Adaptive mechanisms of spinal locomotion in cats

This paper reviews some aspects of locomotor plasticity afterspinalisation and after peripheral nerve lesions. Adult catscan recover spontaneous hindlimb locomotion on a treadmill severaldays or weeks after a complete section of the spinal cord atT13. The kinematics as well as the electromyographic activityare compared in the same animal before and after the spinalsection to highlight the resemblance of locomotor characteristicsin the two conditions. To study further the mechanisms of spinalplasticity potentially underlying such locomotor recovery, wealso summarize the locomotor adaptation of cats submitted tovarious types of peripheral nerve section of either ankle flexoror extensor muscles or after denervation of the hindpaws' cutaneousinputs. It is argued that, even in the spinal state, cats havethe ability to compensate for such lesions of the peripheralnervous system suggesting that the spinal cord has a significantpotential for adaptive plasticity that could be used in rehabilitationstrategies to restore locomotion after spinal cord injury.     

Plasticity of connections underlying locomotor recovery after central and/or peripheral lesions in the adult mammals

This review discusses some aspects of plasticity of connections after spinal injury in adult animal models as a basis for functional recovery of locomotion. After reviewing some pitfalls that must be avoided when claiming functional recovery and the importance of a conceptual framework for the control of locomotion, locomotor recovery after spinal lesions, mainly in cats, is summarized. It is concluded that recovery is partly due to plastic changes within the existing spinal locomotor networks. Locomotor training appears to change the excitability of simple reflex pathways as well as more complex circuitry. The spinal cord possesses an intrinsic capacity to adapt to lesions of central tracts or peripheral nerves but, as a rule, adaptation to lesions entails changes at both spinal and supraspinal levels. A brief summary of the spinal capacity of the rat, mouse and human to express spinal locomotor patterns is given, indicating that the concepts derived mainly from work in the cat extend to other adult mammals. It is hoped that some of the issues presented will help to evaluate how plasticity of existing connections may combine with and potentiate treatments designed to promote regeneration to optimize remaining motor functions.     

Locomotion induced by epidural stimulation in a decerebrated cat after spinal cord injury

The effect of partial and complete spinal cord transection (Th7–Th8) on locomotor activity evoked in decerebrated cats by electrical epidural stimulation (segment L5, 80–100 μA, 0.5 ms at 5 Hz) has been investigated. Transection of dorsal columns did not substantially influence the locomotion. Disruption of the ventral spinal quadrant resulted in deterioration and instability of the locomotor rhythm. Injury to lateral or medial descending motor systems led to redistribution of the tone in antagonist muscles. Locomotion could be evoked by epidural stimulation within 20 h after complete transection of the spinal cord. The restoration of polysynaptic components in EMG responses correlated with recovery of the stepping function. The data obtained confirm that initiation of locomotion under epidural stimulation is caused by direct action on intraspinal systems responsible for locomotor regulation. With intact or partially injured spinal cord, this effect is under the influence of supraspinal motor systems correcting and stabilizing the evoked locomotor pattern.     

Rules to limp by: joint compensation conserves limb function after peripheral nerve injury

Locomotion persists across all manner of internal and external perturbations. The objective of this study was to identify locomotor compensation strategies in rodent models of peripheral nerve injury. We found that hip-to-toe limb length and limb angle was preferentially preserved over individual joint angles after permanent denervation of rat ankle extensor muscles. These findings promote further enquiry into the significance of limb-level function for neuromechanical control of legged locomotion.     

Control of voluntary movements mediated via propriospinal neurons

Cortico- and rubrospinal tracts play an important role in controlling voluntary movements. Transection of these tracts in different spinal cord layers gives different effects that may be explained by the influence of different spinal cord neuronal networks. The aim of the present work was to study the role of C3/C4 propriospinal system in movement control and processes of motor recovery. It was shown that propriospinal system C3/C4 play crucial role in motor recovery after lesion of cortico- and rubrospinal tracts in C5, whereas ventrally located tracts are important after the same lesion in C2. More over, propriospinal system C3/C4 can mediate the command for some voluntary movements in cats.     

