controlled as a whole (188). The basic pattern of the limb stepping movements at different speeds can be obtained (at least to a first approximation) by varying only one parameter. This considerable simplification of the problem of motor control seems to be achieved by the establishment of strong specific interconnections between the nervous centers controlling individual muscles and joints of one limb, which are potentially independent (at least partially) when not used specifically for locomotion. In animals specialized for running, for example the cheetah, the relative mass of two-joint muscles is more than in other animals of the same family (50). In this case, joining up of the limb elements appears to be achieved not only by nervous coordination but also by direct mechanical links between joints. However, this solution may limit the motor versatility of the limb. The idea that motor coordination first of all consists of a reduction in the number of degrees of freedom in the motor apparatus was advanced by Bernstein (15, 16). How this is achieved in locomotion and what are the corresponding nervous mechanisms are central problems in studies of the neurophysiology of locomotion. There is strong linkage not only between joints of one limb but also between the limbs of one girdle, since the phase shift between their movements within one gait is constant and independent of the speed of locomotion. Nevertheless, it seems better to consider an individual limb but not the limb girdle as the functional unit that has its own control mechanisms, since phase shift between symmetric limbs in diagonal gait is not the same as in gallop. Besides, movements of the left and right limbs differ considerably if the animal is turning, circling, or running on a treadmill with the two bands moving at different speeds (9’7). The neurophysiological data suggest also that each limb has its own automatism of stepping (20, 21) -i.e., the limbs can be relatively independent. Interactions between fore- and hindlimbs during locomotion are weaker than between limbs of one girdle. Under certain conditions (e.g., during locomotion on three legs) even the rhythms of the fore- and hindlimb movements can differ (79, 161). Nevertheless, locomotion calls into play linkages that are considerably stronger than those occurring at rest (14, 24, 161). Thus, one may suppose that two main events occur when the animal begins locomotion: 1 > an automatism of steppi ng of each limb is activated and 2) a pattern of interaction between these automatisms is established. These events result in a considerable reduction of the degrees of freedom in the motor apparatus. After the system of locomotor control is activated, regulation of the speed of locomotion is rather simple: the only thing necessary for


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increasing speed is to increase the power developed by the animal. With higher speed of movement, the limbs move faster and reach their caudal extremes more quickly. The stance phase (and duration of the step, correspondingly) becomes shorter and the frequency of stepping increases. It seems likely that arrival of the limb at its caudal extreme can be used by the nervous system not only as a signal for the beginning of the swing phase but also as an input signal controlling interlimb coordination (161). III.

MULTILEVEL

CONTROL

SYSTEM

The motor behavior of the striatal animal and that of intact animals differ considerably, though their purely locomotor movements are nearly the same (145, 194). Even the thalamic cat walks on a flat surface without noticeable defects, but when it meets an obstacle the motor deficiency becomes obvious (35, 99, 110, 146). Striatal and thalamic animals exhibit periodic bursts of motor activity, whereas in subthalamic preparations spontaneous motor activity is weaker. In the latter case, however, locomotion can be evoked by exteroceptive stimulation or by placing the limbs on a moving treadmill band (78, 164). Exteroceptive stimulation can elicit locomotion in chronic mesencephalic cats (12, 192, 199) and dogs (94). Chronic mesencephalic kittens (17) and rats (199) are even capable of spontaneous walking. However, the acute mesencephalic cat (either adult or 2 wk old) cannot walk either spontaneously or with nociceptive stimulation (78), but electric stimulation of a region of the midbrain can evoke locomotion (sect. VI). Thus, the midbrain and lower parts of the central nervous system are sufficient to generate patterns of locomotor movements but more rostra1 structures are necessary for initiation of locomotor behavior and spatial orientation. The isolated spinal cord ordinarily does not generate locomotion in the dog and cat. However, stepping movements of the hindlimbs can be observed after section of the spinal cord at the low thoracic level. In chronic experiments (not earlier than several days after surgery), stepping movements of hindlimbs appear in the dog suspended so that its hindlimbs are passively extended (48). Such movements seem to arise as a result of hip extension under the force of gravity acting on the hindlimbs. A similar phenomenon (i.e., walking on hindlimbs) occurs in chronic spinal pigeons and rabbits and in cats in which the forequarters are fixed on a carriage that is pulled forward (183, 184). Duration of the step cycle depends on the speed of the carriage. Kittens with the spinal cord sectioned several days after birth that are stimulated and trained in a special way can walk on all four limbs (169). If the lumbosacral division of the spinal cord is isolated in an 8- to 14.day-old kitten, the animal can, in some months, walk on the hindlimbs on the moving treadmill band even when the forelimbs are fixed. The duration of the cycle is dependent on the band speed and the hindlimbs support the hindquarters (65). Thus, the basic pattern of the stepping movement can be generated by the spinal cord isolated from the brain. In this case, an afferent inflow from


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the hindlimbs is sufficient for regulation of both the cycle duration and extensor activity in accordance with the speed of locomotion and weight of the body. IV.

AUTOMATIC

CONTROL

SYSTEM

A. Two Automatisms Control of locomotion by the brain centers is simplified thanks to what is called the spinal automatism of the step cycle. As noted above, phases of activity of individual muscles within the cycle are determined by the spinal automatism and the brain appears to influence directly only the overall level of muscle activity (121, 151). The brain can regulate the speed of locomotion by controlling muscle force (see above) but only indirectly (by means of the feedback included in the spinal automatism) affects the duration of the stance phase and, correspondingly, the frequency of stepping. Signals from the brain to the spinal cord for power regulation may well be phase independent (i.e., tonic) and identical for various limbs. Besides generation of steppin, 0 movements and regulation of power, there is another task in the control of locomotion: interlimb coordination and maintenance of equilibrium. This task seems to be solved by a second, larger automatic system, including not only the spinal cord but also some brainstem structures. Unfortunately, data concerning this system are scarce. One may suppose that, like the spinal automatisms of stepping, this second automatism is activated and regulated in part by a certain tonic inflow. However, there is probably a cyclic process in this automatism as well since cyclic signals are necessary both for interlimb coordination and for maintaining equilibrium in the mechanical system moving cyclically. The spinal automatism of the stepping limb includes both a central program and reflex (proprioceptive) mechanisms. Similarly, the brainstemspinal automatism of equilibrium must include programs of both central locomotor coordination of limbs and of interlimb reflexes (sect. XI). However, in both cases this differentiation is relative since the central program uses afferent signals in its activity. Some observations show that there exists a central program of diagonal coordination of the limbs. Stimulation of a broad region in the brainstem reticular formation results in noncyclic coordinated movement of all four limbs-the tegmental response (78,86,108, 173, 185). The animal in this state looks as if it is “fixed” in a certain phase of the step. Furthermore, in the mesencephalic cat, the type of gait (diagonal or gallop) depends on the strength of midbrain stimulation (sect. VI). Only if the strength is near the threshold for gallop can the gait be changed by varying the speed of the treadmill band (i.e., varying an afferent inflow) (164). As further evidence for the existence of central programming, coordinated locomotor movements of four limbs in the toad can be observed after


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deafferentation of all limbs (61) and even after the transection of all dorsal spinal roots (75). In the curarized spinal rabbit, dihydroxyphenylalanine activity in the (dopa) injection (sect. VII) results in coordinated alternating nerves to homonymous muscles of symmetric hindlimbs, whereas the bursts in these nerves are in phase during periods of spontaneous activity in curarized rabbits that are precollicularly decerebrated (190). Brown (19) showed that section of the spinal cord in the cat was followed by a short period of alternating activity of the flexor and extensor muscles in the deafferented hindlimb, homonymous muscles of symmetric hindlimbs being active alternately. Similar results have been obtained by recording activity of the muscle nerves in the curarized cat (134). One may conclude that: 1) some features of the step are controlled mainly by the spinal automatism of the stepping limb, whereas others are also subjected to influences from other limbs and from the brain; 2) a cyclic process in the automatism of equilibrium and a corresponding distribution of the signals to various muscles are probably determined to a large extent by the cerebellum (34). B. Two Types of Supraspinal

Control Systems

The control of the above two-level automatism seems to be relatively simple (160). It is sufficient to define the degree of activation of the automatisms of stepping limbs and the type of interlimb coordination-for example, the diagonal one. At rest, both automatisms are inactive, and the spinal one seems even to be tonically inhibited (sect. x). Therefore, to initiate locomotion both automatisms must be activated. The two-level locomotor automatism can be controlled by a center with a relatively simple intrinsic structure. This suggestion makes concrete Tsetlin’s idea (187) of a rational organization for control systems. The proposed center may receive nonspecific inflow and generate corresponding tonic output signals. Activity of this center would then determine the intensity of locomotion. Two brain centers could serve as inputs to the automatic system of locomotor control: the locomotor region of the subthalamus (sect. v) and the midbrain locomotor region (sect. VI). Apparently, these centers send their signals to the locomotor automatism (Fig. 1) through monoamine& (with unmyelinated axons) and reticulospinal (with thin myelinated axons) neurons of the lower brainstem (31, 32, 37-40). These neurons may be under corticofugal control (163). Besides the system that activates the locomotor mechanisms and controls intensity of locomotion, there is another supraspinal system, including some structures of the brainstem and cerebellum, participating in the control of equilibrium during locomotion. This system differs considerably from the first in that its input and output are somatotopically organized. Apparently, it sends signals to the spinal cord through reticula-, vestibulo-, and rubrospinal neurons with fast-conducting axons. Seemingly, the targets of these influences are motoneurons as well as interneurons mediating spinal reflexes


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RETICULOSPINAL NEURONS WITH SLOW-CONDUCTING AXONS AND MONAMINERGIC (?) NEURONS

;

MOTONEURONS

l-1 FIG.

