Recovery of locomotion in cats after severe contusion of the low thoracic spinal cord.

Large bilateral contusions of the T10 thoracic spinal cord were performed in 16 adult cats using a calibrated impactor. EMG and video recordings allowed weekly assessments of key locomotor parameters during treadmill training for 5 wk. Thirty-five days postcontusion, several hindlimb locomotor parameters were very similar to the prelesion ones despite some long-term deficits such as paw drag and disrupted fore-hindlimb coupling. Nine out of ten tested cats could step over obstacles placed on the treadmill. Acute electrophysiological experiments showed viable connectivity between segments rostral and caudal to the contusion. At the fifth postcontusion week, a complete spinalization was performed at T13 in 10 cats and all expressed remarkable bilateral hindlimb locomotion within 24-72 h. From our histological evaluation, we concluded that only a small percentage (~10%) of spinal cord pathways was necessary to initiate and maintain a voluntary quadrupedal locomotor pattern on a treadmill and even to negotiate obstacles. Our findings suggest that hindlimb stepping largely resulted from the activity of spinal locomotor circuits, which gradually recovered autonomy week after week. Our histological and electrophysiological evidence indicated that the persistence of specific deficits or else the maintenance of specific functions was related to the integrity of specific supraspinal and propriospinal pathways. The conclusion is that the recovery of locomotion after large spinal contusions depends on a homeostatic recalibration of a tripartite control system involving interactions between spinal circuits (central pattern generator), supraspinal influences, and sensory feedback activated through locomotor training.NEW & NOTEWORTHY The recovery of quadrupedal treadmill locomotion after a large bilateral contusion at the low thoracic T10 spinal level and the ability to negotiate obstacles were studied for 5 wk in 16 cats. Ten cats were further completely spinalized at T13 and were found to walk with the hindlimbs within 24-72 h. We conclude that the extent of locomotor recovery after large spinal contusions hinges both on remnant supraspinal pathways and on a spinal pattern generator.

Recovery of locomotion after spinal cord injury: some facts and mechanisms.

After spinal cord injury (SCI), various sensorimotor functions can recover, ranging from simple spinal reflexes to more elaborate motor patterns, such as locomotion. Locomotor recovery after complete spinalization (complete SCI) must depend on the presence of spinal circuitry capable of generating the complex sequential activation of various leg muscles. This is achieved by an intrinsic spinal circuitry, termed the central pattern generator (CPG), working in conjunction with sensory feedback from the legs. After SCI, different changes in cellular and circuit properties occur spontaneously and can be promoted by pharmacological, electrical, or rehabilitation strategies. After partial SCI, hindlimb locomotor recovery can result from regeneration or sprouting of spared pathways, but also from mechanisms observed after complete SCI, namely changes within the intrinsic spinal circuitry and sensory inputs.

Ladder Treadmill: A Method to Assess Locomotion in Cats with an Intact or Lesioned Spinal Cord.

After lesions of the CNS, locomotor abilities of animals (mainly cats) are often assessed on a simple flat treadmill (FTM), which imposes little demands on supraspinal structures as is the case when walking on targets. Therefore, the aims of the present work were as follows: (1) to develop a treadmill allowing the assessment of locomotion of intact cats required to place the paws on the rungs of a moving ladder treadmill (LTM); (2) to assess the capability of cats after a unilateral spinal hemisection at T10 to cope with such a demanding locomotor task; and (3) to regularly train cats for 6 weeks on the LTM to determine whether such regular training improves locomotor recovery on the FTM. A significant improvement would indicate that LTM training maximizes the contribution of spinal locomotor circuits as well as remnant supraspinal inputs. Together, we used 9 cats (7 females, 2 males). Six were used to compare the EMG and kinematic locomotor characteristics during walking on the FTM and LTM. We found that the swing phase during LTM walking was slightly enhanced as well as some specific activity of knee flexor muscles. Fore-hindlimb coupling favored a more stable diagonal coupling. These 6 cats were then hemispinalized and trained for 6 weeks on the LTM, whereas the 3 other cats were hemispinalized and trained solely on the FTM to compare the two training regimens. Intensive LTM training after hemisection was found to change features of locomotion, such as the foot trajectory as well as diminished paw drag often observed after hemisection.SIGNIFICANCE STATEMENT This paper introduces a method (ladder treadmill [LTM]) to study the locomotor ability of cats with an intact spinal cord or after a unilateral hemisection to walk with a precise foot placement on the rungs fixed to an ordinary flat treadmill (FTM). Because cats are compared in various conditions (intact or hemisected at different time points) in the same enclosure on the FTM and the LTM, the changes in averaged locomotor characteristics must reflect the specificity of the task and the neurological states. Furthermore, the ladder treadmill permits to train cats repetitively for weeks and observe whether training regimens (FTM or LTM) can induce durable changes in the parameters of locomotion.

