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Localization of a descending pathway in the spinal cord which is necessary for controlled treadmill locomotion
Neuroscience Letters, 20 (1980) 283-288
283
© Elsevier/North-Holland Scientific Publishers Ltd.
L O C A L I Z A T I O N OF A D E S C E N D I N G P A T H W A Y IN T H E S P I N A L CORD W H I C H IS NECESSARY FOR C O N T R O L L E D T R E A D M I L L L O C O M O T I O N
JOHN D. STEEVES* and LARRY M. JORDAN**
Department of Physiology, University of Manitoba, Faculty of Medicine, Winnipeg R3E OW3 (Canada) (Received May 27th, 1980; Revised version received August 14th, 1980; Accepted August 14th, 1980)
The spinal cord pathways which are important for controlled treadmill locomotion evoked by stimulation of the mesencephalic locomotor region (MLR) were investigated in cats subjected to subtotal spinal cord lesions at the C1-C2 level. Locomotion could be evoked following bilateral lesions of the dorsal columns, the dorsolateral funiculi, and the ventromedial funiculi, and after combined lesions of the dorsolateral and ventromedial funiculi, but not after bilateral lesions of the ventrolateral quadrant. Unilateral lesions of the ventrolateral quadrant abolished locomotion in the limbs ipsilateral to the lesion. It is suggested that MLR stimulation may give rise to locomotion by activation of pontine and medullary reticulospinal pathways projecting through the ventrolateral quadrant.
Recent studies in decerebrate cats have shown that repetitive stimulation of a discrete brain stem area below the inferior colliculus, the mesencephalic locomotor region (MLR), gives rise to locomotion [16] even in the absence of cyclic afferent input [6]. However, little is known about the projections from the brain stem to the spinal cord which are essential for the initiation of MLR-evoked locomotion. This question was examined by locating the MLR in decerebrate cats, and then selectively disrupting specific areas of the spinal cord at the cervical level ( C I - C 2 ) during a transient regional cold block. After a recovery period, the response to MLR stimulation was re-examined. The details of the decerebration procedure and MLR stimulation parameters have been previously described [18, 19]. Briefly, cats were anesthetized with a mixture of halothane and nitrous oxide; the animal was placed in a stereotaxic device above a treadmill, and a laminectomy (C1-C3) was performed. The animal was decerebrated with a spatula along a plane extending from the rostral border of the superior colliculus dorsally to the caudal border of the mammillary bodies ventrally (a 'postmammillary' preparation). Locomotion was evoked through a monopolar stimulating electrode positioned in either the right or left MLR by a 30 Hz stimulus * Present address: Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, V6T 2A9, Canada. ** To whom correspondence should be addressed.
284
train (0.5 msec duration/pulse; 50-125/~A). The M L R was localized using surface landmarks as previously described [18, 19]. Electromyographic (EMG) recordings from both hip flexor (iliopsoas) and hip extensor (adductor femoris) muscles were amplified and recorded on a polygraph. Hindlimb excursions were recorded by a potentiometer attached through a lever to the ankle. After establishing the optimal M L R electrode tip position at which the lowest stimulation strength could evoke coordinated walking, the C I - C 2 spinal cord was cooled by applying small blocks of frozen saline directly to the cord. Cooling was maintained until the extensor rigidity of the fore- and hindlimb disappeared, and the beginning of apnea occurred. This signalled blockage of spinal cord transmission, which allowed the spinal lesions to be administered without the excessive neuronal stimulation which accompanies manipulation of the spinal cord in the absence of cold block. Attempts to perform the lesions in the absence of cold block resulted in decreased blood pressure with depressed spinal cord reflexes and were often fatal. The animal was artificially respired during the period of cold block. Various combinations of partial transections of the C 1 - C 2 spinal cord were made with the use of microdissecting scissors, except for the sectioning of the ventral funiculus. To section the ventral funiculus, a sharp probe was inserted through the dorsal columns at the midline. Artificial respiration was maintained in animals which did not breathe spontaneously after recovery from the cold block. Animals were allowed to recover for 1 - 2 h before MLR stimulation was resumed. At the end of the stimulation trials, the cervical spinal cord was removed and 30 