Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat

Identification of long tracts responsible for spontaneous locomotion is critical for spinal cord injury (SCI) repair strategies. We recently demonstrated that extensive demyelination of adult rat thoracic ventral columns, ventromedial, and ventrolateral white matter produces persistent, significant open-field hindlimb locomotor deficits. Locomotor movements resulting from stimulation of the pontomedullary locomotor region are inhibited by dorsolateral funiculus (DLF) lesions suggesting that important pathways for locomotion may also exist in the dorsal white matter. However, dorsal hemisections that interrupt dorsal columns/dorsal corticospinal tract (DC/CST) and DLF pathways do not produce persistent, severe locomotor deficits in the adult rat. We studied the contributions of myelinated tracts in the DLF and DC/CST to overground locomotion following complete conduction blockade of axons in the ventrolateral funiculus (VLF), a region important for locomotor movements and for transcranial magnetic motor-evoked potentials (tcMMEP). Animals received ethidium bromide plus photon irradiation to produce discrete demyelinating lesions sufficient to stop axonal conduction in the VLF, combined VLF + DLF, or combined VLF + DC/CST. Open-field BBB scores and tcMMEPs were studied at 1, 2, 3, and 4 weeks postlesion. VLF lesions resulted in mean BBB scores of 17 at 4 weeks. VLF + DC/CST and VLF + DLF lesions resulted in mean BBB scores of 15.9 and 11.1, respectively. TcMMEPs were absent in all lesion types confirming VLF conduction blockade throughout the study. Our data indicate that significant contributions to locomotion from myelinated pathways within the rat DLF can be revealed when combined with simultaneous compromise of the VLF.     

Effects of combined dorsolateral and dorsal funicular lesions on sensorimotor behaviour in rats

The purpose of this research was to investigate the compensatory role of undamaged spinal pathways after partial spinal injury in rats. We have previously shown that bilateral lesions of the dorsal funiculus (DF) at the cervical level caused changes in overground and skilled locomotion that affected the forelimbs more than the hindlimbs. The same lesions also caused fore-paw deficits during a skilled pellet retrieval task (Kanagal and Muir, 2007). In contrast, bilateral cervical lesions of the dorsolateral funiculus (DLF) caused alterations in overground and skilled locomotion that were most marked in the hindlimbs rather than the forelimbs, but also caused fore-paw deficits during skilled pellet retrieval (Muir et al., 2007). We hypothesized that the relative lack of forelimb deficits during locomotion after DLF lesions was due to compensatory input arising from intact pathways in the DF. We tested this hypothesis in the present study by performing bilateral DF lesions in animals in which both DLFs had been transected 6 weeks previously. These secondary DF lesions involved either only ascending sensory pathways (DLF+ASP group) in the DF, i.e. sparing the corticospinal tract (CST), or involved both the ASP and the CST (DLF+DF group). All animals were assessed during overground locomotion, while crossing a horizontal ladder and during a pellet retrieval task. During overground locomotion, both groups moved with slightly altered forces and timing in both forelimbs and hindlimbs. During both ladder crossing and reaching, secondary lesions to DF (with or without CST) exacerbated the deficits seen after initial DLF lesions and additionally caused changes in the manner in which the rats used their forelimbs during reaching. Nevertheless, the relative magnitude of the deficits indicates that DF pathways in rats likely do not compensate for loss of DLF pathways during the execution of locomotor tasks, though there is indirect evidence that DLF-lesioned rats might rely more on ascending sensory pathways in the DF during skilled forelimb movements. The plastic changes mediating recovery are therefore necessarily occurring in other regions of the CNS, and, importantly, need time to develop, because animals with DLF+DF lesions performed simultaneously displayed marked functional deficits and were unable to use their forelimbs for skilled locomotion or reaching.     

Coordination of movements of the kindlimbs and forelimbs in different forms of locomotion in normal and decerebrate cats.