Lower extremity outcome measures: considerations for clinical trials in spinal cord injury.

STUDY DESIGN: This is a focused review article. OBJECTIVES: To identify important concepts in lower extremity (LE) assessment with a focus on locomotor outcomes and provide guidance on how existing outcome measurement tools may be best used to assess experimental therapies in spinal cord injury (SCI). The emphasis lies on LE outcomes in individuals with complete and incomplete SCI in Phase II-III trials. METHODS: This review includes a summary of topics discussed during a workshop focusing on LE function in SCI, conceptual discussion of corresponding outcome measures and additional focused literature review. RESULTS: There are a number of sensitive, accurate, and responsive outcome tools measuring both quantitative and qualitative aspects of LE function. However, in trials with individuals with very acute injuries, a baseline assessment of the primary (or secondary) LE outcome measure is often not feasible. CONCLUSION: There is no single outcome measure to assess all individuals with SCI that can be used to monitor changes in LE function regardless of severity and level of injury. Surrogate markers have to be used to assess LE function in individuals with severe SCI. However, it is generally agreed that a direct measurement of the performance for an appropriate functional activity supersedes any surrogate marker. LE assessments have to be refined so they can be used across all time points after SCI, regardless of the level or severity of spinal injury. SPONSORS: Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Plastic Changes in Lumbar Locomotor Networks after a Partial Spinal Cord Injury in Cats.

After an incomplete spinal cord injury (SCI), we know that plastic reorganization occurs in supraspinal structures with residual descending tracts. However, our knowledge about spinal plasticity is rather limited. Our recent studies point to changes within the spinal cord below the lesion. After a lateral left hemisection (T10), cats recovered stepping with both hindlimbs within 3 weeks. After a complete section (T13) in these cats, bilateral stepping was seen on the next day, a skill usually acquired after several weeks of treadmill training. This indicates that durable plastic changes occurred below the lesion. However, because sensory feedback entrains the stepping rhythm, it is difficult to reveal central pattern generator (CPG) adaptation. Here, we investigated whether lumbar segments of cats with a chronic hemisection were able to generate fictive locomotion-that is, without phasic sensory feedback as monitored by five muscle nerves in each hindlimb. With a chronic left hemisection, the number of muscle nerves displaying locomotor bursts was larger on the left than on the right. In addition, transmission of cutaneous reflexes was relatively facilitated on the left. Later during the acute experiment, a complete spinalization (T13) was performed and clonidine was injected to induce rhythmic activities. There were still more muscle nerves displaying locomotor bursts on the left. The results demonstrate that spinal networks were indeed modified after a hemisection with a clear asymmetry between left and right in the capacity to generate locomotion. Plastic changes in CPG and reflex transmission below the lesion are thus involved in the stepping recovery after an incomplete SCI.

Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal cord section using repeated treadmill training with perineal stimulation only.

Although a complete thoracic spinal cord section in various mammals induces paralysis of voluntary movements, the spinal lumbosacral circuitry below the lesion retains its ability to generate hindlimb locomotion. This important capacity may contribute to the overall locomotor recovery after partial spinal cord injury (SCI). In rats, it is usually triggered by pharmacological and/or electrical stimulation of the cord while a robot sustains the animals in an upright posture. In the present study we daily trained a group of adult spinal (T7) rats to walk with the hindlimbs for 10 wk (10 min/day for 5 days/wk), using only perineal stimulation. Kinematic analysis and terminal electromyographic recordings revealed a strong effect of training on the reexpression of hindlimb locomotion. Indeed, trained animals gradually improved their locomotion while untrained animals worsened throughout the post-SCI period. Kinematic parameters such as averaged and instant swing phase velocity, step cycle variability, foot drag duration, off period duration, and relationship between the swing features returned to normal values only in trained animals. The present results clearly demonstrate that treadmill training alone, in a normal horizontal posture, elicited by noninvasive perineal stimulation is sufficient to induce a persistent hindlimb locomotor recovery without the need for more complex strategies. This provides a baseline level that should be clearly surpassed if additional locomotor-enabling procedures are added. Moreover, it has a clinical value since intrinsic spinal reorganization induced by training should contribute to improve locomotor recovery together with afferent feedback and supraspinal modifications in patients with incomplete SCI.

