Grant: Project Grant

Locomotion is a basic, crucial motor act for quality of life. The organization of the neural structures responsible for controlling locomotion is highly conserved in all vertebrate animal species, including humans. Neural networks in the spinal cord generate the basic muscle activations during locomotion. Supraspinal structures on the other hand are essential to start, maintain, and stop locomotion, as well as to change direction and speed. Reticulospinal neurons are the most important source of supraspinal descending outputs to the spinal cord, and if their descending axons and spinal connections are severed after spinal injury, individuals can no longer voluntarily control their locomotion, with dire consequences. Over recent decades, there has been a large improvement in our understanding of how spinal networks generate locomotion and how the supraspinal structures control locomotor behavior. It has been known for some time that connections between descending axons and spinal neurons involved in locomotion are subject to presynaptic modulation. However, the targets and mechanisms involved have not been characterized in any detail. This proposal is aimed at providing new knowledge on this modulation of descending axon transmission. We propose to use imaging techniques specifically developed and adapted by us as well as electrophysiological and neuroanatomical approaches to characterize presynaptic modulation of descending axon transmission in the spinal cord, at rest and during locomotion. We will use a form of light sheet imaging that enables us to resolve synaptic responses in 3D at high speed and for hours, without causing photodamage. Understanding how the transmission from descending axons is modulated during locomotion should provide important insights for developing new strategies in the treatment of spinal cord injured patients.