The coupling of movements of the hindlimbs and forelimbs has been analysed in intact cats stepping overground and on a treadmill and during swimming, and in decerebrate cats stepping on a treadmill, immersed in water('swimming') and stepping suspended in the air. In the different preparations, and under different types of locomotion, two basic patterns of coupling have been observed. Both concern the hindlimb and forelimb of the same side of the body. The first pattern is found in the pacing gait where flexion of the forelimb precedes extension of the hindlimb, measured at the elbow and knee, respectively. The second pattern is typically found in the trot where flexion of the forelimb follows extension of the hindlimb. In decerebrate cats both patterns of coupling remain after bilateral deafferentation of the hindlimbs. In the alternate form of locomotion these patterns of coupling occurs symmetrically on both sides. In the rotatory and transverse gallop (examples of the in-phase form of locomotion) the coupling is asymmetrical: on one side it is comparable to pacing (forelimb flexion precedes hindlimb extension), and on the other side to trotting (forelimb flexion follows extension). These basic patterns of interlimb coordination simplify considerably the problem of neural control of the limbs in locomotion. Obersations of EMGs during the alternative forms of locomotion show that in the pacing type of coupling the extensor EMGs of forelimb and hindlimb overlap, with the hindlimb leading the forelimb by about 10% of a step cycle, while in the trotting type of coupling the forelimb flexor EMGs overlap the hindlimb extensor EMGs, the forelimb flexors leading the hindlimb extensors by about 10% of a step cycle. During acceleration the transition between the two forms of EMG occurs within one or two step cycles, and at some intermediate velocities the EMG coupling springs back and forth between the two different forms. These results further support the hypotesis of two basic forms of interlimb coupling in which long propriospinal pathways probably play a role.     

Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions in rats

The purpose of this research was to investigate whether pathways in the dorsal part of the lateral spinal funiculus (DLF) can compensate for loss of corticospinal input (CST) to the spinal cord. The CST is known to control skilled limb movements in rats. The DLF contains several different pathways, including the rubrospinal tract (RST) which is also thought to influence limb movements. After lesions of either the corticospinal or the rubrospinal system, it is unclear how much of the remaining forelimb function is due to the presence of the alternate pathway. To begin to address this issue, the present study investigates the compensatory role of pathways in the DLF, including the rubrospinal tract, after bilateral lesions of the pyramidal tract (PT). We initially performed bilateral PT lesions in rats, which effectively removed the CST input to the spinal cord. We tested these rats during overground locomotion, skilled locomotion and skilled forelimb usage. After a 6 week recovery period, we then performed bilateral DLF lesions and compared the behavioural abilities of these rats to those of animals which underwent simultaneous PT and DLF lesions. If DLF pathways do compensate for PT lesions, then animals with PT lesions would rely more on DLF pathways than animals without PT lesions. Thus we hypothesized that animals with DLF lesions which were performed 6 weeks after PT lesions would exhibit more deficits on several behavioural tasks compared to animals which received PT and DLF lesions simultaneously. Our hypothesis was supported only for skilled pellet retrieval. Hence some DLF pathways, including the RST, were able to compensate for loss of CST input during skilled reaching but not during overground or skilled locomotion in PT-lesioned rats. These differential responses suggest that behavioural tasks vary in their reliance on specific pathways after injury, and, furthermore, that compensation for loss of specific connections can arise from numerous sources.     

Funicular organization of avian brainstem-spinal projections.

The purpose of this study was to determine which reticulospinal projections need to be preserved to allow voluntary walking and to differentiate between those pathways descending within the ventrolateral funiculus versus the ventromedial funiculus. Retrogradely transported tracers (True Blue, Fast Blue, Diamidino Yellow dihydrochloride, fluorescein-conjugated dextran-amines) were used alone as discrete funicular injections (4-5 microliters) into the lumbar cord (L1), or in conjunction with a more rostral subtotal lesion of the low thoracic cord, to determine the trajectories of brainstem-spinal projections in adult ducks and geese. No difference was found between the species. The major components of the ventromedial funiculus include projections from the medullary reticular formation, pontine reticular formation, raphe obscurus and pallidus, lateral vestibular nucleus, and interstitial nucleus, and to a minor extent from the locus coeruleus, lateral hypothalamus, and nucleus periventricularis hypothalami. The components of the ventrolateral funiculus (VLF) include projections from the nucleus of the solitary tract, nucleus alatus, pontomedullary reticular formation, raphe pallidus, raphe magnus, locus coeruleus, subcoeruleus, lateral vestibular, and descending vestibular nuclei. The principal descending projections within the dorsolateral funiculus (DLF) arose from the red nucleus, the paraventricular nucleus, locus coeruleus, subcoeruleus, dorsal division of the caudal medullary reticular formation, and raphe magnus. The functional implications of the distribution of these descending pathways are discussed with regard to locomotion. Since birds were able to walk despite bilateral lesion of the DLF or VMF but were unable to walk following a bilateral lesion of the VLF, this suggests that medullary reticulospinal pathways coursing within the VLF are essential for the provision of locomotor drive.     