Emergence of deletions during treadmill locomotion as a function of supraspinal and sensory inputs.

During locomotion, alternating activity of flexor and extensor muscles is largely regulated by a spinal neuronal network, the central pattern generator, the activity of which is modulated by peripheral and supraspinal inputs. In the absence of these modulatory inputs, for example during fictive locomotion after spinalization and curarization, spontaneous failures of motor activation (deletions) in a muscle can occur without perturbing the rhythmic cycle structure of the antagonists on the same side or the contralateral side. This suggests that the central pattern generator can maintain the locomotor period when motoneuron discharges fail in a given pool of motoneurons. Here we first examined whether such deletions could occur during real locomotion on a treadmill and determined their consequences on the overt locomotor pattern. We also evaluated the role of supraspinal and sensory inputs in modulating the occurrence of failures of rhythmic activity by comparing the same cats in the intact state, then after a partial spinal cord injury (SCI), and finally after a complete SCI at different treadmill speeds. We showed that deletions: (1) are absent in intact animals and occur only after SCI; (2) affect only flexor muscle activity; (3) neither perturb the timing of rhythmic activity of these muscles in subsequent cycles nor interfere with the timing of the ipsilateral and contralateral agonists and antagonists; (4) do not affect significantly the locomotor pattern kinematics; and (5) are sensitive to treadmill speed and lesion severity, suggesting a role for sensory and supraspinal inputs in stabilizing rhythmic output activity.

Effect of locomotor training in completely spinalized cats previously submitted to a spinal hemisection.

After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

Treadmill training promotes spinal changes leading to locomotor recovery after partial spinal cord injury in cats.

After a spinal hemisection at thoracic level in cats, the paretic hindlimb progressively recovers locomotion without treadmill training but asymmetries between hindlimbs persist for several weeks and can be seen even after a further complete spinal transection at T13. To promote optimal locomotor recovery after hemisection, such asymmetrical changes need to be corrected. In the present study we determined if the locomotor deficits induced by a spinal hemisection can be corrected by locomotor training and, if so, whether the spinal stepping after the complete spinal cord transection is also more symmetrical. This would indicate that locomotor training in the hemisected period induces efficient changes in the spinal cord itself. Sixteen adult cats were first submitted to a spinal hemisection at T10. One group received 3 wk of treadmill training, whereas the second group did not. Detailed kinematic and electromyographic analyses showed that a 3-wk period of locomotor training was sufficient to improve the quality and symmetry of walking of the hindlimbs. Moreover, after the complete spinal lesion was performed, all the trained cats reexpressed bilateral and symmetrical hindlimb locomotion within 24 h. By contrast, the locomotor pattern of the untrained cats remained asymmetrical, and the hindlimb on the side of the hemisection was still deficient. This study highlights the beneficial role of locomotor training in facilitating bilateral and symmetrical functional plastic changes within the spinal circuitry and in promoting locomotor recovery after an incomplete spinal cord injury.

Incomplete spinal cord injury promotes durable functional changes within the spinal locomotor circuitry.

While walking in a straight path, changes in speed result mainly from adjustments in the duration of the stance phase while the swing phase remains relatively invariant, a basic feature of the spinal central pattern generator (CPG). To produce a broad range of locomotor behaviors, the CPG has to integrate modulatory inputs from the brain and the periphery and alter these swing/stance characteristics. In the present work we raise the issue as to whether the CPG can adapt or reorganize in response to a chronic change of supraspinal inputs, as is the case after spinal cord injury (SCI). Kinematic data obtained from six adult cats walking at different treadmill speeds were collected to calculate the cycle and subphase duration at different stages after a first spinal hemisection at T(10) and after a subsequent complete SCI at T(13) respectively aimed at disconnecting unilaterally and then totally the spinal cord from its supraspinal inputs. The results show, first, that the neural control of locomotion is flexible and responsive to a partial or total loss of supraspinal inputs. Second, we demonstrate that a hemisection induces durable plastic changes within the spinal locomotor circuitry below the lesion. In addition, this study gives new insights into the organization of the spinal CPG for locomotion such that phases of the step cycle (swing, stance) can be independently regulated for adapting to speed and also that the CPGs controlling the left and right hindlimbs can, up to a point, be regulated independently.