1. Scheme

of automatic

control

system

for locomotion.

(68-70, 80, 96, 105, 152, 198) and also, to a small extent, the spinal automatisms of the stepping limbs. This second system influences separately some step parameters in certain phases of the cycle, adapting movements to the supporting surface, maintaining regular interlimb relations, and keeping equilibrium. However, these influences do not disturb the basic pattern of stepping (121). This system can also modify to some extent the locomotor movements, supplying them with specific features according to the current aim of the animal’s overall behavior. This system has to interact with sensorimotor, visual, and some other cortical fields. C.

Common Features of Systems Controlling Locomotion in Different Animals It is natural

to look for common

features

in the systems

controlling


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locomotion among different groups of animals because they have many common features in the structure of their nervous systems even though some swim and others move on the ground or fly. For example, a widespread habit of scratching with a hindlimb crossed over a forelimb is common to most Amniota (102) in spite of great morphological differences between reptiles, birds, and mammals. It is not less natural to suppose that common requirements for systems controlling similar modes of locomotion (for example, terrestrial stepping on limbs) lead to functionally similar control systems but different neurological mechanisms. A first approach is to suggest that the basic neurological process developed during evolution for coordination is the same in related taxonomic group of animals with different modes of locomotion and therefore different coordination tasks. For instance, elasmobranchs have a spinal mechanism generating metachronal activity of sequential somites. The speed of this metachronal wave and the duration of activity in the somite cycle are closely related (66). A basically similar mechanism is possibly responsible for sequential activation of various limb muscles during the stepping cycle in terrestrial vertebrates (sect. XIIC). There are some interesting analogies in the organization of locomotor control systems in animals belonging to very distant taxonomic groups. A tonic discharge in the axons of command neurons of the crayfish (18) and in the descending pathways of thoracic nerve cord of the grasshopper (195) activates the locomotor generators of limbs or wings. In the cat the locomotor automatism can also be activated by a tonic descending discharge (sect. x). Functions of the segmental oscillators in arthropods linked by the connectives (196) correspond in principle to functions of the spinal automatisms of the stepping limbs in mammals, such automatisms all being coordinated by a system of mutual interaction. There are some common features in the distribution of proprioceptive inflow in animals with different neural organization. Such inflow can be addressed directly to motoneurons or to oscillators and command neurons in arthropods and to corresponding neural mechanisms in vertebrates. Apparently the significance of phasic proprioceptive inflow depends on the type of locomotion but not on the taxonomic position of the animal. This phasic inflow appears to be essential if external conditions can vary greatly as in terrestrial locomotion (67), but it can possibly be replaced by a more tonic inflow during locomotion in a homogeneous medium [as in swimming or flight (195>]. It seems likely that few segmental reflexes found at rest can promote stepping movements in vertebrates (36, 104) or in invertebrates (43). The system of proprioceptive and recurrent interaction between motoneurons in the isolated spinal cord tends rather to minimize muscle activity, and one can suppose that this system must be changed considerably during locomotion. It is worth noting that some kinematic parameters of terrestrial locomotion depend on speed in a similar way in multipedes, insects, and man (172). A formal theory of metachronal movements of ipsilateral limbs and of step-


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ping of a single limb (172) is in good agreement with such kinematic data. Evidently, there are some common features in functioning of the nervous locomotor mechanisms of animals belonging to remote taxonomic groups. V.

SUBTHALAMIC

LOCOMOTOR

REGION

Waller (193) discovered that stimulation (60 Hz) of the subthalamic region in the lightly anesthetized cat suspended in a hammock evokes running movements in the limbs. Stimulation of this subthalamic locomotor region (SLR) in the acute thalamic cat evokes locomotion on the treadmill, the cycle duration decreasing at higher speeds of the band (117). With stronger stimulation, muscle activity increases and a diagonal gait can change into a gallop. Hinsey et al. (78) found that the motor behavior of the cat decerebrated at the rostra1 border of the mammillary bodies (subthalamic cat) differs considerably from that decerebrated at the caudal border (me: it tincephalic cat). The subthalamic cat can walk both with exteroceptive stimulation and sometimes spontaneously, but the acute mesencephalic cat does neither. The SLR is located between the levels of these two sections. Bilateral lesion of the SLR eliminates only voluntary locomotion; other types of motor activity are mainly preserved (170; cf. 144). For 7-10 days after destruction of the SLR, a cat does not walk by itself to a plate with food or to a mouse but eats food actively and can even kill and eat a mouse when it can do so without leaving its place. Nociceptive stimulation elicits low hissing, biting, and turning of the head and trunk, but still the animal Joes not leave its place. Such cats walk only when they begin to slip after being put on a flat surface tilted 45-60” downhill; walking stops immediately when the cat reaches the floor (170). Cats with bilateral SLR lesions, although unable to perform voluntary locomotion, nevertheless exhibit coordinated walking and running during stimulation of the midbrain locomotor region (MLR) (sect. VI) (170). Therefore, the automatic control system of locomotion discussed above can work without the SLR. Such cats, when forced to run, never hit the walls of the room and they jump over or go around obstacles. This means that space orientation during locomotion is well maintained without the SLR. Thus, both locomotor coordination and spatial orientation are preserved in an animal that cannot walk voluntarily. It seems likely that the SLR is responsible only for the initiation of locomotion as a part of goal-directed behavior: searching, hunting, defending, and so on. This supposition is in line with the observation that hypothalamic stimulation in intact and even in decorticated animals elicits some afferent-dependent forms of complex motor behavior, similar to natural hunting or flight, etc., but not locomotion itself (46, 143). Thus, the functions of the SLR can hardly be described in purely motor terms. Like other parts of hypothalamus, the SLR seems to take part in the behavioral and emotional life of the animal. It is necessary to note that lo-12 days after the SLR lesion


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the capacity for voluntary locomotion begins to return, and after 3-4 wk the lesioned animal can hardly be distinguished from an intact one (170). A question arises as to why corticofugal influences fail to evoke locomotion after the SLR lesion. The SLR is not necessary for mediating cortifugal influences because, in the acute mesencephalic cat, locomotion can be evoked by stimulation of corticofugal fibers at the pontine level (163). In these experiments both symmetrical pyramidal tracts were transected at the bulbar level and therefore they could not directly influence the spinal cord. It seems doubtful that SLR destruction can change significantly the state of those brainstem neurons that must be activated to evoke locomotion. At least, MLR stimulation can still evoke locomotion after destruction of the SLR. Thus, one can suggest that the SLR lesion primarily affects the state of cerebral cortex. Grossman (73) found that stimulation of nonspecific thalamic nuclei resulted in inhibition of stepping movements elicited by stimulation of the SLR in the lightly anesthetized cat suspended in a hammock. He concluded that this inhibition is specific for locomotion since it affects neither reflex movements nor muscle contractions evoked by stimulation of motor cortex. Furthermore, it was not accompanied by spasticity or atonia. This important conclusion seems to need some additional experimental evidence since the stimulated area was located near the thalamic region producing the “arrest reaction” (84). The thalamic cat exhibits periodic bursts of motor activity with a cycle duration of l-3 min. Stimulation of the SLR always evokes locomotion; stimulation of the MLR is effective only during periods of increased motor activity (117). In chronic experiments on unanesthetized cats with intact brains, stimulation of the MLR evokes locomotion that is accompanied by prominent side effects, which then disappear after lesion of the nonspecific thalamic nuclei or of the SLR (170). Finally, there is a recent report that in the cat with intact brain “stimulation of the posterior region of the thalamus (n. CM) produced backward and forward locomotion or running” (5). VI.

