Dataset for Limb disuse, synaptic maladaptation, and recovery impairments in female rats with T9 contusion SCI

STUDY PURPOSE: Use-dependent plasticity after spinal cord injury improves neuromotor functions, yet the optimal timing for initiating rehabilitation remains controversial. Little work has explicitly identified the burden of early inactivity: the biological impact of acute disuse and concomitant bedrest on long-term recovery after spinal cord injury. To test the impact of inactivity, we developed a rodent model of acute phase hindlimb-unloading in contusive thoracic spinal cord injury. DATA COLLECTED: Subjects (n=156 Female Sprague-Dawley rats) received SCI at vertebral T9 or sham SCI followed by transient hindlimb-unloading (either EARLY HU: 2 weeks of hindlimb-unloading at 3-17 days post-injury, then hindlimb-reloading until 8 weeks post-injury, DELAYED HU: 2 weeks of hindlimb-unloading at 45 days post-injury, then until 11 weeks post-injury; Just after HU: animals that were sacrificed immediately following early HU; or control). Measures of recovery included locomotor recovery (Basso Beattie Bresnahan Locomotor Scale), physiology (H reflex), kinematics quantitative biochemistry, and confocal microscopy. Unsupervised machine learning tools were also used to derive multivariate effects of hindlimb unloading. DATA USAGE NOTES: Transient hindlimb-unloading in acute spinal cord injury produced persistent (>8 weeks) impairments in hindlimb neuromotor coordination relative to normally-loaded controls on open field locomotion and kinematic measures. Reloading failed to restore function after acute hindlimb-unloading, suggesting that early limb disuse blocks subsequent use-dependent recovery after spinal cord injury. Early disuse also increased spastic posture in swim testing and reflex hyper-excitability by physiological measures (H-reflex testing; interlimb reflex), suggesting chronic hyper-excitability of spinal circuitry after spinal cord injury. Quantitative biochemistry of lumboventral synaptoneurosomes revealed that early disuse produced persistent changes in synaptic glutamate AMPA receptor subunit composition at motoneuron synapses, reducing synaptic levels of the calcium-blocking GluA2 subunit and increasing calcium-dependent phosphorylation of serine 831 on GluA1. Findings suggest that acute hindlimb-unloading drives AMPAR mediated-maladaptive synaptic plasticity in chronic spinal cord injury, and indicate that early disuse encodes a synaptic signature that undermines future recovery.