Experiments and models of sensorimotor interactions during locomotion

During locomotion sensory information from cutaneous and muscle receptors is continuously integrated with the locomotor central pattern generator (CPG) to generate an appropriate motor output to meet the demands of the environment. Sensory signals from peripheral receptors can strongly impact the timing and amplitude of locomotor activity. This sensory information is gated centrally depending on the state of the system (i.e., rest vs. locomotion) but is also modulated according to the phase of a given task. Consequently, if one is to devise biologically relevant walking models it is imperative that these sensorimotor interactions at the spinal level be incorporated into the control system.     

Classification of lumbosacral neurons by their discharge pattern during evoked locomotion

Unit activity was recorded in the lumbosacral division of the spinal cord during evoked locomotion in mesencephalic cats with the afferent fibers from their hind limbs intact or divided. If the afferent fibers were intact, all neurons recorded showed modulation of activity during locomotion in the rhythm of stepping movements. In experiments on cats with afferent fibers from the hind limbs divided modulation was absent in 30% of neurons, while in the modulated neurons, the frequencies in the excitation phase were approximately the same as when the limb innervation was intact. Modulation of activity in some neurons occurred in response to stimulation of the locomotor region even before stepping movements began. The tuning of the spinal generator of stepping movements is discussed.M. V. Lomonosov Moscow State University. Institute of Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 4, pp. 410–417, July–August, 1972.     

Modification of motoneuron size after partial denervation in neonatal rats

Our previous studies have shown that partial denervation of extensor digitorum longus muscle (EDL) in the rat at 3 days of age causes an increase in the activity of the intact motoneurons. The originally phasic pattern of activity of EDL became tonic after partial denervation. These modifications of motoneuron activity were associated with the change in the phenotype of the muscle from fast to slow contracting and with a conversion of the muscle fibres from a fast to a slow type. The present study investigates whether the size of the cell body of the active EDL motoneurons change in parallel with the altered muscular activity. The study involved partial denervation of rat EDL muscle by section of the L4 spinal nerve at 3 days of age. Then the remaining motoneurons from L5 spinal nerve supplying the EDL muscle were retrogradly labelled with horseradish peroxidase two months later. The results show a reduction in motoneuron size in parallel with an increase in activity of the motoneurons after partial denervation of EDL muscle.     

Examination of the Combined Effects of Chondroitinase ABC,Growth Factors and Locomotor Training following Compressive Spinal Cord Injury on Neuroanatomical Plasticity and Kinematics

While several cellular and pharmacological treatments have been evaluated following spinal cord injury (SCI) in animal models, it is increasingly recognized that approaches to address the glial scar, including the use of chondroitinase ABC (ChABC), can facilitate neuroanatomical plasticity. Moreover, increasing evidence suggests that combinatorial strategies are key to unlocking the plasticity that is enabled by ChABC. Given this, we evaluated the anatomical and functional consequences of ChABC in a combinatorial approach that also included growth factor (EGF, FGF2 and PDGF-AA) treatments and daily treadmill training on the recovery of hindlimb locomotion in rats with mid thoracic clip compression SCI. Using quantitative neuroanatomical and kinematic assessments, we demonstrate that the combined therapy significantly enhanced the neuroanatomical plasticity of major descending spinal tracts such as corticospinal and serotonergic-spinal pathways. Additionally, the pharmacological treatment attenuated chronic astrogliosis and inflammation at and adjacent to the lesion with the modest synergistic effects of treadmill training. We also observed a trend for earlier recovery of locomotion accompanied by an improvement of the overall angular excursions in rats treated with ChABC and growth factors in the first 4 weeks after SCI. At the end of the 7-week recovery period, rats from all groups exhibited an impressive spontaneous recovery of the kinematic parameters during locomotion on treadmill. However, although the combinatorial treatment led to clear chronic neuroanatomical plasticity, these structural changes did not translate to an additional long-term improvement of locomotor parameters studied including hindlimb-forelimb coupling. These findings demonstrate the beneficial effects of combined ChABC, growth factors and locomotor training on the plasticity of the injured spinal cord and the potential to induce earlier neurobehavioral recovery. However, additional approaches such as stem cell therapies or a more adapted treadmill training protocol may be required to optimize this repair strategy in order to induce sustained functional locomotor improvement.     