ttm serial crosssections of the C I - C 2 cord were cut on a cryostat. The sections were stained with 0.1% cresyl violet stain using standard histological techniques and examined under a microscope. Drawings of representative cross-sections of the C 1 - C 2 cord were made detailing the sites of the lesions. Fig. 1 illustrates the locomotion before (A) and after (B) transection of the dorsolateral quadrants of the spinal cord. The locomotion illustrated in Fig. IB was obtained with an increase in the M L R stimulus strength of 25 , A , an increase which is within the range of threshold fluctuations during control trials. This figure serves to illustrate that the dorsolateral funiculus is not essential for MLR-evoked treadmill locomotion, and that full recovery of evoked locomotion can occur after certain lesions. Fig. 2 summarizes the bilateral lesions which were used in this study. It is clear that the only restricted area of the white matter that is essential for MLR evoked treadmill locomotion is the ventrolateral quadrant. Transections of the dorsolateral quadrants (n -- 2), dorsal columns (n = 2), and ventromedial funiculus (n = 3) were without effect. When the entire dorsal cord was transected (n = 2), locomotion could be evoked by M L R stimulation, but only at high current strengths (>_ 200 t~A). Similarly, a combined lesion of the dorsolateral and ventromedial funiculi did not abolish locomotion, but large current strengths were required for its initiation.
285
R. hip ext. R. hip fl. R.(flexiont)//~/'~//'~j/" L.(flexiont)~ , / ~ / ~ / ~ " ~
~
R. hip ext. R.hip fl. ~ ¢ I H ~ ¢ R.(f l e x l o n t ) ~ L. (flexiont)/~ ~ f ~
uE ]o
~.o ~& Fig. 1. MLR-evoked treadmill locomotion before (A) and after (B) bilateral lesions of the dorsolatera[ funiculus. EMG records are from the right adductor femoris (R. hip ext.) and right iliopsoas (R. hip fl.). The lower traces show the horizontal displacements of the right and left hindlimbs during evoked treadmill locomotion. The sites of the lesions are illustrated in the diagram on the left in B.
OCO OTO
NO LOCOMOTION Fig. 2. Summary of the bilateral lesions used in this study. Those which did not abolish locomotion are illustrated at the top of the figure (Locomotion), and those which did abolish locomotion are illustrated below (No Locomotion).
Bilateral d i s r u p t i o n o f the fiber pathways coursing t h r o u g h the ventrolateral q u a d r a n t s (n = 5) consistently abolished all M L R evoked l o c o m o t i o n . P r i o r to t r a n s e c t i o n every a n i m a l was c a p a b l e o f c o o r d i n a t e d q u a d r a p e d a l l o c o m o t i o n . After severing the v e n t r o l a t e r a l q u a d r a n t s , M L R s t i m u l a t i o n with currents o f up to 500 # A was totally ineffective. Not surprisingly, t r a n s e c t i o n o f the entire v e n t r a l cord (n = 2) a n d t r a n s e c t i o n o f the entire C 1 - C 2 cord except for the v e n t r o m e d i a l funiculus (n = 1) also abolished M L R evoked l o c o m o t i o n .
286
As shown in Fig. 3A, stimulation of the left or right MLR in cats with a hemisection of the C I - C 2 cord (n = 2) led to stepping only with the limbs contralateral to the side of the hemisection. Identical results were obtained from animals in which only one ventrolateral quadrant (n = 2) was transected (Fig. 3B). In acute spinal animals, the cross-sectional areas of the cord where stimulation most effectively produces hindlimb stepping are the dorsal columns and the d0rsolateral funiculi [4, 8, 15, 17]. However, in the present study, the interruption of fiber pathways which project through these areas does not abolish the locomotion evoked by MLR stimulation. Likewise, the ventromedial funiculus does not appear to be essential or sufficient for evoked locomotion in the postmammillary cat. This finding does not support previous reports [1, 21] that the ventromedial funiculi are essential for locomotion in chronic lesioned animals. A possible explanation might be that the locomotion observed in the previous studies which implicated the ventromedial funiculus was actually spinal stepping. The area of the spinal cord which appears to be essential for MLR evoked treadmill locomotion is the ventrolateral quadrant. This is supported by Eidelberg's finding (personal communication) that the capacity for locomotion is retained to the greatest extent when the ventrolateral quadrant is spared in cats with chronic subtotal spinal cord lesions, by a report [5] of involuntary stepping movements in humans with spinal injuries which spared parts of the ventral spinal cord, and by
ul
R. hip e x t . . ~ t ~ l - ~
R. hip f l
L.hip ext.
