Propriospinal Plasticity and Recovery After Incomplete Spinal Cord Injury.

Project Summary/Abstract: After a spinal cord injury (SCI) some neurons undergo anatomical expansion of their terminal fields via collateral sprouting that may be adaptive, leading to improved recovery, and/or maladaptive, leading to reduced recovery. However, as a field we have had few opportunities to directly link observed anatomical plasticity of spinal cord interneurons with functional changes. We have used virus-based tools to synaptically silence or anatomically trace specific spinal cord interneurons, the long-ascending propriospinal neurons (the LAPNs) that reside at L2 and project to C6, segments critical for hindlimb and forelimb activity during locomotion. Our recent work suggests that LAPN plasticity after a SCI may be maladaptive and impede or limit functional recovery. In combination with iDISCO tissue clearing and confocal imaging we are studying their dendritic and axonal anatomy before and after a variety of SCIs in the adult rat. In addition, our main collaborator on this project will enable us to use tried and true anterograde tract tracing to characterize interactions between reticulospinal axons and the LAPNs, before and after a contusive spinal cord injury and following a standard lateral hemisection injury. For both video and machine-learning aided locomotor analysis and as a novel activity/training strategy we use a 10 foot long plexiglass tank that allows the animals to run back and forth expressing the full range of speed-dependent gaits and gait transitions. With these tools we will investigate the anatomical plasticity exhibited by LAPNs after a T9 contusion injury in male and female SD rats, and in females only with and without acute or chronic activity/training (Aim 1), the impact of silencing the LAPNs on both acute functional recovery and chronic recovered function after a T9 injury (Aim 2) and the roles the LAPNs play in recovered function following a lateral hemisection where the silenced LAPNs are either spared or axotomized (Aim 3). These studies will have translational importance for cell and drug therapies in addition to neuromodulation approaches including epidural and transcutaneous spinal cord stimulation and will allow us to address the confusing adaptive/maladaptive concepts driving the neuroanatomical-functional paradox that plagues the field of spinal cord injury.