Comparison between ventral spinocerebellar and rubrospinal activities during locomotion in the cat

During fictive locomotion of the thalamic cat, rhythmic activity related to the efferent discharges in hindlimb nerves was found in rubrospinal neurons (Arshavsky et al., this issue). Since the movements were abolished by curarization, this modulation could not result from rhythmic peripheral inputs and had therefore a central origin. Taking into account the existence of spinal generators, it was suggested that ascending pathways transmit rhythmic activity from these spinal centers to the supraspinal ones. Preliminary results have been obtained for neurons of the ventral spinocerebellar tract (VSCT) recorded during fictive locomotion: (1) their discharge is rhythmically modulated at the periodicity of the locomotor rhythm; (2) their discharge pattern can be complex and variable in relation with the complexity and variability of the pattern of efferent activity in various muscle nerves of the ipsilateral hindlimb; (3) their responses to phasic afferent stimulation of the ipsilateral hindlimb are modulated in parallel with their locomotor-related activity. These results show that VSCT neurons convey information on the central spinal activity during locomotion, and suggest that these neurons contribute to the activity of lumbar-projecting rubrospinal neurons which have similar characteristics.     

Dorsolateral cervical spinal injury differentially affects forelimb and hindlimb action in rats

In experimental spinal injury studies, damage to the dorsal half of the spinal cord is common but the behavioural effects of damage to specific pathways in the dorsal cord have been less well investigated. We performed bilateral transection of the dorsolateral spinal funiculus (DLF) on 12 Long-Evans rats at the third cervical spinal segment. We quantified overground locomotion by measuring ground reaction forces, step timing and step distances as animals moved unrestrained. We also assessed skilled locomotion by measuring footslip errors made while the animals crossed horizontal ladders, and examined paw usage in a cylinder exploration task and during a skilled reaching task. Ground reaction forces revealed that rats with bilateral DLF lesions moved with a symmetrical gait, characterized mainly by altered forces exerted by the hindlimbs, delayed onset of hindlimb stance, and understepping of the hindlimbs relative to the forelimbs. These alterations in overground locomotion were subtle but were nevertheless consistent between animals and persisted throughout the 6-week recovery period. During ladder crossing, rats with DLF lesions made more footslip errors with the hindlimbs after surgery than before. Spontaneous forelimb usage during exploration was not affected by DLF axotomy but lesioned animals were less successful during skilled reaching. This is the first study which describes preferentially altered hindlimb use during overground locomotion after cervical DLF transections. We discuss these findings in relation to previous work and to the possible contributions of different ascending and descending pathways in the DLF to locomotion and skilled movements in rats.     

Role of joint afferents in relation to the initiation of forelimb stepping in thalamic cats

To analyze the roles of joint afferents in relation to initiation of forelimb stepping in thalamic cats, we recorded the unit spikes of the cervical dorsal roots, stimulated the joint afferents, and applied local anesthesia to the joint capsule. Almost all of the joint afferents of the shoulder, elbow, wrist and finger adapted slowly and exhibited alternating firing during forelimb stepping. About 45% of the afferents of each joint showed firings as the limb moved from forward to backward. About 44% of the afferents exhibited discharges as the limb moved from backward to forward. The remaining afferents showed firings as the limb moved in both directions. The application of local anesthesia to joints of the shoulder, elbow or wrist resulted in a marked reduction of forelimb stepping. Forelimb stepping was evoked by electric stimulation of the joint capsule, when excitabilities of flexor motoneurons were increased due to muscle stretching. Impulses originating in the joint afferents of the forelimb entered the spinal cord and ascended to the dorsolateral funiculus of the cervical cord, since forelimb stepping was abolished after bilateral transection of this part. Our results indicate that joint afferents may play an important role in the initiation of forelimb stepping in thalamic cats walking on a motor-driven treadmill.     