L. hip fl.
R.(flexion t ) ~ / ~ / ~ / ~ f
R.(flexion t)
L.(flexiont)
L.(flexion t 1,O
)
~
E ]~
sec
Fig. 3. Effects on MLR-evoked treadmill locomotion of spinal cord hemisection (A) and a unilateral lesion of the ventrolateral funiculus (B). E M G records in A are from the right and left adductor femoris (R. hip ext. and L. hip ext.); those in B are from the right and left iliopsoas (R. hip fl. and L. hip ft.). Potentiometer records showing horizontal excursions of the two hindlimbs are shown in the bottom traces.
287 Shik's finding (personal communication) that lesions of the lateral funiculus abolish ipsilateral stepping. This study does not establish which of the pathways descending in the ventrolateral quadrant are essential for evoked treadmill locomotion, but several possibilities must be considered. Fibers from the nucleus locus coeruleus and nucleus subcoeruleus project via the ventrolateral quadrant [7], and noradrenergic fibers originating from these nuclei have been implicated in the initiation of locomotion [18]. However, depletion of spinal norepinephrine is without effect on MLR-evoked locomotion [19]. Similarly, some fibers from the serotonergic raphe complex traverse the ventrolateral quadrant [3, 7, 9], but depletion of serotonin from the spinal cord does not alter MLR-evoked locomotion [19]. The lateral vestibular complex also projects to spinal levels via the ventrolateral quadrant [7], and destruction of Deiter's nucleus has been reported to result in cessation of MLRevoked stepping ipsilateral to the lesion [13]. In addition, stimulation of the vestibular complex can disturb the locomotor rhythm [14]. Moreover, neurons of one of the ascending pathways in the ventrolateral quadrant, the ventral spinocerebellar tract, have been shown to be rhythmically active during locomotion even after deafferentation or removal of the cerebellum [2]. Whether the integrity of the vestibulospinal or ventral spinocerebellar pathway is necessary for the initiation of locomotion remains to be elucidated. The fact that dorsolateral funiculus stimulation produces locomotion in spinal animals suggests that multiple pathways in the spinal cord white matter may be important for the initiation of locomotion. In addition, a propriospinal component is suggested by Shik's finding (personal communication) that MLR-evoked locomotion can be abolished by lesions in Rexed's laminae V-VIII extending throughout segments C2-C3. Nevertheless, a plausible hypothesis, first proposed by Orlovsky [12], is that portions of the medial pontine and medullary reticular formation which project to the spinal cord through the ventrolateral funiculus [3, 7, 10, 20] play a role in the initiation of locomotion. Anatomical and electrophysiological evidence suggests that cells in the MLR project to reticulospinal neurons in these regions [12, Steeves and Jordan, unpublished observations]. Furthermore, stimulation in these same areas of the reticular formation can produce locomotion in post-mammillary cats [11]. Anatomical evidence indicates that cells in the region of the MLR do not project to the spinal cord (Steeves and Jordan, unpublished observation); thus, the initiation of locomotion by MLR stimulation may be via a pathway from the MLR to the pontine and medullary reticulospinal areas.
We thank Dr. E. Eidelberg and Dr. P.S.G. Stein for reading a draft of the manuscript, and Janet Greer for typing it. Supported by the Medical Research Council of Canada.
