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.

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.

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.

Chapter 16--spinal plasticity in the recovery of locomotion.

Locomotion is a very robust motor pattern which can be optimized after different types of lesions to the central and/or peripheral nervous system. This implies that several plastic mechanisms are at play to re-express locomotion after such lesions. Here, we review some of the key observations that helped identify some of these plastic mechanisms. At the core of this plasticity is the existence of a spinal central pattern generator (CPG) which is responsible for hindlimb locomotion as observed after a complete spinal cord section. However, normally, the CPG pattern is adapted by sensory inputs to take the environment into account and by supraspinal inputs in the context of goal-directed locomotion. We therefore also review some of the sensory and supraspinal mechanisms involved in the recovery of locomotion after partial spinal injury. We particularly stress a recent development using a dual spinal lesion paradigm in which a first partial spinal lesion is made which is then followed, some weeks later, by a complete spinalization. The results show that the spinal cord below the spinalization has been changed by the initial partial lesion suggesting that, in the recovery of locomotion after partial spinal lesion, plastic mechanisms within the spinal cord itself are very important.

Study of cutaneous reflex compensation during locomotion after nerve section in the cat.

In the cat, section of all cutaneous nerves of the hindfeet except the tibial (Tib) nerve supplying the plantar surface results in a long-lasting decrease in the intensity of Tib stimulation needed for a threshold response in flexor muscles and an increase in the amplitude of the phase-dependent responses recorded in various muscles during locomotion. Stimulating through chronically implanted nerve cuffs ensured a stable stimulation over time. The increase in reflex amplitude was well above the small increase in the amplitude of the locomotor bursts themselves that results from the denervation. Short latency responses (P1) were seen in flexor muscles, especially at the knee (semitendinosus) and ankle (tibialis anterior and extensor digitorum longus), with stimuli applied in the swing phase and also to a lesser degree in the later part of the cycle. Longer latency responses (P2) were increased in hip, knee, and ankle flexors, as well as in a contralateral extensor (vastus lateralis) when applied in late stance. Responses evoked from stimulating the proximal end of sectioned nerves were not larger than before neurectomy. This suggests that the increased responsiveness to Tib stimulation is not simply caused by an increase in motoneuron excitability, because this would have resulted in a nonspecific increase of responses to stimulation of any nerve. It is concluded that the adult locomotor system is capable of central reorganization to enhance specific remaining cutaneous reflex pathways after a partial cutaneous denervation of the paw.

Nonlocomotor and locomotor hindlimb responses evoked by electrical microstimulation of the lumbar cord in spinalized cats.

As a preliminary step to using intraspinal microstimulation (ISMS) for rehabilitation purposes, the distribution of various types of hindlimb responses evoked by ISMS in spinal cats (T(13)) is described. The responses to ISMS applied through a single electrode was assessed, before and after an intravenous injection of clonidine (noradrenergic agonist), using kinematics and electromyographic recordings in subacute (5-7 days, untrained) or chronic (3-5 wk trained on a treadmill) spinal cats. ISMS was applied in the dorsal, intermediate and ventral areas of segments L(3)-L(7), from midline to 3 mm laterally. Uni- and bilateral non-locomotor responses as well as rhythmical locomotor responses were evoked. In the subacute cats, ipsilateral flexion was elicited in the dorsal region of L(3)-L(7), whereas ipsilateral extension was evoked more ventrally and mainly in the caudal segments. Dorsal stimuli could induce ipsilateral flexion followed by ipsilateral extension. Sites inducing bilateral flexion and bilateral extension were similarly distributed to those evoking ipsilateral flexion and extension in the rostrocaudal axis but were evoked from more medial sites. Ipsilateral flexion with crossed extension was evoked from intermediate and ventral zones of all segments and lateralities. Unilateral ipsilateral locomotion was rarely observed. Contralateral locomotion was more frequent and mainly evoked medially, whereas bilateral locomotion was evoked exclusively from dorsal regions. With some exceptions, those distribution gradients were similar in the four conditions (subacute, chronic, pre- and postclonidine), but the proportion of each response could vary. The distribution of ISMS-evoked responses is discussed as a function of known localization of interneurons and motoneurons.