Stimulus time-locked responses of motoneurons during forelimb fictive locomotion evoked by repetitive stimulation of the lateral funiculus

In cat forelimb fictive locomotion evoked by repetitive stimulation of the upper cervical lateral funiculus, locomotor discharges consisted of activities time-locked to each stimulus, which were rhythmically modulated. The stimulus time-locked activities were investigated by intracellular recording from motoneurons. In both elbow flexor and extensor motoneurons, there observed stimulus time-locked disynaptic EPSPs, trisynaptic IPSPs and polysynaptic EPSPs, all of which were rhythmically modulated with specific patterns. The disynaptic EPSPs of flexor motoneurons were facilitated in the flexor phase of locomotion, whereas those of extensor motoneurons were facilitated from the flexor phase to the flexor-to-extensor transition phase. Modulation depth was larger in flexor motoneurons. Trisynaptic IPSPs changed in amplitude in parallel with the disynaptic EPSPs of the antagonistic motoneurons. Late, polysynaptic EPSPs of both flexor and extensor motoneurons increased in amplitude along with corresponding nerve discharges. After lesions of the lateral funiculus at C6/C7, both the disynaptic EPSPs and trisynaptic IPSPs were abolished in the motoneurons located caudally to the lesions. However, only trisynaptic IPSPs were lost in the rostrally located motoneurons. Furthermore, the lesions disclosed that extensor motoneurons received another kind of stimulus time-locked EPSPs, trisynaptic EPSPs, which were transmitted through the ventral part of the spinal cord, and rhythmically facilitated in the extensor phase. Stimulus time-locked PSPs observed in this study may at least in part be evoked by last-order interneurons of the central pattern generator, which may be reciprocally organized.     

Phase-dependent modulation of primary afferent depolarization in single cutaneous primary afferents evoked by peripheral stimulation during fictive locomotion in the cat

Previous results from our laboratory have shown with intra-axonal recordings that hindfoot cutaneous primary afferents are subjected to rhythmic depolarizations during fictive locomotion (L-PAD) suggesting that cutaneous presynaptic mechanisms are activated by the central locomotor program. In this study, we examined the transmission in pathways responsible for primary afferent depolarizations (PAD) of cutaneous fibres during spontaneous fictive locomotion in decorticate cats and in spinal cats injected with nialamide and L-DOPA. PADs were evoked (E-PADs) by electrical stimulation of peripheral nerves and recorded intra-axonally with micropipettes in identified superficialis peroneal (SP; n = 7) and tibialis posterior (TP; n = 17) cutaneous primary afferents. Results showed that the amplitude of E-PADs, which were superimposed on the L-PAD, was deeply modulated throughout the locomotor cycle; decreasing to reach a minimum during the flexor phase and increasing to a maximum during the extensor phase. The results were not statistically different in fibres of the two nerves and in both types of preparation. The amplitude of E-PADs was always maximum during the extensor phase whether there was a large L-PAD or not during that phase. This suggests that the presynaptic mechanisms activated by central locomotor networks (L-PAD) and those activated by peripheral inputs (E-PAD) may in part be controlled differently. The results thus show that the transmission in PAD pathways activated by cutaneous inputs is phasically modulated by the central pattern generator for locomotion. This strongly suggests that the presynaptic inhibition in cutaneous fibres evoked by the movement-related feedback during real locomotion could be similarly modulated.     

Activity of propriospinal neurons of segments C3 and C4 during "fictive locomotion" in the cat

The activity of C3-C4 propriospinal neurons was recorded during "fictitious locomotion" of forelimbs in immobilized decerebrated cats with the spinal cord transected at the lower thoracal level. The neurons were identified by the antidromic responses to stimulation of the lateral funiculus in the C6 segment. Most of the neurons (70%) were antidromically activated also from the lateral reticular nucleus. The discharge frequency of most neurons was rhythmically modulated in correlation with the motoneuron activity during "fictitious locomotion", i.e. in the absence of any rhythmical signals from the limb receptors. The cooling of the rostral area of the cervical enlargement abolished both the generation of the locomotor rhythm and the rhythmical activity of the propriospinal neurons. Therefore intraspinal mechanisms controlling the forelimb activity are the main source for rhythmical modulation of the C3-C4 propriospinal neurons.     