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Afell, Z., Functional significance of ventral descending tract of the spinal cord in the cat, Acta neurobiol, exp., 34 (1974) 393-40?. Arshavsky, Yu.l., Berkinblit, M.B., Fukson, O.I., Gelfand, I.M. and Orlovsky, G.N., Origin of modulation in neurones of the ventral spinocerebellar tract during locomotion, Brain Res., 43 (1972) 276 279. Basbaum, A.I., Clanton, C.H. and Fields, H.L., Three bulbospinal pathways from the rostral medulla of the cat: an autoradiographic study of pain modulating systems, J. comp. Neurol., 178 (1978) 209-224. Grillner, S. and Zangger, P., Locomotion movements generated by the deafferented spinal cord, Acta physiol, scand., 91 (1974) 38A-39A. Holmes, G., Spinal injuries of warfare. II. The clinical symptoms of gunshot injuries of the spine, Brit. med. J., 2 (1915) 815-821. Jordan, L.M., Pratt, C.A. and Menzies, J.E., Locomotion evoked by brainstem stimulation: occurrence without phasic segmental afferent input, Brain Res., 177 (1979) 204-207. Kuypers, H.G.J.M. and Maisky, V.A., Funicular trajectories of descending brain stem pathways in the cat, Brain Res., 136 (1977) 159-165. Lennard, P.R. and Stein, P.S.G., Swimming movements elicited by electrical stimulation of the turtle spinal cord. I. Low-spinal and intact preparations, J. Neurophysiol., 40 (1977) 768 778. Martin, R.F., Jordan, L.M. and Willis, W.D., Differential projections of cat medullary raphe neurons demonstrated by retrograde labelling following spinal cord lesions, J. comp. Neurol., 182 (1978) 77-88. Martin, G.F., Humberston, A.O., Laxson, L.C., Panneton, W.M. and Tschismadia, 1., Spinal projections from the mesencephalic and pontine reticular formation in the north American opossum: a study using axonal transport techniques, J. comp. Neurol., 187 (1979) 373-400. Mori, S., Nishimura, H., Kurakami, C., Yamamura, T. and Aoki, M., Controlled locomotion in the mesencephalic cat: distribution of facilitatory and inhibitory regions within the pontine tegmentum, J. Neurophysiol., 41 (1978) 1580-1591. Orlovsky, G.N., Connections of the reticulo-spinal neurones with the 'locomotor sections' of the brain stem, Biofizika, 15 (1970) 171-177. Orlovsky, G.N., The effect of different descending systems on flexor and extensor activity during locomotion, Brain Res., 40 (1972) 359-371. Russell, D.F. and Zajac, F.E., Effects of stimulating Deiter's nucleus and medial longitudinal fasciculus on the timing of the fictive locomotor rhythm induced in cats by DOPA, Brain Res., 177 (1979) 588-592. Sherrington, C.S., Flexion-reflex of the limb, crossed extension-reflex, and reflex stepping and standing, J. Physiol. (Lond.), 40 (1910) 28-121. Shik, M.L., Severin, F.V. and Orlovsky, G.N., Control of walking and running by means of electrical stimulation of the mid-brain, Biofizika, 11 (1966) 756-?65 (English translation of Biofizika, 11 (1966)659-666). Shik, M.L. and Yagodnitsyn, A.S., The pontobulbar 'locomotor strip', Neurophysiologia, 9 (1977) 95-97. Steeves, .I.D., Jordan, L.M. and Lake, N., The close proximity of catecholamine-containing cells to the 'mesencephalic locomotor region' (MLR), Brain Res., 100 (1975) 663-670. Steeves, J.D., Schmidt, B.J., Skovgaard, B.J. and Jordan, L.M., Effect of noradrenaline and 5hydroxydopamine depletion on locomotion in the cat, Brain Res., 185 (1980) 349-362. Tohyama, M., Sakai, K., Salvert, D., Touret, M. and Jouvet, M., Spinal projections from the lower brain stem in the cat as demonstrated by the horseradish peroxidase technique. I. Origins of the reticulo-spinal tracts and their funicular trajectories, Brain Res., 173 (1979) 383-403. Windle, W.F., Smart, J.O. and Beers, J.J., Residual function after subtotal spinal cord transection in adult cats, Neurology (Minneap.), 8 (1958) 518-521.
