Janyne Provencher

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.

Chapter 12 The cat model of spinal injury

Publisher Summary This chapter discusses the changes occurring in the spinal cord that may lead to the re-expression of motor patterns such as hind-limb locomotion. The chapter reviews some aspects of locomotor training with and without the use of drugs, the evolution of pharmacological receptors below the level of lesion. It also discusses the role of various neurotransmitter systems before and after spinalization, the key role played by certain rostral lumbar segments of the spinal cord in the generation of locomotion, and the necessity of cutaneous inputs from the pads for the expression of spinal locomotion. The chapter discusses the recovery of locomotion in adult spinal cats is probably the result of numerous plastic changes occurring at the level of the sensory afferents, cellular properties of neurons and receptors for neurotransmitters. The spinal cord is a complex laminar and segmental structure.

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.

Chapter 16 Locomotor recovery in chronic spinal rat: long-term pharmacological treatment or transplantation of embryonic neurons?

Publisher Summary This chapter develops a strategy to supply the sublesional spinal cord with missing supraspinal neurotransmitters by two different approaches to stimulate and improve functional recovery of locomotor activity in spinal rats. The first one is through transplantation of embryonic raphe neurons as a continuous and endogenous source of serotonin (5-HT), and the second one is through a more classical pharmacological approach. The strategy of transplantation of embryonic neurons does not restore the voluntary control of locomotor movements because the connections between the brain and the central pattern generator network (CPG) remain interrupted. However, it stimulates the spinal cord for a long time and, thus allows triggering of locomotor activity using exteroceptive stimuli. If used together with a strategy of translesion reconnection, it could improve the recovery of voluntary control of locomotor activity.

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.

Cholinergic mechanisms in spinal locomotion—potential target for rehabilitation approaches

Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.