The effect of selective brainstem or spinal cord lesions on treadmill locomotion evoked by stimulation of the mesencephalic or pontomedullary locomotor regions

The descending pathways from the brainstem locomotor areas were investigated by utilizing reversible cooling (to block synaptic or fiber transmission) and irreversible subtotal lesions of the brainstem or spinal cord (C2-C3 level). Experiments were conducted on decerebrate cats induced to walk on a treadmill by electrical stimulation of the brainstem. Locomotion produced by stimulation of the mesencephalic locomotor region (MLR) was not abolished by caudal brainstem lesions that isolated the lateral tegmentum or by extended rostral/caudal dorsal hemisections of the spinal cord. These results demonstrate that the MLR does not require a pathway projecting through the lateral tegmentum of the brainstem or the dorsal half of the spinal cord, as previously suggested (Mori et al., 1977, 1978b; Shik and Yagodnitsyn, 1978; Shik, 1983). Rather, the results indicate that the descending pathway originating from the MLR projects through the medial reticular formation (MedRF) and the ventral half of the spinal cord. Locomotion produced by stimulation of the pontomedullary locomotor region (PLR) was blocked by reversible cooling of either the MedRF or the ventrolateral funiculus of the spinal cord. In some cases, locomotion could be produced by stimulation of the PLR following extended dorsal hemisections of the spinal cord. These results demonstrate that the PLR can also produce locomotion by activation of cells in the MedRF that project caudally through the ventral half of the spinal cord. Stimulation of the PLR could also elicit locomotion following its surgical isolation from the MedRF of the brainstem. Furthermore, lesions of the dorsal spinal cord resulted in the loss of PLR-evoked locomotion in some, but not all, cases. Thus, an alternative projection of the PLR through the dorsal half of the spinal cord (Kazennikov et al., 1980, 1983a,b; Shik, 1983) cannot be ruled out. Overall, these results demonstrate that the PLR is not an essential component of the motor pathway originating from the MLR. The organizational scheme of "brainstem locomotor regions" is discussed in the context of recent information demonstrating a link between the sensory component of the trigeminal system and locomotor pathways (Noga et al., 1988).     

Phase-dependent modulation of dorsal root potentials evoked by peripheral nerve stimulation during fictive locomotion in the cat

To help elucidate the role of presynaptic mechanisms in the control of locomotor movements, the transmission of PAD pathways was investigated by recording dorsal root potentials (DRPs) evoked by electrical stimulation of cutaneous and muscle nerves of both hindlimbs at various phases of the fictive step cycle. Fictive locomotion occurred spontaneously in decorticate cats or by stimulating the mesencephalic locomotor region (MLR) as well as in low spinal cats injected with nialamide and L-DOPA. Evoked DRPs were superimposed on a fluctuating DRP accompanying the fictive locomotor rhythm (locomotor DRP) which typically consisted of two peaks of depolarization per cycle, the largest peak occurring during the flexor phase. The amplitude of evoked DRPs was substantially modulated throughout the locomotor cycle and followed a similar modulation pattern for all stimulated nerves whether ipsilateral (i-) or contralateral (co-). The amplitude of evoked DRPs decreased at the beginning of the flexor phase, dropped to a minimum later in the flexor phase and then increased during the extensor phase where it became maximum. Results were comparable in decorticate and spinal preparations and for L6 and L7 rootlets with cutaneous and muscle nerve stimulation. It is noteworthy that the modulation pattern for a given rootlet was similar for i- and co- stimulation, even though the bilateral locomotor DRPs fluctuate out-of-phase with each other, subjecting the stimulated fibres to opposite presynaptic polarization changes. This suggests that the modulation may depend more on the presynaptic mechanisms of the receiving fibres than on those of the stimulated fibres. These results demonstrate that the transmission in spinal pathways involved in primary afferent depolarization (PAD) is phasically modulated by the activity in the spinal locomotor network. It is further suggested that the presynaptic inhibition associated with PAD evoked by movement-related sensory feedback during real locomotion could be modulated in a similar way.     

