Dalhousie University (Halifax, Nova Scotia, Canada)
Frederic Bretzner, Ph.D.
Postdoctoral Fellow

Identification and Characterization of Reticulospinal Pathways

The spinal cord contains the neuronal circuitry to produce locomotion in the absence of central commands (from the brain) and sensory information (from the peripheral nervous system) in the animal and likely in the human. However in the absence of inputs from the brain, patients with spinal cord injury are unable to activate this circuit and therefore initiate locomotion. This makes it imperative to reestablish inputs from the brain to the spinal cord as part of the process to restore initiation of movement. The spinal cord injury field has shown in the last 30 years that motor recovery can be achieved to some extent by strategies or therapies directed to promote regeneration or sprouting of axons from the brain to the spinal cord. Some of these studies have reported such promising results in animal models, that clinical trials are currently underway around the world. With the spinal cord field advancing in this way, it is now essential to identify and characterize the most appropriate and suitable targets to restore initiation of movement. The reticulospinal pathways appear to play a key role, by virtue of their intermediate position between structures in the brain that initiate locomotion and the spinal interneuronal circuits that generate the locomotion. However, due to its complex organization, these reticulospinal pathways have to date received less interest from the scientific community as compared to the corticospinal tract, which originates from the motor cortex. Using genetic technologies, it is now possible to drive persistent expression of fluorescent proteins in specific neuronal populations. Such technologies enable us to permanently label neurons in transgenic mice, thus allowing us to characterize and identify these reticulospinal pathways and assess their contribution to locomotion. Our aims are to first identify and characterize the anatomical and physiological properties of these distinct classes of reticulospinal neurons. We will next determine which classes of reticulospinal neurons are necessary for locomotion, via a selective inhibition of these neurons. Lastly, we will identify classes of reticulospinal neurons which relay the commands from brain structures known to initiate locomotion, as well as the spinal interneurons to which these reticulospinal neurons send commands for the purposes of generating locomotion. In understanding the physiological properties of these reticulospinal neurons and their connectivity, we will have a better understanding of their role in the locomotor network. These experiments will allow us to identify and characterize the appropriate centers in the brain and at the level of the spinal cord that are important for locomotion. This is essential in the development of strategies aimed at restoring initiation of movement following spinal cord injury.