MESENCEPHALIC

LOCOMOTOR

REGION

The mesencephalic locomotor region (MLR) corresponds to the nucleus cuneiformis (Horsley-Clarke coordinates P2, L4, HO) and has a linear dimension of about 1 mm (165). Electrical stimulation (30-60 pulses/s, pulse duration 0.2-0.5 ms) of the MLR evokes locomotion in mesencephalic cats (164) and sometimes in thalamic cats (117) as well as in lightly anesthetized cats with intact brain (170). Usually stimulation of one of the two symmetric MLRs is as effective as simultaneous stimulation of both regions. In acute experiments the head of the mesencephalic cat is usually fixed, but its limbs are lowered on the treadmill band and can perform stepping movements. With MLR stimulation, the acute mesencephalic cat can also walk on the floor without support, but it falls when it meets a wall or any obstacle. During evoked


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locomotion of the mesencephalic cat on the treadmill, arterial pressure is 2035% higher, cardiac output 70-96% larger, and frequency of heartbeat 1520% ventilation increases 3 times on the higher than at rest (171). Pulmonary average as a result of increased tidal volume and frequency of breathing. Thus, hemodynamic changes seem to be of the muscle exercise type but not of the nociceptive type. In chronic experiments, MLR stimulation evokes machinelike locomotion without side effects and with perfect spatial orientation, provided that either the SLR (sect. v) or the ten trum medianu .m-nucleus parafascicu laris complex is destroyed bilaterally (170). In the latter case, no significant defects in the cat’s motor behavior are observed, particularly in spontaneous locomotion. When the MLR is stimulated, cats of both groups cannot remain motionless; i.e., the animal walks or runs continuously while stimulation is maintained. The only thing the cat can do is to avoid collisions with walls or other obstacles. However, in spite of such striking effects of MLR stimulation, after bilateral lesion of the MLR the cat can still walk (170). Destruction of the MLR results in some dyscoordination of hindlimb movements during walking and these cats do not run. Thus the MLR seems not to be necessary either for the initiation of locomotion or for walking in the intact animal. However, behavior of the mesencephalic cat can be changed dramatically by MLR stimulation: before stimulation is started the cat is motionless but during stimulation it walks or runs. It seems likely that, in the intact animal, tonic activity of the neurons of the MLR promotes more powerful locomotion, but at rest these neurons are suppressed by other centers. On the contrary, when released from diencephalic control, the MLR determines the motor activity of the animal. In the mesencephalic cat, lesion of the red nuclei does not change the locomotor effect of MLR stimulation (163); this lesion hardly influences locomotion of intact animal as well (85). Stimulation of the MLR is also effective after removal of the corpora quadrigemina (165). Hence, synaptic excitation of neurons of rubro- and tectospinal tracts is not necessary for the locomotor effects of MLR stimulation. of less than 30 PA. DisplaceLocomotion can be evoked by a stimulus ment of the stimulating electrode by 0.2-0.3 mm leads either to considerable increase of threshold or locomotion cannot be evoked at all. Displacement in the ventromedial direction can result in micturition due to the stimulation of the Barrington point (98). Thus, confusion due to direct stimulation of other midbrain descending pathways in the vicinity of the MLR seems to be excluded in these experiments. Stimulation of MLR does not evoke locomotion if the ventral border of the brain&m transection is done 2-3 mm more caudad than above-i.e., behind (but not rostra1 to, as usual) the exit of the 3rd cranial nerve (165). This small shift hardly would have such a decisive effect if the locomotor effects of MLR stimulation depended on direct excitation of some other axons descending from higher levels to the spinal cord. The latter observation suggests that the


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rostroventral part of the midbrain influences considerably some of the MLR target centers or the MLR itself. Presented data suggest that MLR influences the spinal cord via some structures of the lower brainstem. For example, stimulation of the MLR region (as well as of the more rostra1 midbrain point) can evoke monosynaptic responses in reticulospinal neurons (109, 118). The nucleus cuneiformis (which corresponds to MLR) is connected by a tract with pontine nuclei (92). The rostroventral part of the midbrain, which has a crucial role for locomotion in the mesencephalic cat, becomes unnecessary if the spinal cord is transected at the low thoracic level (25). After this transection, stepping movements of the forelimbs can be evoked by moving the treadmill band. In this case the brainstem can be cut behind the exit of the 3rd cranial nerve. Facilitation of forelimb stepping by section of the spinal cord can be considered a locomotor component of the Schiff-Sherrington phenomenon. One may suppose that either the MLR or the center on which MLR is acting is under two kinds of tonic influence: an inhibitory one from the lumbosacral spinal cord and an excitatory one from the rostroventral part of the midbrain. If the ascending inhibition is abolished, the rostroventral part of the midbrain becomes unnecessary for locomotion. One may suppose that this region facilitates reticulospinal neurons of the lower brainstem. In fact, stimulation of perirubral reticular formation excites reticulospinal neurons (11, 91) whose axons probably belong to the dorsal reticulospinal system (6, 37, 38). One may ask what elements of the MLR are responsible for the locomotor effect of its stimulation: neurons of nucleus cuneiformis or axons passing across this region but originating from cell bodies located elsewhere. Microstimulation (a few microamperes) that excites neurons within a radius of lOO200 pm is sufficient to evoke synaptic (as a rule, monosynaptic) responses in MLR neurons (166). Such units have been recorded extracellularly and identified as cell bodies by their reactions to electrophoretic microapplication of glutamate (200). Thus, there is a sufficient number of excitatory synapses on MLR neurons to excite them synaptically as well as directly when locomotion is evoked by MLR stimulation. Therefore, it is quite possible that the locomotor effect of MLR stimulation is mediated by the neurons of nucleus cuneiformis. However, excitation of the axons passing over the MLR still cannot be excluded. VII.

MONOAMINERGIC

NEURONS

OF

LOWER

BRAINSTEM

There is no direct evidence concerning the motor function of the noradrenergic and serotoninergic neurons located in the brainstem, but the idea of Jankowska et al. (88, 89) and Lundberg (104) that the monoaminergic descending system is able to convert the interneuronal network of the spinal cord into an autonomous system generating stepping has now been supported by a number of indirect findings. Cell bodies of monoaminergic neurons have not been found in the spinal cord, and hence monoaminergic


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terminals in the spinal cord presumably all belong to such neurons with cell bodies in the lower brainstem (26, 31,32). Therefore, effects on the spinal cord exerted by intravenous injection of the precursors in the biosynthetic pathway of norepinephrine and serotonin [3,4-dihydroxyphenylalanine (dopa) and 5hydroxytryptophan (&HTP), respectively] are usually explained as due to release of corresponding mediators from the terminals of these neurons (29, neurons, 39, 40, 44, 189). To imitate activation of descending monoaminergic receptors of spinal neurons (4, 47) Clonidine is used to excite alpha-adrenergic In the spinal cat, dopa and 5-HTP exert strong influence on the spinal neuronal network (39,40,88, 89). For example, the usual short-latency effects of a stimulus applied to the flexor reflex afferents (FRA) -that is, excitation of the flexor motoneurons and inhibition of the extensor ones- disappear. Instead of these effects, a long-latency (X00 ms) and long-lasting (200 or 300 ms) asynchronous activity of flexor motoneurons appears when a short train of stimuli is applied to FRA. During this long-lasting flexor activity, extensor motoneurons are inhibited. Injection of dopa facilitates stepping movements of the hindlimbs in the acute low spinal cat (63). If the hindlimbs are in contact with the moving treadmill band, their stepping is nearly regular and cycle duration decreases with the increase of the band speed (23). If the band reverses direction, the pattern of hindlimb movements inverts: i.e., they step as in an intact animal that wa .lks backward (23). Stepping movements of the hindlimbs can also be evoked after Clonidine injection in low spinal cats (47). In this case the hindlimbs even support the hindquarters and can move not only alternately but also in phase (gallop). In the acute curarized spinal rabbit (i.e., in the absence of cyclic afferent inflow), dopa injection evokes rhythmical reciprocal activity in nerves to antagonistic muscles of the ankle joint (190). However, some days after section of the spinal cord, dopa no longer elicits this cyclic activity (190). In the acute curarized spinal cat, dopa injection does not evoke a rhythmical process but FRA stimulation results in one or sometimes two or three bursts of reciprocal activity in nerves to antagonistic muscles (88). However, bilatera1 stimulation (4-100 Hz) of the L, dorsal roots evokes rhythmic reciprocal activity in these nerves with a period of about 1 s (72). The latter effect can be also obtained after Clonidine injection. One can suggest that MLR stimulation evokes locomotion because of excitation of the noradrenergic descending system. In the mesencephalic curarized cat, such stimulation results in some changes in the state of the spinal cord which are similar to those obtained after dopa injection (71). Furthermore, MLR stimulation does not evoke locomotion after injection of phenoxybenzamine, a blocker of central alpha-adrenergic receptors (65). These observations are compatible with the hypothesis that noradrenergic neurons of the lower brainstem give rise to one of descending pathways through which the brain, and the MLR in particular, activates the spinal automatism of stepping. Injection of 5-HTP evokes the same changes in the state of the spinal cord