Recovery of hindlimb locomotion after incomplete spinal cord injury in the cat involves spontaneous compensatory changes within the spinal locomotor circuitry.

After incomplete spinal cord injury (SCI), compensatory changes occur throughout the whole neuraxis, including the spinal cord below the lesion, as suggested by previous experiments using a dual SCI paradigm. Indeed, cats submitted to a lateral spinal hemisection at T10-T11 and trained on a treadmill for 3-14 wk re-expressed bilateral hindlimb locomotion as soon as 24 h after spinalization, a process that normally takes 2-3 wk when a complete spinalization is performed without a prior hemisection. In this study, we wanted to ascertain whether similar effects could occur spontaneously without training between the two SCIs and within a short period of 3 wk in 11 cats. One day after the complete spinalization, 9 of the 11 cats were able to re-express hindlimb locomotion either bilaterally (n = 6) or unilaterally on the side of the previous hemisection (n = 3). In these 9 cats, the hindlimb on the side of the previous hemisection (left hindlimb) performed better than the right side in contrast to that observed during the hemispinal period itself. Cats re-expressing the best bilateral hindlimb locomotion after spinalization had the largest initial hemilesion and the most prominent locomotor deficits after this first SCI. These results provide evidence that 1) marked reorganization of the spinal locomotor circuitry can occur without specific locomotor training and within a short period of 3 wk; 2) the spinal cord can reorganize in a more or less symmetrical way; and 3) the ability to walk after spinalization depends on the degree of deficits and adaptation observed in the hemispinal period.

Dual spinal lesion paradigm in the cat: evolution of the kinematic locomotor pattern.

The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3-5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord.

Changes in spinal reflex excitability associated with motor sequence learning.

There is ample evidence that motor sequence learning is mediated by changes in brain activity. Yet the question of whether this form of learning elicits changes detectable at the spinal cord level has not been addressed. To date, studies in humans have revealed that spinal reflex activity may be altered during the acquisition of various motor skills, but a link between motor sequence learning and changes in spinal excitability has not been demonstrated. To address this issue, we studied the modulation of H-reflex amplitude evoked in the flexor carpi radialis muscle of 14 healthy individuals between blocks of movements that involved the implicit acquisition of a sequence versus other movements that did not require learning. Each participant performed the task in three conditions: "sequence"-externally triggered, repeating and sequential movements, "random"-similar movements, but performed in an arbitrary order, and "simple"- involving alternating movements in a left-right or up-down direction only. When controlling for background muscular activity, H-reflex amplitude was significantly more reduced in the sequence (43.8 +/- 1.47%. mean +/- SE) compared with the random (38.2 +/- 1.60%) and simple (31.5 +/- 1.82%) conditions, while the M-response was not different across conditions. Furthermore, H-reflex changes were observed from the beginning of the learning process up to when subjects reached asymptotic performance on the motor task. Changes also persisted for >60 s after motor activity ceased. Such findings suggest that the excitability in some spinal reflex circuits is altered during the implicit learning process of a new motor sequence.

Prominent role of the spinal central pattern generator in the recovery of locomotion after partial spinal cord injuries.

The re-expression of hindlimb locomotion after complete spinal cord injuries (SCIs) is caused by the presence of a spinal central pattern generator (CPG) for locomotion. After partial SCI, however, the role of this spinal CPG in the recovery of hindlimb locomotion in the cat remains mostly unknown. In the present work, we devised a dual-lesion paradigm to determine its possible contribution after partial SCI. After a partial section of the left thoracic segment T10 or T11, cats gradually recovered voluntary quadrupedal locomotion. Then, a complete transection was performed two to three segments more caudally (T13-L1) several weeks after the first partial lesion. Cats that received intensive treadmill training after the partial lesion expressed bilateral hindlimb locomotion within hours of the complete lesion. Untrained cats however showed asymmetrical hindlimb locomotion with the limb on the side of the partial lesion walking well before the other hindlimb. Thus, the complete spinalization revealed that the spinal CPG underwent plastic changes after the partial lesions, which were shaped by locomotor training. Over time, with further treadmill training, the asymmetry disappeared and a bilateral locomotion was reinstated. Therefore, although remnant intact descending pathways must contribute to voluntary goal-oriented locomotion after partial SCI, the recovery and re-expression of the hindlimb locomotor pattern mostly results from intrinsic changes below the lesion in the CPG and afferent inputs.