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© Elsevier/North-Holland Scientific Publishers Ltd.
L O C A L I Z A T I O N OF A D E S C E N D I N G P A T H W A Y IN T H E S P I N A L CORD W H I C H IS NECESSARY FOR C O N T R O L L E D T R E A D M I L L L O C O M O T I O N
JOHN D. STEEVES* and LARRY M. JORDAN**
Department of Physiology, University of Manitoba, Faculty of Medicine, Winnipeg R3E OW3 (Canada) (Received May 27th, 1980; Revised version received August 14th, 1980; Accepted August 14th, 1980)
The spinal cord pathways which are important for controlled treadmill locomotion evoked by stimulation of the mesencephalic locomotor region (MLR) were investigated in cats subjected to subtotal spinal cord lesions at the C1-C2 level. Locomotion could be evoked following bilateral lesions of the dorsal columns, the dorsolateral funiculi, and the ventromedial funiculi, and after combined lesions of the dorsolateral and ventromedial funiculi, but not after bilateral lesions of the ventrolateral quadrant. Unilateral lesions of the ventrolateral quadrant abolished locomotion in the limbs ipsilateral to the lesion. It is suggested that MLR stimulation may give rise to locomotion by activation of pontine and medullary reticulospinal pathways projecting through the ventrolateral quadrant.
Recent studies in decerebrate cats have shown that repetitive stimulation of a discrete brain stem area below the inferior colliculus, the mesencephalic locomotor region (MLR), gives rise to locomotion [16] even in the absence of cyclic afferent input [6]. However, little is known about the projections from the brain stem to the spinal cord which are essential for the initiation of MLR-evoked locomotion. This question was examined by locating the MLR in decerebrate cats, and then selectively disrupting specific areas of the spinal cord at the cervical level ( C I - C 2 ) during a transient regional cold block. After a recovery period, the response to MLR stimulation was re-examined. The details of the decerebration procedure and MLR stimulation parameters have been previously described [18, 19]. Briefly, cats were anesthetized with a mixture of halothane and nitrous oxide; the animal was placed in a stereotaxic device above a treadmill, and a laminectomy (C1-C3) was performed. The animal was decerebrated with a spatula along a plane extending from the rostral border of the superior colliculus dorsally to the caudal border of the mammillary bodies ventrally (a 'postmammillary' preparation). Locomotion was evoked through a monopolar stimulating electrode positioned in either the right or left MLR by a 30 Hz stimulus * Present address: Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, British Columbia, V6T 2A9, Canada. ** To whom correspondence should be addressed.
284
train (0.5 msec duration/pulse; 50-125/~A). The M L R was localized using surface landmarks as previously described [18, 19]. Electromyographic (EMG) recordings from both hip flexor (iliopsoas) and hip extensor (adductor femoris) muscles were amplified and recorded on a polygraph. Hindlimb excursions were recorded by a potentiometer attached through a lever to the ankle. After establishing the optimal M L R electrode tip position at which the lowest stimulation strength could evoke coordinated walking, the C I - C 2 spinal cord was cooled by applying small blocks of frozen saline directly to the cord. Cooling was maintained until the extensor rigidity of the fore- and hindlimb disappeared, and the beginning of apnea occurred. This signalled blockage of spinal cord transmission, which allowed the spinal lesions to be administered without the excessive neuronal stimulation which accompanies manipulation of the spinal cord in the absence of cold block. Attempts to perform the lesions in