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as does administration of dopa, but 5-HTP also increases excitability of motoneurons (3). The effects of MLR stimulation seem closer to those of dopa since the MLR changes the state of the spinal cord even when the strength of stimulation is too weak to change the excitability of motoneurons (71). Nevertheless 5HTP injection also evokes cyclic reciprocal activity in nerves to antagonistic muscles of ankle joint in the spinal curarized rabbit (190). In the intact, lightly anesthetized rabbit, one can observe spontaneous rhythmic activity in these nerves. Both 5-HTP and dopa injection facilitate such activity, 5HTP mainly in flexors and dopa largely in extensors (189). If steppinglike activity is elicited by subcutaneous electric stimulation (sect. x), 5-HTP decreases bursts in the extensor nerve, whereas dopa decreases activity in the flexor nerve (189). All serotoninergic neurons whose axons descend to the spinal cord appear to be located in the raphe nuclei (26, 32). These nuclei seem to be involved in tonic control of FRA interneurons (40). Surgical or pharmacological destruction of the raphe nuclei results in “continuous running movements of forepaws” and insomnia (93, 140). Thus, both subdivisions of the monoaminergic system (i.e., norepinephrine and serotonin) seem to be related to aspects of locomotor control, although evidence concerning the serotoninergic system is less extensive at the moment. Fast-conducting cortico-, rubro-, vestibulo-, and reticulospinal fibers influence mainly motoneurons and interneurons of the reflex arcs. They do not affect those spinal interneurons that seem to be responsible for the generation of stepping. Among myelinated descending fibers, only thin fibers of the dorsal reticulospinal system elicit effects similar to those of dopa or 5-HTP (37, 38, 40). Thus, monoaminergic and dorsal reticulospinal systems seem to be responsible for the activation of locomotor automatism. Unfortunately, there are no reports on selective stimulation of monoaminergic neurons having thin unmyelinated axons. Only recently, recordings of background activity of noradrenergic neurons (of locus coeruleus) (27) and serotoninergic neurons of raphe nuclei (159) were obtained. VIII.

RETICULOSPINAL,

VESTIBULOSPINAL,

AND

RUBROSPINAL

NEURONS

Activity of single neurons of fast-conducting descending pathways has been studied during locomotion of mesencephalic and thalamic cats (119, 120, 122, 123). In these experiments the forelimbs were fixed and only the hindlimbs were stepping on the treadmill band. The neurons with fast-conducting axons reaching the lumbar segments of the spinal cord, i.e., influencing the hindlimbs, were studied. At rest most reticula-, vestibulo-, and rubrospinal neurons have weak background activity, but during locomotion activity of these neurons increases considerably. In most neurons a rhythmic modulation of the activity appears. Usually the discharge frequency of the neuron is high in a particular phase of the step and falls (sometimes to zero) in other phases. The phases of maximal activity differ in different neurons. Most vestibu-


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lospinal neurons are maximally active at the beginning of the stance phase; most rubro- and reticulospinal (from dorsomedial part of the lower brainstem) neurons are maximally active in the swing phase (119, 122, 123). The phasic activity of descending neurons is discussed in relation to the limb that the neurons largely influence, i.e. to the ipsilateral limb in the case of vestibuloand reticulospinal neurons and the contralateral one for rubrospinal neurons. At rest the vestibulospinal tract facilitates extensor motoneurons, the reticulospinal tract mainly facilitates flexor motoneurons and inhibits extensor motoneurons, the rubrospinal and pyramidal tracts mainly facilitate flexor motoneurons (68, 70, 80, 96, 105, 198). Experiments with short-lasting (100-300 ms) electric stimulation of the descending pathways (or of their nuclei of origin) superimposed on locomotion showed that all these pathways exert mainly the same effects on hindlimb motoneurons as they do at rest (121). However, the efficiency of descending influences [as of afferent volleys (162)] depends considerably on the phase of the step. For example, stimulation of Deiters’ nucleus (from which the vestibulospinal tract originates) considerably increases extensor EMGs in the stance phase (when extensors are active) but evokes no response in the swing phase (when they are silent). Corresponding results were obtained for other tracts (121). Thus the phases of maximal activity of the descending pathways mainly coincide with the phases of activity of those muscles on which the same pathways exert excitatory influence. It is in these phases that excitatory descending effects are maximal. However, similarity between the timing of activity in the descending pathways and that in the corresponding limb muscle does not necessarily mean that generation of stepping movements in the mesencephalic and thalamic cats is performed by the brain and not by the spinal cord. It seems more likely that rhythmic modulation of activity of the descending pathways is determined by rhythmic signals coming to the brain from the spinal cord. Indeed, a temporary arrest of one of two stepping hindlimbs results in the cessation of the cyclic modulation of activity of supraspinal neurons whose axons project to this limb (119, 122, 123). Electrical stimulation of the descending pathways, mentioned above, strongly affects the amplitudes of EMGs, either increasing them several times or completely inhibiting them, but this stimulation affects neither the frequency of stepping nor the duration of the stance and swing phases (121). Only very strong stimulation disturbs the rhythm of stepping. Therefore, the fast-conducting descending pathways apparently only modulate stepping movements while the generation of the basic step pattern is performed by the spinal automatism of stepping. Activity of rubro- and reticulospinal neurons has also been studied in decorticated cats, which exhibit periods of spontaneous motor activity. Sometimes locomotion can be evoked by exteroceptive stimulation and, correspondingly, in a curarized animal it is possible to record bursts of reciprocal activity in the nerves to antagonistic muscles (134). During the period of rhythmic activity in the curarized decorticate cat, the discharge rate of rubro- and reticulospinal neurons increases and a modulation of their discharges ap-


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pears, with a rhythm equal to that of bursts in the muscle nerves (134). Since other evidence (see above) suggests that the rhythm is generated in the spinal cord, this finding indicates that strong ascending influences on the rubro- and reticulospinal neurons exist even when cyclic inflow from the limb receptors is absent. In these experiments, bursts of activity in the nerve to tibialis anterior muscle coincide with minimal activity of most rhythmically modulated contralateral rubrospinal neurons (l34), and thus activity of rubrospinal neurons could not be responsible for the cyclic excitation of flexor motoneurons. Phases of maximal activity of various reticulospinal neurons were related in different ways to the phase of bursts in the nerve to the tibialis anterior muscle. Recording of activity of axons ascending in the lateral funiculus of the spinal cord shows that this activity is also modulated with the rhythm found in the muscle nerves (134). Thus even in the paralyzed decorticate cat without phasic afferent inflow, the cyclic ascending and descending activity circulates between the spinal cord and supraspinal centers during periods of spontaneous motor activity. Cyclic activity in a filament from ventral root L, can be observed during stimulation of the MLR in the curarized premammillar cat (162) and in the decerebrate cat with de-efferented hindlimbs (126). However, in the curarized postmammillar cat (which before curarization is unable to walk either spontaneously or with exteroceptive stimulation) cyclic activity cannot be evoked by MLR stimulation. However, a cyclic activity of motoneurons does appear if limbs are cyclically moved by hand during MLR stimulation (162). It seems likely that integrity of the diencephalon and prosencephalon enhances the role of supraspinal cyclic processes in the control of locomotion. Observed differences in the motor activities of the thalamic (or premammillar) and mesencephalic preparations (sect. v) may be related to differences in the background activity of reticulospinal neurons, which in the mesencephalic cat is significantly lower (120). In chronic experiments on cats, it has been shown that after incomplete section of the spinal cord at the upper lumbar level (leaving only the ventral funiculi intact) the hindlimbs still take part in locomotion, but their movements are not in phase with movements of the forelimbs (2). Probably, after this section, the descending fibers that transmit signals activating the spinal automatism of the hindlimbs stepping are preserved, but the pathways responsible for the forelimb-hindlimb coordination are interrupted. However, in the monkey, participation of the hindlimbs in locomotion has been described even after ventral hemisection of spinal cord at a low thoracic level (56). The apparent contradiction between these data might result not from a different course of classic descending pathways in the cat versus monkey, but because in each case different numbers of monoaminergic axons or axons of the dorsal reticulospinal system (3’7) might remain intact. It is also possible that in the monkey corticospinal control of locomotion is more significant. IX.