Neurofilamentous hypertrophy of intramedullary axonal arbors in intact spinal motoneurons undergoing peripheral sprouting

An incomplete motor nerve injury or a partial loss of motoneurons leads to a partial denervation of skeletal muscle. As part of a compensatory response, the remaining intact motoneurons undergo peripheral sprouting and increase their motor unit size. Our knowledge about the responses in the more proximal parts of these sprouting motoneurons is sparse, however. We investigated the effects of an incomplete transection of the medial gastrocnemius (MG) nerve in the adult cat on the morphology of the intramedullary axon and axon collateral systems of the remaining intact MG motoneurons. At twelve weeks following the partial transection of the MG nerve, intracellular recording and labeling techniques were used to deposit horseradish peroxidase into single intact MG motoneurons for detailed morphological studies. The light microscopic appearance and caliber of the intramedullary stem motor axons of the intact MG motoneurons were indistinguishable from controls. The number and size of the intramedullary motoraxon collateral systems were also unchanged. However, frequent and marked hypertrophy of the distal portions of the motoraxon collaterals was encountered. Electron microscopic studies of the hypertrophied collaterals demonstrated abnormal accumulations of disorganized neurofilaments arranged in bundles or whorls. The morphological changes were indistinguishable from the neurofilamentous hypertrophy that has previously been reported in Wallerian degeneration, in experimental and human motor neuron disease and in some regenerating axonal processes of spinal motoneurons. We conclude that, neurofilamentous hypertrophy of the intramedullary arbors of motor axons may also be part of a reactive and non-degenerative response in intact motoneurons undergoing compensatory peripheral sprouting.     

Thoracic Hemisection in Rats Results in Initial Recovery Followed by a Late Decrement in Locomotor Movements,with Changes in Coordination Correlated with Serotonergic Innervation of the Ventral Horn

Lateral thoracic hemisection of the rodent spinal cord is a popular model of spinal cord injury, in which the effects of various treatments, designed to encourage locomotor recovery, are tested. Nevertheless, there are still inconsistencies in the literature concerning the details of spontaneous locomotor recovery after such lesions, and there is a lack of data concerning the quality of locomotion over a long time span after the lesion. In this study, we aimed to address some of these issues. In our experiments, locomotor recovery was assessed using EMG and CatWalk recordings and analysis. Our results showed that after hemisection there was paralysis in both hindlimbs, followed by a substantial recovery of locomotor movements, but even at the peak of recovery, which occurred about 4 weeks after the lesion, some deficits of locomotion remained present. The parameters that were abnormal included abduction, interlimb coordination and speed of locomotion. Locomotor performance was stable for several weeks, but about 3–4 months after hemisection secondary locomotor impairment was observed with changes in parameters, such as speed of locomotion, interlimb coordination, base of hindlimb support, hindlimb abduction and relative foot print distance. Histological analysis of serotonergic innervation at the lumbar ventral horn below hemisection revealed a limited restoration of serotonergic fibers on the ipsilateral side of the spinal cord, while on the contralateral side of the spinal cord it returned to normal. In addition, the length of these fibers on both sides of the spinal cord correlated with inter- and intralimb coordination. In contrast to data reported in the literature, our results show there is not full locomotor recovery after spinal cord hemisection. Secondary deterioration of certain locomotor functions occurs with time in hemisected rats, and locomotor recovery appears partly associated with reinnervation of spinal circuitry by serotonergic fibers.     

Effects of neck and circumoesophageal connective lesions on posture and locomotion in the cockroach

Few studies in arthropods have documented to what extent local control centers in the thorax can support locomotion in absence of inputs from head ganglia. Posture, walking, and leg motor activity was examined in cockroaches with lesions of neck or circumoesophageal connectives. Early in recovery, cockroaches with neck lesions had hyper-extended postures and did not walk. After recovery, posture was less hyper-extended and animals initiated slow leg movements for multiple cycles. Neck lesioned individuals showed an increase in walking after injection of either octopamine or pilocarpine. The phase of leg movement between segments was reduced in neck lesioned cockroaches from that seen in intact animals, while phases in the same segment remained constant. Neither octopamine nor pilocarpine initiated changes in coordination between segments in neck lesioned individuals. Animals with lesions of the circumoesophageal connectives had postures similar to intact individuals but walked in a tripod gait for extended periods of time. Changes in activity of slow tibial extensor and coxal depressor motor neurons and concomitant changes in leg joint angles were present after the lesions. This suggests that thoracic circuits are sufficient to produce leg movements but coordinated walking with normal motor patterns requires descending input from head ganglia.Electronic Supplementary Material Supplementary material is available for this article at     