the absence of cold block resulted in decreased blood pressure with depressed spinal cord reflexes and were often fatal. The animal was artificially respired during the period of cold block. Various combinations of partial transections of the C 1 - C 2 spinal cord were made with the use of microdissecting scissors, except for the sectioning of the ventral funiculus. To section the ventral funiculus, a sharp probe was inserted through the dorsal columns at the midline. Artificial respiration was maintained in animals which did not breathe spontaneously after recovery from the cold block. Animals were allowed to recover for 1 - 2 h before MLR stimulation was resumed. At the end of the stimulation trials, the cervical spinal cord was removed and 30 ttm serial crosssections of the C I - C 2 cord were cut on a cryostat. The sections were stained with 0.1% cresyl violet stain using standard histological techniques and examined under a microscope. Drawings of representative cross-sections of the C 1 - C 2 cord were made detailing the sites of the lesions. Fig. 1 illustrates the locomotion before (A) and after (B) transection of the dorsolateral quadrants of the spinal cord. The locomotion illustrated in Fig. IB was obtained with an increase in the M L R stimulus strength of 25 , A , an increase which is within the range of threshold fluctuations during control trials. This figure serves to illustrate that the dorsolateral funiculus is not essential for MLR-evoked treadmill locomotion, and that full recovery of evoked locomotion can occur after certain lesions. Fig. 2 summarizes the bilateral lesions which were used in this study. It is clear that the only restricted area of the white matter that is essential for MLR evoked treadmill locomotion is the ventrolateral quadrant. Transections of the dorsolateral quadrants (n -- 2), dorsal columns (n = 2), and ventromedial funiculus (n = 3) were without effect. When the entire dorsal cord was transected (n = 2), locomotion could be evoked by M L R stimulation, but only at high current strengths (>_ 200 t~A). Similarly, a combined lesion of the dorsolateral and ventromedial funiculi did not abolish locomotion, but large current strengths were required for its initiation.
285
R. hip ext. R. hip fl. R.(flexiont)//~/'~//'~j/" L.(flexiont)~ , / ~ / ~ / ~ " ~
~
R. hip ext. R.hip fl. ~ ¢ I H ~ ¢ R.(f l e x l o n t ) ~ L. (flexiont)/~ ~ f ~
uE ]o
~.o ~& Fig. 1. MLR-evoked treadmill locomotion before (A) and after (B) bilateral lesions of the dorsolatera[ funiculus. EMG records are from the right adductor femoris (R. hip ext.) and right iliopsoas (R. hip fl.). The lower traces show the horizontal displacements of the right and left hindlimbs during evoked treadmill locomotion. The sites of the lesions are illustrated in the diagram on the left in B.
OCO OTO
NO LOCOMOTION Fig. 2. Summary of the bilateral lesions used in this study. Those which did not abolish locomotion are illustrated at the top of the figure (Locomotion), and those which did abolish locomotion are illustrated below (No Locomotion).
Bilateral d i s r u p t i o n o f the fiber pathways coursing t h r o u g h the ventrolateral q u a d r a n t s (n = 5) consistently abolished all M L R evoked l o c o m o t i o n . P r i o r to t r a n s e c t i o n every a n i m a l was c a p a b l e o f c o o r d i n a t e d q u a d r a p e d a l l o c o m o t i o n . After severing the v e n t r o l a t e r a l q u a d r a n t s , M L R s t i m u l a t i o n with currents o f up to 500 # A was totally ineffective. Not surprisingly, t r a n s e c t i o n o f the entire v e n t r a l cord (n = 2) a n d t r a n s e c t i o n o f the entire C 1 - C 2 cord except for the v e n t r o m e d i a l funiculus (n = 1) also abolished M L R evoked l o c o m o t i o n .