CEREBELLUM

Disturbances

of locomotion

after either lesions or ablation

of the cerebel-


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lum have been described many times (34). These disturbances are especially prominent if the cerebellar ablation is accompanied by lesion of the sensorimotor or frontal cortex or by hemispherectomy. The chronic striate cat without a cerebellum cannot walk (49); in the acute thalamic cat without cerebellum (the head being fixed), locomotion can be elicited by stimulation of the SLR or sometimes the MLR (120). In the mesencephalic kitten (6-11 days old) suspended in a hammock, stepping movements can be evoked by MLR stimulation, even though at this age the cerebellar structures are not yet developed (147). Limb movements during evoked locomotion are poorly coordinated in thalamic and especially in mesencephalic animals without a cerebellum. Various effects of acute cerebellectomy may be responsible for the dyscoordination: e.g., operative shock, or decreased activity of y-motoneurons and corresponding decreased and inadequate inflow from the spindle afferents (X5), or abnormal muscle tonus [a-rigidity (58)], or an abnormal state of various spinal and brainstem reflexes. In addition, the absence of a specific cerebellar function (e.g., processing of cyclic ascending inflow) may also be significant. After cerebellectomy, background activity of vestibulospinal neurons increases (129) and cyclic modul ation of the discharge of neurons of the lateral reticular nucleus persists when limbs perform stepping movements (9) . These observations suggest that operative shock is not the main reason for dyscoordination. Activity in rubro- and reticulospinal neurons does decrease, however, probably due to absence of tonic facilitation from the cerebellar nuclei. The changes of “average” activity in the descending pathways may result in abnormal relations between flexor and extensor tonus. Besides these changes, modulation of the discharge in reticula-, vestibulo-, and rubrospinal neurons with the rhythm of stepping almost disappears (120, 122, 123). Probably, these two effects are the main reasons for locomotor ataxia after removal of the cerebellum in acute mesencephalic and thalamic cats. Response of reticula-, vestibulo-, and rubrospinal neurons to adequate vestibular stimulation (tilting in the frontal plane) also changes considerably after cerebellar ablation: a dynamic component of response is replaced by a static one (129). During evoked locomotion of preparations with or without cerebellum, vestibular reflexes in these neurons are diminished (128, 130), an effect that can hardly be explained by occlusion of vestibular and other sources of activation of these neurons during locomotion. Rhythmic modulation of fast-conducting descending pathways during locomotion of mesencephalic and thalamic cats is determined to a large extent by the cerebellum. Correspondingly, activity of Purkinje cells in the cerebellar projection zone of the hindlimb and activity of neurons of the fastigial and interpositus nuclei are both modulated in the rhythm of stepping (124, 125). The sources of this cyclic modulation, as in the case of neurons of the three classic descending pathways, are ascending influences from the spinal cord, since temporary arrest of the stepping limb results in cessation of cyclic modulation.


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Neurons of the dorsal spinocerebellar tract (DSCT), during locomotion in the mesencephalic cat, send messages reflecting peripheral motor effects, i.e., degree of activation and extension of muscles, touching of the foot down, etc. (7, 9). After d ea ff erentation of the hindlimbs, cyclic modulation of activity of DSCT neurons disappears. However, neurons of the ventral spinocerebellar tract (VSCT) depend less directly on localized sources of afferent activation and their receptive fields are extremely broad (133). During locomotion, VSCT neurons are active in certain phases of the step, but in various neurons those phases can be different. The VSCT neurons continue their cyclic activity during evoked locomotion even after deafferentation of the hindlimbs (8, 9). Thus VSCT neurons send messages not only about peripheral processes but also about activity in the spinal network (103, 106, 133). It seems likely that neurons of the VSCT are cyclically modulated largely by lumbar interneurons involved in generation of stepping. Additional possible sources are afferent inflow from hindlimb receptors and from those of the forelimbs (via propriospinal connections or mediated by the brain), plus cyclic activity of motoneurons mediated by Renshaw cells and inhibitory la interneurons (sect. xrB). Neurons of the lateral reticular nucleus (the second-order neurons in the spinoreticulocerebellar pathway) are also cyclically active during locomotion (9). Therefo re, spinoreticular neurons must be cyclically active too. There are no data concerning activity of the spino-olivocerebellar tracts during locomotion, but the cyclic activity of other spinocerebellar pathways (i.e., those ending as mossy fibers) presents a reliable basis for cyclic activity of the cerebellar neurons. In turn, cerebellar output neurons present an important source of rhythmical modulation of the reticula-, vestibulo-, and rubrospinal neurons (119, 120, 122, 123). However, in the acute decorticated cat, cyclic modulation of activity in rubro- and reticulospinal neurons can be observed (during periods of spontaneous locomotion) even after removal of the cerebellum (134). X.

SPINAL

CORD

In this section, the activity of cy- and y-motoneurons during evoked locomotion of the mesencephalic cat is considered as well as the capacity for stepping peculiar to the spinal preparation. It was noted (sect. II) that duration of the stance phase varies considerably according to the speed of locomotion and the same is true for activity of extensor muscles. On the contrary, the duration of the swing phase and associated flexor activity hardly depend on the speed of locomotion (151). More intensive locomotion (i.e., increased muscle activity) is achieved by recruiting new ar-motoneurons but not by increasing their individual discharge rates. In most cr-motoneurons, interspike intervals range from 25 to 40 ms (151). In an individual motoneuron, the mean interspike interval within a burst is nearly constant in successive steps and at any speed and intensity of


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locomotion (except for transitory periods at the beginning and end of locomotion, in which interspike intervals are longer). An individual cu-motoneuron is either inactive (when intensity of locomotion is weak) or active with a mean interspike interval standard for this neuron. Various motoneurons become active at different intensities of locomotion. When active, an a-motoneuron generates bursts in each step at the same phase of the cycle (151). The discharge rate of cu-motoneurons during locomotion is so high that the motor units must work in a near-tetanic mode. However, in postural activity the average discharge rate is considerably lower and change of firing frequency would result in a significant change of motor unit force. The “fixed” mode of the activity of a-motoneuron during locomotion is quite different from activity during voluntary movement, when rather broad variations of discharge frequency are possible (115, 138). This difference probably reflects the difference between the usage of a-motoneuron by the automatic program of stepping and by the presumably different control mechanism in voluntary movement. Activity of y-motoneurons during evoked locomotion differs considerably from that of cu-motoneurons. Severin et al. (148, 149) showed that discharge frequencies of y-motoneurons strongly depend on the strength of MLR stimulation (i.e., on the intensity of locomotion). The “depth” of cyclic modulation (in the rhythm of stepping) also depends on the strength of MLR stimulation: with stronger stimulation y-motoneurons discharge in one part of the cycle and become silent in other parts (148, 149). -Study of activity of spindle afferents during locomotion leads one to conclude that fusimotor motoneurons are maximally active in phase with homonymous ar-motoneurons. Similar cyy-coactivation has already been found in motoneurons of the intercostal muscles during respiration (30). Deafferented hindlimbs of the mesencephalic cat [and of animals with intact central nervous system (181>] participate in locomotion when the forelimbs walk (162). Therefore signals from proprioceptors in the limb are not necessary for activation of a-motoneurons, and the role of the y-loop is evidently not to initiate muscle contraction but to increase (corresponding to intensity of locomotion) the sensitivity of muscle spindles in certain phases of the step (58, 111). In particular, modulation of the activity of the y-motoneurons displaces la facilitation of homonymous cu-motoneurons from that part of the cycle when the muscle is extended passively to that part when it contracts actively. Coactivation of homonymous CY-and y-motoneurons of the deafferented hindlimb has also been found in the decorticated cat during periods of spontaneous motor activity (137). In some cycles (usually at the beginning and end of the period of motor activity), rhythmic modulation of the spindle afferents (reflecting activity of y-motoneurons) was observed without any activity of homonymous cu-motoneurons. Activation of static y-motoneurons prevails in flexors; that of dynamic ones dominates in extensors (136, 137). In acute spinal mammals it is not simple to evoke stable stepping. In a cat suspended in a hammock, unstable stepping movements of the hindlimbs


