Activity dependent stimulation increases synaptic efficacy in spared pathways in an anesthetized rat model of spinal cord contusion injury

Objective The purpose of this study was to assess the ability of intraspinal microstimulation, triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury. Approach Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. Four weeks after SCI, and under ketamine/xylazine anesthesia, fine wire electromyographic (EMG) electrodes were implanted into four muscles of the right hindlimb. After exposure of the left motor cortex hindlimb area and laminectomy of the T13-L1 vertebrae, intracortical microstimulation (ICMS) and intraspinal microstimulation (ISMS) were used to determine the location of evoked hip movements in cortex and spinal cord, respectively. For activity-dependent stimulation sessions, a single shank, 16-channel, recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. Spinal cord injured rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Activity-dependent stimulation sessions were conducted in three consecutive 1-hour conditioning bouts for a total of 3 hours. At the end of each conditioning bout, changes in synaptic efficacy were assessed using ICMS to examine the number of spikes evoked in spinal cord neurons during five minute test bouts. Evoked spikes were recorded, sorted, and displayed in post-stimulus spike histograms in 1-ms bins. Post-stimulus spike histograms and EMG recordings were characterized using stimulus triggered averaging techniques. Main results The results showed that activity-dependent stimulation resulted in an increase in cortically-evoked spikes in spinal cord neurons at specific combinations of spike-ISMS delays and numbers of pulses. Efficacy in descending motor pathways was increased throughout all dorsoventral depths of the hindlimb spinal cord, including the ventral horn, in the vicinity of motor neurons. Changes were evident in some conditions as early as 1 hour after conditioning. EMG responses were never evoked with ICMS pre-or post-conditioning. Significance These results show that after a spinal cord contusion injury, activity-dependent stimulation, consisting of cortical spike-driven ISMS, can increase synaptic efficacy in spared pathways between motor cortex and spinal cord. This suggests that activity-dependent stimulation may serve as an effective therapeutic approach for enhancing descending motor control after spinal cord injury.