Mechanisms of locomotor plasticity after partial section of the spinal cord: role of neural activity

点击翻译按钮获取中文摘要

In all vertebrates including humans, locomotion is controlled by three components: 1) a spinal locomotor circuitry (SLC) localized in the lumbosacral spinal cord; 2) peripheral sensory inputs; 3) descending supraspinal inputs. A long-standing and fundamental question in motor control research is: What is the relative contribution of each component to the control of locomotion? This question is complex since the three control components continuously interact to adapt the locomotor pattern to the constraints imposed by our environment. Lesion studies, by virtually isolating some components from each others, have provided important insights in the control of locomotion. In case of complete spinal sections isolating the SLC from supraspinal structures, hindlimb locomotion can be re-expressed under pharmacological, electrical and/or or afferent input stimulation. These studies demonstrate that the SLC itself is able to autonomously generate the basic pattern of locomotion, provided that the SLC is maintained in a sufficient state of excitability. However, whether the re-expression of locomotion after partial spinal sections relies on similar mechanisms is still unclear. My previous work shows that, after spinal cord hemisections severing sensorimotor tracts on one side, re-expression of locomotion occurs spontaneously with minimal sensory inputs within three weeks. What are the mechanisms supporting the re-establishment of locomotor control and what structures contribute? Possibilities include: a) the SLC below the hemisection that can assume a greater role in generating the hindlimb locomotor pattern; b) several supraspinal structures that can compensate for the loss of other descending pathways provided they can somehow reach the SLC. By using dual lesion approaches and electrophysiology techniques, our work has provided evidence that a critical link to the re-establishment of locomotor control is plasticity within both the SLC and the motor cortex. However, the relative or joint contribution of these structures to the re-establishment of locomotor control is unknown. This is in part due to the lack of ability to directly and selectively manipulate spinal and cortical neurons with temporal precision in the chronic mammal models currently used for locomotion studies. To circumvent these limitations, we will use remote activation approaches to manipulate cortical and spinal activity in mice. Over traditional approaches, these technologies uniquely enable to selectively manipulate the excitability of neurons to link circuits with behaviour. This completely original proposal has the potential to greatly expand our knowledge on the plasticity mechanisms involved in the reestablishment of locomotor control after spinal sections.