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continue 20-30 s after section of the spinal cord (19, 134). Sometimes they can be evoked also by nociceptive stimulation of the perineal region (1, 116). Section of the spinal cord can also evoke a burst of stepping movements after deafferentation of the hindlimbs (19). More stable stepping movements of the ipsilateral hindlimb in the air can be evoked in the decapitated cat by stimulation (30-100 pulses/s) of the dorsolateral part of the cut spinal cord at the C, level (141, 155, 158). In the precollicular cat with de-efferented hindlimbs, MLR stimulation can evoke cyclic activity in a filament from ventral root L, (126). The effect depends strongly on the tonic afferent inflow; for example, the limb position has a crucial role. In the curarized mesencephalic cat MLR stimulation evokes only noncyclic activation of the hindlimb motoneurons (162), but if the limbs are rhythmically moved by hand the corresponding rhythmic activity appears in the motoneurons. Thus, MLR stimulation apparently produces increased sensitivity of the spinal mechanisms to rhythmical afferent influences in the frequency range of stepping. In the mesencephalic cat, stimulation of the L, or S, dorsal roots with a constant low-frequency current (2-4 pulses/s) can evoke stepping movements of the hindlimbs on a moving treadmill band. The step duration can change from 0.5 to 1.5 s in accordance with the band speed (22). In the mesencephalic curarized rabbit, subcutaneous stimulation with a frequency of 10 pulses/s elicits reciprocal activity in the nerves to antagonistic muscles of the ankle joint with a period of 0.5-1.0 s (29). The same effect is also observed in the curarized rabbit with intact brain under light barbital anesthesia (191). In the chronic spinal kitten (transection at low thoracic level), bilateral stimulation of cut dorsal roots L, (with a frequency between 4 and 100 Hz in different experiments) elicits alternating stepping movements of the deafferented hindlimbs similar to normal diagonal gait (72). The same effect could be evoked by antidromic stimulation of the dorsal columns at the L, level (72), suggesting that the Roaf-Sherrington effect (141, 155, 158) can be determined by stimulation of afferent as well as descending axons. Finally, stimulation of the L, dorsal roots evokes stepping movements of the deafferented hindlimbs in the acute spinal cat after injection of Clonidine or dopa (sect. VII). Increase of the stimulation strength results in an increase of the frequency of stepping because of shortening of the extensor bursts, Thus, some tonic influence appears to be necessary for activation of the automatism of stepping in the acutely isolated spinal cord. In the intact cat, such activation is performed by tonic descending influences. In experimental conditions, such activation can be obtained by injection of dopa or Clonidine as well as by tonic afferent inflow. Cyclic afferent inflow is not necessary for the generation of all cyclic reciprocal activity of flexors and extensors, but often its role becomes crucial. In chronic spinal animals, the mechanism generating stepping of the hindlimbs can work without additional tonic activation. Probably in this case stepping is enhanced due to degeneration of some descending pathways. In


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the opossum (even though it is taxonomically distant from the dog), stepping of the hindlimbs appears also only some days after spinalization (77). One can suppose that generation of stepping begins when certain spinal neurons are activated. At rest these neurons could be either inactive or inhibited by another group of neurons. In the latter case, descending influences would produce locomotion by inhibiting these inhibitory neurons. This seems to be likely, since in the mesencephalic cat with relatively caudal section of the brainstem (sect. VI), stepping cannot be evoked either on a moving treadmill band or even by MLR stimulation, but after section of the spinal cord at a low thoracic level (but not after deafferentation of the hindlimbs) the forelimbs begin stepping on the moving band (25). All these observations suggest that the mechanism generating stepping movements of the forelimbs is tonically inhibited by some structures in the caudal spinal cord. One may suppose that the same structures also inhibit the mechanism generating stepping in the hindlimbs. The above supposition is compatible with the observation that strychnine [which in a subconvulsive dose depresses transmission in many inhibitory synapses of the spinal cord (34a)] facilitates stepping movements of the hindlimbs in the chronic spinal dog (76, cited in 67; 116) and in the spinal rat (180). The eff ec t of s t rye h nine is hardly in accord with hypotheses suggesting a key role for inhibitory neurons in the spinal automatism of stepping (sect. XII@. If the main source of tonic inhibition of the automatism of stepping is located in the spinal cord, inhibition of this source by descending influences would release the automatism of stepping. Note in this connection that electrophoretic microapplication of norepinephrine exerts inhibitory action on some inhibitory spinal neurons (at least on Renshaw cells) (41). There is also at present some evidence for reticulospinal neurons with monosynaptic inhibitory action on spinal cord neurons (81, 87, 198). In primitive chordates [amphioxus (153, 182, as cited in 67) and dogfish (62, 66, 142)], section of the spinal cord results in continuous swimming movements that can be intensified by exteroceptive stimulation. As undulations propagate along the body with higher speed, the duration of the muscle activity in the individual somites decreases accordingly (66). In amphibians, stepping movements do not arise spontaneously after spinalization, but they can be elicited by rotation of a drum on which the feet of a fixed animal are placed (60). Probably, in these animals the spinal automatism of locomotion is not suppressed by spinal structures. XI.

INTERLIMB

COORDINATION

Dependence between movements of different limbs during locomotion is weaker than between the joints of one limb, but nevertheless it is stronger than at rest. This can be seen in experiments on the intact dog running on a treadmill. If the animal is suspended so that only one limb is on the moving band, this limb performs stepping movements. A short-term arrest of the


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limb results in the phase displacement when the released limb begins stepping again (161). However, when two limbs of one girdle are walking (or, of course, if all four limbs participate), arrest of one of them does not strongly influence the second one. When released, the restrained limb regains correct phase relations with the second one. When two forelimbs are walking on the band, the suspended hindlimbs perform stepping movements in the air with the same rhythm, but if the hindlimbs are walking on the band, the suspended forelimbs do not move (161). Corresponding results were obtained in experiments on the mesencephalit cat (97, 162). The influence of the hindlimbs on the forelimbs is weaker than the reverse but it nevertheless exists, since with MLR stimulation the hindlimbs usually begin stepping first and the forelimbs join them after some steps. Deafferented hindlimbs begin stepping some cycles later than the forelimbs (with intact innervation) (162). In addition to the central program (sect. IV), crossed extensor reflexes (156, 157) can also take part in coordination of the limbs of one girdle, in particular the “Reflexumkehr” phenomenon (110). In the spinal cat after dopa injection, stimulation of the FRA evokes long-lasting (several hundreds of milliseconds) reciprocal activity of ipsilateral flexor and contralateral extensor motoneurons (88, 89). Both responses resemble activity of motoneurons during stepping. The role of afferent inflow in coordination of the limbs of one girdle can be estimated in experiments with a double treadmill on which, during evoked locomotion in the mesencephalic cat, left and right limbs walk on two bands moving independently (97). If the band speeds differ by a factor of 2, the left and right hindlimbs exhibit equal cycle durations. This cycle duration is shorter than it would be if both bands moved with the speed of the slower band, but it is longer than would be the case if the bands moved with the speed of the faster one. The limb stepping on the rapid band has a longer swing phase and shorter stance phase than the limb stepping on the slow band. However, if the band speeds differ by a factor of 4-6, the limb stepping on the rapid band sometimes performs two steps for every step of the “slow” limb (97). Similar results have been obtained in the spinal animal (67). Coordination between the fore- and hindlimbs is difficult to explain by simple interlimb reflexes, because both the phase shift and the time lag between their movements depend on the speed of locomotion. However, in the intact cat, the time lag between knee extension and flexion of the ipsilateral elbow is constant (about 40 ms) at any speed higher than 1.4 m/s (113). This time lag can be explained by ascending propriospinal reflexes (113). Reflexes in forelimb muscles evoked by stimulation of hindlimb afferents are facilitated after dopa injection (in the high spinal cat) (14) and during MLR stimulation (in the curarized mesencephalic cat) (24). In the latter case, facilitation occurs even with weak MLR stimulation that does not affect the segmental reflexes. There is also another approach to the problem of coordination between the fore- and hindlimbs in diagonal gait. It can be achieved, at least in a