Asymmetric changes in cutaneous reflexes after a partial spinal lesion and retention following spinalization during locomotion in the cat.

Locomotion involves dynamic interactions between the spinal cord, supraspinal signals, and peripheral sensory inputs. After incomplete spinal cord injury (SCI), interactions are disrupted, and remnant structures must optimize function to maximize locomotion. We investigated if cutaneous reflexes are altered following a unilateral partial spinal lesion and whether changes are retained within spinal circuits after complete spinal transection (i.e., spinalization). Four cats were chronically implanted with recording and stimulating electrodes. Cutaneous reflexes were evoked with cuff electrodes placed around left and right superficial peroneal nerves. Control data, consisting of hindlimb kinematics and electromyography (bursts of muscular activity and cutaneous reflexes), were recorded during treadmill locomotion. After stable control data were achieved (53-67 days), a partial spinal lesion was made at the 10th or 11th thoracic segment (T(10)-T(11)) on the left side. Cats were trained to walk after the partial lesion, and following a recovery period (64-80 days), a spinalization was made at T(13). After the partial lesion, changes in short-latency excitatory (P1) homologous responses between hindlimbs, evoked during swing, were largely asymmetric in direction relative to control values, whereas changes in longer-latency excitatory (P2) and crossed responses were largely symmetric in direction. After spinalization, cats could display hindlimb locomotion within 1 day. Early after spinalization, reflex changes persisted a few days, but over time homologous P1 responses increased symmetrically toward or above control levels. Therefore changes in cutaneous reflexes after the partial lesion and retention following spinalization indicate an important spinal plasticity after incomplete SCI.

Plasticity of locomotor sensorimotor interactions after peripheral and/or spinal lesions.

The present paper reviews aspects of locomotor sensorimotor interactions by focussing on work performed in spinal cats. We provide a brief overview of spinal locomotion and describe the effects of various types of sensory deprivations (e.g. rhizotomies, and lesions of muscle and cutaneous nerves) to highlight the spinal neuroplasticity necessary for adapting to sensory loss. Recent work on plastic interactions between reflex pathways that could be responsible for such plasticity, in particular changes in proprioceptive and cutaneous pathways that occur during locomotor training of spinal cats, is discussed. Finally, we describe how stimulation of some sensory inputs via various limb manipulations or intraspinal electrical stimulation can affect the expression of spinal locomotion. We conclude that sensory inputs are critical not only for locomotion but also that changes in the efficacy of sensory transmission and in the interactions between sensory pathways could participate in the normalization of locomotion after spinal and/or peripheral lesions.

Spinal cord injury: time to move?

This symposium aims at summarizing some of the scientific bases for current or planned clinical trials in patients with spinal cord injury (SCI). It stems from the interactions of four researchers involved in basic and clinical research who presented their work at a dedicated Symposium of the Society for Neuroscience in San Diego. After SCI, primary and secondary damage occurs and several endogenous processes are triggered that may foster or hinder axonal reconnection from supralesional structures. Studies in animals show that some of these processes can be enhanced or decreased by exogenous interventions using drugs to diminish repulsive barriers (anti-Nogo, anti-Rho) that prevent regeneration and/or sprouting of axons. Cell grafts are also envisaged to enhance beneficial immunological mechanisms (autologous macrophages, vaccines) or remyelinate axons (oligodendrocytes derived from stem cells). Some of these treatments could be planned concurrently with neurosurgical approaches that are themselves beneficial to decrease secondary damage (e.g., decompression/reconstructive spinal surgery). Finally, rehabilitative approaches based on the presence of functional networks (i.e., central pattern generator) below the lesion combined with the above neurobiological approaches may produce significant functional recovery of some sensorimotor functions, such as locomotion, by ensuring an optimal function of endogenous spinal networks and establishing new dynamic interactions with supralesional structures. More work is needed on all fronts, but already the results offer great hope for functional recovery after SCI based on sound basic and clinical neuroscience research.