Hypoxia inhibits abdominal expiratory nerve activity

Our purpose was to examine the influence of steady-state changes in chemical stimuli, as well as discrete peripheral chemoreceptor stimulation, on abdominal expiratory motor activity. In decerebrate, paralyzed, vagotomized, and ventilated cats that had bilateral pneumothoraces, we recorded efferent activity from a phrenic nerve and from an abdominal nerve (cranial iliohypogastric nerve, L1). All cats showed phasic expiratory abdominal nerve discharge at normocapnia [end-tidal PCO2 38 +/- 2 Torr], but small doses (2-6 mg/kg) of pentobarbital sodium markedly depressed this activity. Hyperoxic hypercapnia consistently enhanced abdominal expiratory activity and shortened the burst duration. Isocapnic hypoxia caused inhibition of abdominal nerve discharge in 11 of 13 cats. Carotid sinus nerve denervation (3 cats) exacerbated the hypoxic depression of abdominal nerve activity and depressed phrenic motor output. Stimulation of peripheral chemoreceptors with NaCN increased abdominal nerve discharge in 7 of 10 cats, although 2 cats exhibited marked inhibition. Four cats with intact neuraxis, but anesthetized with ketamine, yielded qualitatively similar results. We conclude that when cats are subjected to steady-state chemical stimuli in isolation (no interference from proprioceptive inputs), hypercapnia potentiates, but hypoxia attenuates, abdominal expiratory nerve activity. Mechanisms to explain the selective inhibition of expiratory motor activity by hypoxia are proposed, and physiological implications are discussed.     

单侧前庭神经切断后猫运动方式的改变和补偿

本工作首次将一种运动分析系统,即视觉自动电视摄相信息处理系统（ｏｐｔｉｃａｌａｕｔｏｍａｔｉｃＴＶ－ｉｍａｇｅｐｒｏｃｅｓｓｏｒ,Ｅ．Ｌ．Ｉ．Ｔ．Ｅｓｙｓｔｅｍ）用于动物运动方式的定量分析,比较了猫一侧前庭神经切断前后在跨越转动横梁测试中运动方式的变化。结果如下：在横梁静止条件下,猫述后行走的初始身高明显下降,步距变短,步 频降低,呈缓慢的蹒中山步态,继而各参量逐渐增加,分别在术后４５和７０ｄ恢复     

Disorder and recovery of somatic sensitivity in cats with destruction of the afferent pathways of the spinal cord]

Somatic sensitivity was studied in intact cats and in the process of functions recovery after section of the posterior columns of the spinal cord and spino-cervical tracts. The state of somatic sensitivity was estimated by the change in the thresholds of food-procuring conditioned reflexes to electrocutaneous stimulation of the anterior limb. After section of the posterior columns or the spino-cervical tracts at the level of the 2nd cervical segment, the threshold rose. It gradually decreased in parallel to the recovery of motor activity, without reaching the initial level. The section of both tracts (simultaneous or in two stages) resulted in an intensive rise of the threshold which decreased in the course of recovery of disturbed functions. Evidently only partial recovery of somatic sensitivity takes place in the process of compensation of functions following the lesion of specific afferent ways of the spinal cord, and motor activity may be achieved with a consdierable deficit of somatic sensitivity.     

Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia

Axonal regeneration in the lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. In adult rats, olfactory ensheathing glia (OEG) transplants successfully led to functional and structural recovery after complete spinal cord transection. From 3 to 7 months post surgery, all OEG-transplanted animals recovered locomotor functions and sensorimotor reflexes. They presented voluntary hindlimb movements, they supported their body weight, and their hindlimbs responded to light skin contact and proprioceptive stimuli. In addition, relevant motor axons (corticospinal, raphespinal, and coeruleospinal) regenerated for long distances within caudal cord stumps. Therefore, OEG transplantation provides a useful repair strategy in adult mammals with traumatic spinal cord injuries. Our results with these cells could lead to new therapies for the treatment of spinal cord lesions in humans.     