Anatomical correlates of locomotor recovery following dorsal and ventral lesions of the rat spinal cord

The present study was designed to relate functional locomotor outcome to the anatomical extent and localization of lesions in the rat spinal cord. We performed dorsal and ventral lesions of different severity in 36 adult rats. Lesion depth, spared total white matter, and spared ventrolateral funiculus were compared to the locomotor outcome, assessed by the BBB open-field locomotor score and the grid walk test. The results showed that the preservation of a small number of fibers in the ventral or lateral funiculus was related to stepping abilities and overground locomotion, whereas comparable tissue preservation in the dorsal funiculus resulted in complete paraplegia. The strongest relation to locomotor function was between the BBB score and the lesion depth as well as the BBB score and the spared white matter tissue in the region of the reticulospinal tract. Locomotion on the grid walk required sparing in the ventrolateral funiculus and additional sparing of the dorsolateral and dorsal funiculus, where the cortico- and rubrospinal tracts are located.     

Modulation of reflex responses during fictive locomotion in the forelimb of the cat

During cat forelimb fictive locomotion, short-latency reflex pathways were examined by recording nerve discharges and intracellularly from motoneurones. Stimulation of cutaneous afferents, superficial radial nerves, evoked trisynaptic excitation of the elbow flexors, biceps brachii and brachialis, and stimulation of muscle afferents, deep radial nerves, evoked oligosynaptic, i.e. monosynaptic and disynaptic excitation of the flexors. The short-latency excitatory postsynaptic potentials (EPSPs) evoked from both nerves were rhythmically modulated; they were facilitated during the flexion phase and suppressed during the extension phase. Stimulation of high threshold muscle afferents evoked EPSPs with a central delay of ca. 4.2 ms, which were depressed throughout episodes of fictive locomotion. Since the short-latency EPSPs and longer-latency EPSPs in the same motoneurone were differently influenced during fictive locomotion, the effects observed could not be explained by changes occurring at only the motoneuronal level but they probably occurred at the premotoneuronal level. In addition, short-latency cutaneous excitation of the distal muscles, innervated by the median and ulnar nerves, was little modulated during fictive locomotion.     

Mapping the Dynamic Recruitment of Spinal Neurons during Fictive Locomotion

The basic rhythmic activity that underlies stepping is generated by a neural network, situated in the spinal cord, known as the locomotor central pattern generator (CPG). While a series of lesion experiments have demonstrated that the mammalian locomotor CPG is distributed throughout the ventral portion of the caudal spinal cord, the specific transverse distribution of this neural network is unclear. Here we evoke fictive locomotor activity of various frequencies in upright spinal cords prepared from male and female neonatal mice. This preparation enables us to use an imaging approach to identify locomotor-related cells across the transverse plane of the spinal cord. Results indicate that there is a clear shift in the recruitment of cells toward the ventromedial, and away from the ventrolateral, spinal cord as the frequency of fictive locomotion increases. Surprisingly, the analysis of multiple frequencies of fictive locomotion in the same spinal cord indicates that few neurons are involved in locomotor outputs across multiple speeds. Collectively, these experiments allow us to map the transverse distribution of the locomotor CPG and highlight the pattern of dynamic recruitment that occurs within this neural circuit as the frequency is altered. Our findings are consistent with data indicating that there is a speed-dependent recruitment of interneuronal populations during locomotion and suggest that the locomotor CPG is not a static network, but rather the specific cells recruited vary extensively based on demand.SIGNIFICANCE STATEMENT In this article, we use an imaging approach to identify all those cells that are rhythmically active at the same frequency as fictive locomotion recorded from the ventral roots of the isolated spinal cord. These experiments allow us to map the distribution of locomotor-related cells across the transverse plane of the spinal cord and identify the recruitment pattern of these cells as the frequency of locomotor outputs is altered. Our results indicate that there are drastic changes in the specific neurons activated at different frequencies and provide support for the concept that the locomotor central pattern generator is a modular network with speed-dependent recruitment of interneuronal components.     

Locomotor sites mapped with low current stimulation in intact and kainic acid damaged hypothalamus of anesthetized rats.