286
As shown in Fig. 3A, stimulation of the left or right MLR in cats with a hemisection of the C I - C 2 cord (n = 2) led to stepping only with the limbs contralateral to the side of the hemisection. Identical results were obtained from animals in which only one ventrolateral quadrant (n = 2) was transected (Fig. 3B). In acute spinal animals, the cross-sectional areas of the cord where stimulation most effectively produces hindlimb stepping are the dorsal columns and the d0rsolateral funiculi [4, 8, 15, 17]. However, in the present study, the interruption of fiber pathways which project through these areas does not abolish the locomotion evoked by MLR stimulation. Likewise, the ventromedial funiculus does not appear to be essential or sufficient for evoked locomotion in the postmammillary cat. This finding does not support previous reports [1, 21] that the ventromedial funiculi are essential for locomotion in chronic lesioned animals. A possible explanation might be that the locomotion observed in the previous studies which implicated the ventromedial funiculus was actually spinal stepping. The area of the spinal cord which appears to be essential for MLR evoked treadmill locomotion is the ventrolateral quadrant. This is supported by Eidelberg's finding (personal communication) that the capacity for locomotion is retained to the greatest extent when the ventrolateral quadrant is spared in cats with chronic subtotal spinal cord lesions, by a report [5] of involuntary stepping movements in humans with spinal injuries which spared parts of the ventral spinal cord, and by
ul
R. hip e x t . . ~ t ~ l - ~
R. hip f l
L.hip ext.
L. hip fl.
R.(flexion t ) ~ / ~ / ~ / ~ f
R.(flexion t)
L.(flexiont)
L.(flexion t 1,O
)
~
E ]~
sec
Fig. 3. Effects on MLR-evoked treadmill locomotion of spinal cord hemisection (A) and a unilateral lesion of the ventrolateral funiculus (B). E M G records in A are from the right and left adductor femoris (R. hip ext. and L. hip ext.); those in B are from the right and left iliopsoas (R. hip fl. and L. hip ft.). Potentiometer records showing horizontal excursions of the two hindlimbs are shown in the bottom traces.
287 Shik's finding (personal communication) that lesions of the lateral funiculus abolish ipsilateral stepping. This study does not establish which of the pathways descending in the ventrolateral quadrant are essential for evoked treadmill locomotion, but several possibilities must be considered. Fibers from the nucleus locus coeruleus and nucleus subcoeruleus project via the ventrolateral quadrant [7], and noradrenergic fibers originating from these nuclei have been implicated in the initiation of locomotion [18]. However, depletion of spinal norepinephrine is without effect on MLR-evoked locomotion [19]. Similarly, some fibers from the serotonergic raphe complex traverse the ventrolateral quadrant [3, 7, 9], but depletion of serotonin from the spinal cord does not alter MLR-evoked locomotion [19]. The lateral vestibular complex also projects to spinal levels via the ventrolateral quadrant [7], and destruction of Deiter's nucleus has been reported to result in cessation of MLRevoked stepping ipsilateral to the lesion [13]. In addition, stimulation of the vestibular complex can disturb the locomotor rhythm [14]. Moreover, neurons of one of the ascending pathways in the ventrolateral quadrant, the ventral spinocerebellar tract, have been shown to be rhythmically active during locomotion even after deafferentation or removal of the cerebellum [2]. Whether the integrity of the vestibulospinal or ventral spinocerebellar pathway is necessary for the initiation of locomotion remains to be elucidated. The fact that dorsolateral funiculus stimulation produces locomotion in spinal animals suggests that multiple pathways in the spinal cord white matter may be important for the initiation of locomotion. In addition, a propriospinal component is suggested by Shik's finding (personal communication) that MLR-evoked locomotion can be abolished by lesions in Rexed's laminae V-VIII extending throughout segments C2-C3. Nevertheless, a plausible hypothesis, first proposed by Orlovsky [12], is that portions of the medial pontine and medullary reticular formation which project to the spinal cord through the ventrolateral funiculus [3, 7, 10, 20] play a role in the initiation of locomotion. Anatomical and electrophysiological evidence suggests that cells in the MLR project to reticulospinal neurons in these regions [12, Steeves and Jordan, unpublished observations]. Furthermore, stimulation in these same areas of the reticular formation can produce locomotion in post-mammillary cats [11]. Anatomical evidence indicates that cells in the region of the MLR do not project to the spinal cord (Steeves and Jordan, unpublished observation); thus, the initiation of locomotion by MLR stimulation may be via a pathway from the MLR to the pontine and medullary reticulospinal areas.
We thank Dr. E. Eidelberg and Dr. P.S.G. Stein for reading a draft of the manuscript, and Janet Greer for typing it. Supported by the Medical Research Council of Canada.
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