Optogenetic stimulation of glutamatergic neurons of the medullary reticular formation to promote the recovery of voluntary locomotor functions
Funded in: 2017, 2018, 2019
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Problem: Spinal cord injury (SCI) causes impairments of voluntary motor control.
Target: Plasticity of descending projections originating directly from glutamatergic neurons of the medullary reticular formation and from the cortico-reticulospinal pathway
Goal: Enhancing or activating plasticity of the reticulospinal and cortico-reticulospinal pathway to promote recovery of voluntary motor control after SCI.
Introduction: Following SCI, several projections from higher brain centers are severed, causing severe impairments of voluntary motor commands. A body of evidence has accumulated regarding the anatomical plasticity of descending commands from reticulospinal neurons. These brainstem neurons are a relay to the spinal cord for higher brain centers generating motor behaviour, including the motor cortex involved in planning voluntary movements. Following an injury, the brain has the ability to adapt up to a certain extent. This phenomenon is known as functional plasticity.
Problem statement: The loss of volontary motor control in SCI patients might be attributable to weak or absent plasticity of the cortico-reticulospinal pathway. We thus propose to trigger or enhance the plasticity within the reticulospinal and cortico-reticulospinal pathways.
Methods: We will use optogenetic tools with viral delivery readily accessible in mice. We will probe the motor output with kinematic and electromyographic recordings during voluntary locomotor tasks. We will test the effect of stimulating directly glutamatergic reticulospinal neurons or indirectly via the cortico-reticulospinal pathway prior and after SCI.
Expected results: These experiments will provide a portrait of endogenous functional plasticity occurring after lesions. We will next test the possibility of enhancing ongoing plasticity or even initiating plasticity within the reticulospinal pathway in case it is absent or weak. Finally, we will extend our investigation to the cortico-reticulospinal pathway.
Potential application: Because the motor cortex is easily accessible in comparison to the brainstem, it would suit as a convenient target for clinical treatment of SCI patients.