Functional contribution of glutamatergic neurons of medullary reticular nuclei to locomotor recovery after spinal cord injury

Abstract

Spinal cord injury (SCI) disrupts the descending drive from the brain and causes a range of deficits. We have investigated the functional plasticity of the glutamatergic reticulospinal drive of the medullary reticular formation (MRF) after a lateral thoracic hemisection in mice. The excitatory descending drive was impaired after SCI, independently of its origin. The direction of functional plasticity was anti-correlated with its pre-injury efficacy. Stimulation of sites in the most dorsal MRF decelerated or stopped locomotion, whereas the most ventral sites increased speed. The ability to steer was preserved with modest impairment. Activating the descending MRF drive improved stepping ability of chronically impaired SCI mice and its conditioning improved recovery of skilled locomotion. These results highlight the resilience and capacity for reorganization of the glutamatergic reticulospinal command after SCI, along with its suitability as a therapeutical target to promote functional recovery.