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certain range of speeds, by linkage between “turning points” in the cycles of from extensor to flexor the fore- and hindlimbs (67); i.e., the transition activity in the forelimb coincides in time (with an accuracy of some dozens of milliseconds) with the transition from flexor to extensor activity in the hindlimbs. A more general model of interlimb coordination during locomotion is described elsewhere (161). Descending (54, 101) and ascending (114) reflexes can be mediated by propriospinal pathways. These long propriospinal reflexes can be either of short or of long latency (54, 101, 114) and can be either excitatory or inhibitory (114). Short-latency facilitatory reflexes are observed only in the proximal muscles of the shoulder girdle (114). In other muscles of the forelimb only weak and variable long-latency reflexes are observed, but these can be enhanced by strychnine (54). Spinobulbospinal (54, 167, 168) and spinocerebellovestibulo (reticula-, rubro-) spinal reflexes (sect. IX) probably also take part in interlimb coordination. However, descending pathways of these reflexes may be involved also in supraspinal regulation of movements of a single limb and even of individual muscles. Therefore, it seems better to consider these two reflex systems as not specialized for interlimb coordination but rather as a part of the equilibrium automatism used in locomotion. This automatism can process (in accordance with the brainstem-cerebellar program for equilibrium) not only the inflow from the limb receptors and from the spinal automatisms of stepping, but also the inflow from the labyrinthine, neck, and distant receptors. Thus, two mechanisms would be responsible for interlimb coordination: 1) interaction between the spinal automatisms of stepping (where each automatism receives the afferent inflow only from its “own” limb) and 2) interlimb reflexes that do not affect the automatisms of stepping but influence directly the motoneurons. One can suggest that the vestibular reflex system participates in control of equilibrium during locomotion, since head movements during locomotion are large enough to activate the vestibular receptors (175). It has also been supposed that vestibular receptors might control the rhythm and activity of limb muscles during jumping in man (112). However, during evoked locomotion in the mesencephalic cat, responses of the main descending pathways to natural vestibular stimulation are diminished (128, 130). It is possible that the more essential role in control of equilibrium during locomotion belongs to the neck reflexes. This suggestion is based on the observations of Brown, who first studied locomotion of the precollicular cat on the treadmill [Lundberg and Phillips (lO7)]. XII.

HYPOTHESES AUTOMATISM

ON OF

ORGANIZATION

OF

SPINAL

STEPPING

A theory of the spinal automatism of stepping must explain the following main experimental data: 1) Muscles of the limb are cyclically activated in a fixed order independ-


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ent of the speed of locomotion (36, 51). Two main groups of musclesextensors and flexors -are active in approximate alternation. Some two-joint muscles are either active in the phases that do not coincide with those of the main groups or they are active twice per cycle. 2) The durations of the stance phase and of the associated extensor muscle activity vary over a severalfold range in accordance with the speed of locomotion, whereas the durations of the swing phase and of corresponding flexor activity depend only weakly on locomotor speed (10, 162). 3) The relative durations of the swing and stance phases in a particular limb are affected mainly by the afferent inflow from the same limb, whereas the overall duration of the step cycle depends significantly on inflow from the symmetric limb as well (67, 97). 4) The brain can influence directly the degree of muscular activity but not the duration of the step cycle, which can be changed only if the speed of locomotion changes. Some brain centers -for example, the SLR and MLRsimultaneously change activity of all limb muscles (162); others (reticulospinal, vestibulospinal, rubrospinal, and pyramidal systems) can influence activity in particular muscle groups more specifically (121). 5) In the spinal cat (after dopa injection) the hindlimb can perform stepping movements both in the normal forward direction and also backward, depending on the direction of the treadmill band (23). 6) Rhythmic reciprocal activity of flexors and extensors can be evoked even in a deafferented limb (19, 72, 134). Of course this list is not complete. It is also necessary to note that some points included have been observed in the mesencephalic cat but not in the spinal preparation. A. Chain-Reflex Hypothesis The main idea of the chain reflex hypothesis of locomotion control can be formulated as follows (139). Contraction of one muscle group results in a signal for contraction of another group and so on until the entire step cycle is completed. For example, one can suggest that the swing phase should begin when a certain angle of extension at the shoulder (or hip) joint is achieved. This specific suggestion seems to be confirmed in experiments on the intact dog suspended above the moving treadmill band so that only one forelimb performs stepping movements. Under such conditions, the duration of the stance phase increases if the dog is raised away from the band so that its stepping limb becomes less flexed and “longer” (161). At a constant speed of the band, the shoulder angle reaches the apparent threshold value later in the cycle, and the swing phase begins later as well. However, rhythmic reciprocal activity of flexors and extensors can be evoked even in the deafferented limb and deafferented hindlimbs take part in locomotion if the forelimbs walk (162, 181). Hence afferent inflow from the stepping limb is not a necessary condition for stepping, although it plays a very important role in intact animals.


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Gray (59) modified the original chain-reflex hypothesis by advancing the idea of “nonspecific” cyclic afferent inflow. Indeed, stepping movements of a deafferented limb of a mammal can hardly be distinguished from those of the intact limbs provided any one of the dorsal roots taking part in the innervation of that limb is left intact. However, after complete deafferentation stepping is disturbed. Locomotion of the toad after complete deafferentation of the spinal cord can hardly be elicited, although this is possible if any pair of the dorsal roots is left intact (59, 61). Thus, Gray’s supposition has some experimental support. However, it remains unknown why a nonspecific cyclic afferent inflow plays an important (sometimes decisive) role in the generation of stepping. It is worth noting that Gray’s point of view suggests that an intraspinal program is much more important for stepping than was suggested in the original chain-reflex hypothesis. B. Reciprocal

Half-Center

Hypothesis

The first attempt to explain a rhythmical process as originating within the spinal cord was made by Graham Brown in his hypothesis about inhibitory interaction between two “half-centers” (21). To explain rhythmical reciprocal activity of antagonistic muscles, a process similar to fatigue was postulated to occur in the active half-center. Naturally, Brown’s theory, developed to explain the generation of a rhythmic output within the spinal cord in the absence of rhythmic afferent inflow, cannot explain the disproportional change of durations of the swing and stance phases when the speed changes. Lundberg and his colleagues have accepted Brown’s hypothesis of two reciprocal half-centers as a basic rhythm generator and have supplemented it by a careful analysis of the modulating effect of various proprioceptive reflexes. These workers obtained the first direct evidence about a segmental interneuronal network that could be a substrate for spinal stepping. They further showed the significance of nonspecific tierent inflow from the flexor reflex tierents (FRA) to this network. They found in the lumbar spinal cord of the cat a group of interneurons in which the response to FRA stimulation changes dramatically after dopa injection; long-lasting discharges appeared, according to which these neurons could be divided into two reciprocally organized subgroups (89). Such interneurons might play an important role in the generation of stepping. They are localized in the dorsolateral part of the ventral horn (89), a region where large numbers of degenerated cells have been found after temporary spinal cord ischemia (52, 53). Such animals cannot walk or perform any other phasic movements with the hindlimbs, which become rigid (“asphyxial rigidity”). It is also in this region that large numbers of cyclically modulated neurons have been found during evoked locomotion in the mesencephalic cat with deafferented hindlimbs (127). However, the suggested central program generating reciprocal output in flexors and extensors also has to explain the timing of activity of some muscles that cannot be referred directly to these groups. It has been found that proprioceptive inputs to motoneurons of these other muscles are orga-


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nized (103) so that “atypical” activity of these muscles can be explained with these data (36, 104) together with data about fusimotor modulation of the spindle afferents during locomotion (sect. x). In Lundberg’s laboratory, neurons mediating inhibition from la afferents to antagonistic motoneurons have been identified and studied extensively (81, 100, 105). These inhibitory interneurons mediate also vestibulospinal influences to flexor motoneurons (68) and propriospinal descending influences on motoneurons (90). The background activity of these la inhibitory interneurons (82, 197) and that of the motoneurons supplied by the same la afferents are both inhibited by Renshaw cells (81). Therefore, the activity of the system of reciprocal la inhibition depends on the level of motoneuron activity: the more motoneurons generate spikes, the stronger will Renshaw cells inhibit la inhibitory interneurons; inhibitory influences on antagonistic motoneurons mediated by these interneurons become correspondingly weaker. However, if motoneurons and inhibitory interneurons (projecting to the antagonistic motoneurons) are activated in parallel, as in the case of la afferent inflow, reciprocal inhibition would not change when activity of motoneurons increases (83). A direct study of la inhibitory interneurons in the lumbar spinal cord during MLR stimulation in the mesencephalic cat showed that their activity is cyclically modulated even when the hindlimbs are de-efferented and do not move (45). They are maximally active in the phase when motoneurons of antagonistic muscles are inhibited (i.e., antagonistic to muscles that are the source of la input). It seems likely that la interneurons make a considerable contribution to this inhibition. Their contribution increases if the limb is not de-efferented, and the spindle afferents enhance activity of la interneurons (45). Thus, la interneurons and ar-motoneurons excited by la afferents of the same muscle, plus homonymous y-motoneurons, are all activated in phase by the central generator. Hence, during locomotion, the central excitatory drive to la interneurons is apparently stronger than the inhibitory influence from Renshaw cells. Probably, Renshaw cells are inhibited during locomotion, since recurrent inhibition of motoneurons diminishes both during locomotion (150) and after dopa injection (13). Recurrent inhibition of la inhibitory interneurons is also diminished during locomotion (45). Each of the two classic hypotheses of spinal stepping can explain only part of the experimental findings. The chain-reflex hypothesis is sufficient to explain the dependence of limb movements on the speed and external condition of locomotion. On the other hand, the hypothesis of two reciprocal halfcenters explains stepping of the deafferented limb. Attempts have been made by Gray and by Lundberg to formulate a synthesis of these two ideas, but so far a complete theory has not been developed. C. Ring Hypothesis We shall consider one more hypothesis of the spinal automatism of stepping in an attempt to explain on a common basis the various experimen-