To determine whether local neurons mediated the locomotor effects of electrical stimulation of the lateral hypothalamus, kainic acid injections (0.5-1.25 micrograms), intended to destroy neural somata as opposed to fibers of passage, were made unilaterally in the tuberal-posterior hypothalamus of 22 rats. The area of lesion and its contralateral homolog were mapped for locomotor stepping sites in Nembutal-anesthetized rats mounted in a stereotaxic apparatus such that locomotor stepping rotated a wheel. Stimulation (25 and 50 microA, 50 Hz, 0.5-ms cathodal pulses, 10-s trains) was delivered through 50-80 microns glass pipettes filled with 2 M saline. Contralateral to the lesion, locomotor stepping sites were common in the perifornical lateral and medial hypothalamus and less dense in the zona incerta. On the side of the kainic-acid lesion, locomotor sites were generally absent in the central part of the damaged area. If they did appear within the area of lesion, they tended to be near the border with intact tissue. In a few cases, locomotor stepping sites were found centrally located in the lesion amidst widespread loss of somata. In four rats, additional maps of anterior locomotor regions in the preoptic area ipsilateral to the lesion suggested that their descending fibers were largely spared by the kainic lesions. Local neurons appear to be major contributors to the locomotion elicited by electrical stimulation of the lateral hypothalamus, but fibers of passage may also participate.     

The differential effects of cervical and thoracic dorsal funiculus lesions in rats

The purpose of this research was to compare the locomotor abilities of rats with cervical dorsal spinal funicular (DF) lesions to those of rats with the same lesion at the mid-thoracic level. The dorsal funiculus, consisting of ascending sensory fibers and the main component of the corticospinal tract, was transected either at spinal level C2 or at T8. We examined limb force generation and limb timing and coordination during overground locomotion, as well as foot placement errors during locomotion over a horizontal ladder. At 6 weeks post-surgery, bilateral lesions of the cervical DF caused subtle but persistent changes in the generation of ground reaction forces and limb timing during overground locomotion, and caused persistent forelimb, but not hindlimb, errors during ladder crossing. In contrast, the same lesion at the mid-thoracic level did not affect overground locomotion and caused only minor forelimb and hindlimb errors during ladder walking at 2 weeks post-lesion which recovered to pre-surgical levels by 6 weeks post-lesion. DF lesions at cervical vs. thoracic levels thus have differential effects on locomotor abilities in rats. We compare these results with previous work and suggest that the differential response to DF transection might be related to both functional distinctions between the fore- and hindlimbs and to anatomical differences in the dorsal funiculi at different spinal levels. These findings have implications for the mechanisms of recovery as well as the types of behavioural tests which can be practically used to measure functional changes in different lesion models.     

The effect of 4-aminopyridine on the spinal locomotor rhythm induced byl-DOPA

In high spinal curarized cats rhythmic motor output similar to locomotion (‘fictive locomotion’) of all 4 limbs was obtained after intravenous application of the noradrenergic precursor,l-DOPA, and nialamide combined with 4-aminopyridine (4-AP). The activity was recorded from muscle nerves.In the presence of 4-AP, which enhances transmission at various excitatory and inhibitory synapses, reduced amounts of DOPA were sufficient to evole fictive locomotion. 4-AP alone did not elicit locomotion.The burst rate increased up to 6 Hz with the amount of 4-AP given (0.5–50 mg/kg).The cycle frequency of high spinal cats exhibiting either fictive locomotion or walking on a treadmill was accelerated by 4-AP.After a supplementary transection of the spinal cord at the upper lumbar level both fore- and hindlimbs generally continued to show fictive locomotion with similar frequencies.In the presence of high doses of clonidine (alpha-receptor-activator, > 4mg/kg), the locomotor pattern was replaced by regular (2 Hz) synchronous discharges in all flexors and extensors.     

The synaptic responses of the neurons in the medulla oblongata to stimulation of the stepping stria of the spinal cord in the cat

Synaptic responses of bulbar neurons to stimulation of stepping points in the dorsolateral funiculus were recorded in decerebrate cats. 40% of neurons were excited from both ipsi- and contralateral stepping points, the rest of them were excited only from one of those points. Part of the neurons was activated from stepping points at both C2 and Th12 spinal cord levels. Latencies of the synaptic responses to stimulation of the stepping point at the cervical level were from 2 to 18 ms. These results suggest that bulbar neurons as well as propriospinal ones contribute to initiation of locomotion.