Adaptive changes of the locomotor pattern and cutaneous reflexes during locomotion studied in the same cats before and after spinalization.

Descending supraspinal inputs exert powerful influences on spinal reflex pathways in the legs. Removing these inputs by completely transecting the spinal cord changes the state (i.e. the configuration of the spinal circuitry) of the locomotor network and undoubtedly generates a reorganization of reflex pathways. To study changes in reflex pathways after a complete spinalization, we recorded spinal reflexes during locomotion before and after a complete transection of the spinal cord at the 13th thoracic segment in cats. We chronically implanted electrodes in three cats, to record electromyography (EMG) in several hindlimb muscles and around the left tibial (Tib) nerve at the ankle to elicit reflexes during locomotion before and after spinalization in the same cat. Control values of kinematics, EMGs and reflexes were obtained during intact locomotion for 33-60 days before spinalization. After spinalization, cats were trained 3-5 times a week on a motorized treadmill. Recordings resumed once a stable spinal locomotion was achieved (26-43 days), with consistent plantar foot placement and full hindquarter weight support without perineal stimulation. Changes in Tib nerve reflex responses after spinalization in the same cat during locomotion were found in all muscles studied and were often confined to specific phases of the step cycle. The most remarkable change was the appearance of short-latency excitatory responses in some ipsilateral ankle extensors during stance. Short-latency excitatory responses in the ipsilateral tibialis anterior were increased during stance, whereas in other flexors such as semitendinosus and sartorius, increases were mostly confined to swing. Longer-latency excitatory responses in ipsilateral flexors were absent or reduced. Responses evoked in limb muscles contralateral to stimulation were generally increased throughout the step cycle. These reflex changes after spinalization provide important clues regarding the functional reorganization of reflex pathways during spinal locomotion.

Cineradiographic (video X-ray) analysis of skilled reaching in a single pellet reaching task provides insight into relative contribution of body, head, oral, and forelimb movement in rats.

The forelimb movements (skilled reaching) used by rats to reach for a single food pellet to place into the mouth have been used to model many neurological conditions. They have been described as a sequence of oppositions of head-pellet, paw-pellet and pellet-mouth that can be described as movements of the distal portion of body segments in relation to their fixed proximal joints. Movement scoring is difficult, however, because the location and movement of body segments is estimated through the overlying fur and skin, which is pliable and partially obscures movement. Using moderately high-speed cineradiographic filming from lateral, dorsal, and frontal perspectives, the present study describes how forelimb and skeletal bones move during the skilled reaching act. The analysis indicates that: (i) head movements for orienting to food, enabled by the vertical orientation of the rostral spinal cord, are mainly independent of trunk movement, (ii) skilled reaching consists of a sequence of upper arm and extremity movements each involving a number of concurrent limb segment and joint movements and (iii) food pellets are retrieved from the paw using either the incisors and/or tongue. The findings are discussed in relation to the idea that X-ray cinematography is valuable tool for assisting descriptive analysis and can contribute to understanding general principles of the relations between whole body, head, oral, and upper extremity movement.

Axon and Myelin Morphology in Animal and Human Spinal Cord.

Characterizing precisely the microstructure of axons, their density, size and myelination is of interest for the neuroscientific community, for example to help maximize the outcome of studies on white matter (WM) pathologies of the spinal cord (SC). The existence of a comprehensive and structured database of axonal measurements in healthy and disease models could help the validation of results obtained by different researchers. The purpose of this article is to provide such a database of healthy SC WM, to discuss the potential sources of variability and to suggest avenues for robust and accurate quantification of axon morphometry based on novel acquisition and processing techniques. The article is organized in three sections. The first section reviews morphometric results across species according to range of densities and counts of myelinated axons, axon diameter and myelin thickness, and characteristics of unmyelinated axons in different regions. The second section discusses the sources of variability across studies, such as age, sex, spinal pathways, spinal levels, statistical power and terminology in regard to tracts and protocols. The third section presents new techniques and perspectives that could benefit histology studies. For example, coherent anti-stokes Raman spectroscopy (CARS) imaging can provide sub-micrometric resolution without the need for fixation and staining, while slide scanners and stitching algorithms can provide full cross-sectional area of SC. In combination with these acquisition techniques, automatic segmentation algorithms for delineating axons and myelin sheath can help provide large-scale statistics on axon morphometry.