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tal data. This “ring” hypothesis (74) is presented in some detail not because it has special advantages, but because it has not been discussed in detail elsewhere. The main suppositions are as follows. 1) There exists a ring circuit (Fig. 2) consisting of many successive neurons, and any cross section of the ring also contains many neurons. The rings controlling hindlimb muscles can be localized within the upper lumbar segments [like the neurons mediating corticospinal influences (96) or cells of the ventral spinocerebellar tract]. Such a localization is suggested by Brown’s early observations (20) and by the data showing a prominent role in stepping for proprioceptors located in the proximal part of the limb, which seem to enter the spinal cord mainly at the upper lumbar level. Nevertheless, neurons of the ring can be distributed throughout the lumbosacral spinal cord. 2) Neurons of the ring are assumed to project to the motoneurons of various limb muscles either directly or through specific interneurons. The sequence of these projections determines the order of activation of various muscles in the step cycle and the cyclic modulation of excitability of interneurons of the short-latency segmental reflexes. 3) The velocity of propagating excitation in any small ring segment depends on the excitability of its neurons and on the number of active neurons in the “previous” small segments. In various cross sections of the ring, the numbers of neurons are assumed to be different. Therefore, the velocity of propagation would be different in various segments. The “road” can be especially broad in two parts of the ring: i.e., in those ring segments repreDESCENDING

INFLUENCES

MOTONEURONS

NONGENERATOR

NONGENERATOR

MOTONEURONS

MOTONEURONS

MOTORNEURONS BIFUNCTIONAL FIG.

2. Ring

hypothesis

of spinal

automatism

OF

MUSCLES

of stepping

limb.


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senting the transitions from the stance to swing phase and vice versa. The durations of these transitional phases of the step are short since the velocity of propagation in corresponding segments is high due to spatial and temporal summation in relatively large numbers of cells. 4) The overlap between the axonal and dendritic arborizations of neurons belonging to adjacent segments of the ring is presumed to be nonsymmetric. Therefore, the velocity of propagation of the excitatory wave in the backward direction would be lower than in the normal forward one. 5) At rest the functional ring circuit disappears, since its neurons (or at least neurons in some segment) are inhibited. Therefore, there is no cyclic activity. Activation of the ring neurons is determined by the adjacent ring neurons as well as by the descending and afferent inflow. Tonic influencesboth descending and afferent - can restore the active ring circuit and increase the degree of activity of its neurons to a level near the threshold for propagation of excitation. However, without cyclic inflow, cyclic activity in the ring is assumed to be just possible. 6) An external excitatory inflow is essential especially in that phase of the cycle when the wave is propagating along the most “narrow” segment of the ring. This would be the segment representing the stance phase, and the velocity of propagation in this phase depends considerably on an additional excitatory inflow. Cyclic inflow appropriately phased is much more effective than tonic. The latter would be either insufficient to facilitate propagation of the wave through the narrow segment or, if potent, it would excite too many neurons in the broader segments. If an inflow is tonic, the direction of propagation in the ring depends only on the postulated asymmetrical interconnections of neurons of the adjacent ring segments. But a cyclic inflow can result in a marked gradient of excitability along the ring, promoting unidirectional propagation of excitation along the ring. Thus, cyclic afferent inflow to the ring would be very important for stable cyclic activity of the generator. 7) The velocity of propagation of excitation depends on the afferent inflow, at least during the stance phase. This can lead to synchronization and phase coupling between activity of the ring and the cyclic afferent input. The source of cyclic afferent inflow would not be too important. However, in normal conditions, the main source of cyclic afferent inflow is the homonymous limb. Its stepping movements are determined by the ring and therefore establishment of proper phase relations between ring activity and movements of the limb is a mutually dependent process with rapid development. This would be a mechanism for quickly adapting the cycle duration to the speed of locomotion. 6) The ring hypothesis is compatible with a system of reciprocal interaction between antagonistic motoneuron pools. This interaction is believed to be mediated by specific interneurons and would not interfere with the process within the ring. The ring hypothesis can also be supplemented with a system of various specific proprioceptive influences on motoneurons, but both reciprocal and proprioceptive systems are themselves not sufficient to produce


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stepping, although they take part in stepping as they also do in various other types of movements. 9) At rest a number of ring neurons are tonically inhibited by a certain group of spinal neurons. Activation of the monoaminergic descending system results in inhibition of the inhibitory neurons with consequent disinhibition of the ring neurons. 10) The ring can consist of excitatory neurons, but participation of inhibitory ones cannot be excluded. Any section of the ring must contain many neurons, and it is not a chain of single successive neurons. Such linear reverberatory cycles have been postulated as a mechanism for generating slow rhythms but have not yet been demonstrated in the mammalian central nervous system. Summation of excitation based on the convergence of many neurons from one small segment onto neurons of an adjacent small segment is an essential feature of the ring hypothesis. A formal model of a linear closed chain consisting of inhibitory neurons was proposed and well investigated by Kling and Szekely (95, 177). Their work demonstrated some advantages of the cyclic model in comparison to the reciprocal one, but the model fails to explain some facts-for example, the disproportionate change in the durations of the swing and stance phases when the speed of locomotion varies. The ring hypothesis is in agreement with the fact that during locomotion the limb is controlled as a unit. To achieve the same effect with the model of two reciprocal half-centers one must suggest that each half-center simultaneously influences all limb extensors (or flexors). The hypothesis of multiple microcycles (178) also must be supplemented by some special mechanism to explain the unity of the stepping limb. XIII.

CONCLUSION

It has long been known that the decapitated cock can cross a yard. During the last century an automatic mechanism controlling stepping movements has also been found in other vertebrates. The system controlling locomotion has many features similar to these systems controlling other natural movements: respiration (28), micturition (98), scratching (154), mastication (33), etc. Today we know that there are spinal automatisms for each limb generating its stepping movements. Activity of these automatisms depends essentially on the afferent inflow from the moving limbs. There also is interaction of the limbs during locomotion that promotes their coordination. The existence of two descending systems with different functions in the control of locomotion (Fig. 1) also can be considered as an established fact. Activity of a number of neurons involved in the control of locomotion has been studied directly during locomotion in decorticate, thalamic, and mesencephalit cats. To explain the experimental data at hand, several hypotheses of organization of the spinal automatism of stepping have been forwarded: a chain-reflex hypothesis, a hypothesis of two reciprocal half-centers, and a ring hypothesis (Fig. 2).


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Although general features of the system controlling locomotion are more or less clear, many questions are not yet answered. It is unknown what relative contributions to motoneuronal activity are made by proprioceptive reflexes versus influences from the automatism of stepping. Furthermore the structure of the spinal stepping automatism is not known. It is not clear if the spinal stepping automatisms of the forelimbs are as potent as those of the hindlimbs. The descending system responsible for activation of the spinal automatism of stepping has not yet been identified in direct experiments. The inputs and outputs of the subthalamic and midbrain “locomotor” regions have not been found, and we know almost nothing about intrinsic interaction of neurons in these regions. The role of inhibitory thalamic influences is scarcely known. Finally, we have no data concerning the influence of either cortical (42, 186) or visual mechanisms in locomotor control. We thank manuscript.

Dr.

R. Burke

for helpful

comments

and for assistance

during

preparation

of the

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