Splenic reflex modulation of central cardiovascular regulatory pathways

The splenorenal reflex induces changes in mean arterial pressure (MAP) and renal function. We hypothesized that, in addition to spinal pathways previously identified, these effects are also mediated through central pathways. We investigated the effect of elevated splenic venous pressure on central neural activation in intact, renal-denervated, and renal + splenic-denervated rats. Fos-labeled neurons were quantified in the nucleus of the tractus solitarius (NTS), paraventricular nucleus (PVN), supraoptic nucleus (SON), and subfornical organ (SFO) after 1-h partial splenic vein occlusion (SVO) in conscious rats bearing balloon occluders around the splenic vein, telemetric pressure transducers in the gastric vein (splenic venous pressure), and abdominal aorta catheters (MAP). SVO stimulated Fos expression in the PVN and SON, but not NTS or SFO of intact rats. Renal denervation abolished this response in the parvocellular PVN, while renal + splenic denervation abolished activation in the magnocellular PVN and the SON. In renal-denervated animals, SVO depressed Fos expression in the NTS and increased expression in the SFO, responses that were abolished by renal + splenic denervation. In intact rats, SVO also induced a fall in right atrial pressure, an increase in renal afferent nerve activity, and an increase in MAP. We conclude that elevated splenic venous pressure does induce hypothalamic activation and that this is mediated through both splenic and renal afferent nerves. However, in the absence of renal afferent input, SVO depressed NTS activation, probably as a result of the accompanying fall in cardiac preload and reduced afferent signaling from the cardiopulmonary receptors.     

Optic nerve regeneration after intravitreal peripheral nerve implants: trajectories of axons regrowing through the optic chiasm into the optic tracts

We have studied axon regeneration through the optic chiasm of adult rats 30 days after prechiasmatic intracranial optic nerve crush and serial intravitreal sciatic nerve grafting on day 0 and 14 post-lesion. The experiments comprised three groups of treated rats and three groups of controls. All treated animals received intravitreal grafts either into the left eye after both left sided (unilateral) and bilateral optic nerve transection, or into both eyes after bilateral optic nerve transection. Control eyes were all sham grafted on day 0 and 14 post-lesion, and the optic nerves either unlesioned, or crushed unilaterally or bilaterally. No regeneration through the chiasm was seen in any of the lesioned control optic nerves. In all experimental groups, large numbers of axons regenerated across the optic nerve lesions ipsilateral to the grafted eyes, traversed the short distal segment of the optic nerve and invaded the chiasm without deflection. Regeneration was correlated with the absence of the mesodermal components in the scar. In all cases, axon regrowth through the chiasm appeared to establish a major crossed and a minor uncrossed projection into both optic tracts, with some aberrant growth into the contralateral optic nerve. Axons preferentially regenerated within the degenerating trajectories from their own eye, through fragmented myelin and axonal debris, and reactive astrocytes, oligodendrocytes, microglia and macrophages. In bilaterally lesioned animals, no regeneration was detected in the optic nerve of the unimplanted eye. Although astrocytes became reactive and their processes proliferated, the architecture of their intrafascicular processes was little perturbed after optic nerve transection within either the distal optic nerve segment or the chiasm. The re-establishment of a comparatively normal pattern of passage through the chiasm by regenerating axons in the adult might therefore be organised by this relatively immutable scaffold of astrocyte processes. Binocular interactions between regenerating axons from both nerves (after bilateral optic nerve transection and intravitreal grafting), and between regenerating axons and the intact transchiasmatic projections from the unlesioned eye (after unilateral optic nerve lesions and after ipsilateral grafting) may not be important in establishing the divergent trajectories, since regenerating axons behave similarly in the presence and absence of an intact projection from the other eye.     

Sprouting and regeneration of frog motoneurons during synapse elimination

The ability of frog axons to sprout and reinnervate during the period of synapse elimination was examined in the cutaneous pectoris muscle from young postmetamorphic frogs using histological staining of nerve terminals and postsynaptic acetylcholinesterase. Partial denervation of the cutaneous pectoris muscle during the period of synapse elimination produced rapid sprouting of the intact axons. The majority of denervated endplates were being reinnervated by sprouts within 3 days. In addition, total denervation performed by either sectioning or crushing the nerve was followed by functional reinnervation. Approximately 98% of the endplates were being reinnervated within 7 days after a nerve crush and 10 days after sectioning the nerve.