The organization of spinal neurons following spinal cord injury

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Project Summary/Abstract Spinal cord injury (SCI) is a life-changing event that sets in motion profound alterations in motor output, sensory processing, and reflex activity. Immediately following injury there is a depression of motor activity mediated by a lack of descending drive. In the weeks and months following injury, a reorganization of spinal neurons (both motoneurons and interneurons) occurs in response to this altered milieu. This includes changes in the excitability and reorganization of remaining pathways through strengthening of latent connections and neuronal sprouting. SCI induced changes in the excitability of spinal motoneurons have a profound effect on their discharge characteristics and ultimately on the generation of muscle force for functional movements. The reorganization of spinal interneurons is less well understood, even though the overwhelming majority of synaptic drive to motoneurons is mediated by spinal interneurons. Therefore, this project will explore how spinal interneurons regulate the discharge of spinal motoneurons. We will combine intraspinal microelectrode arrays with arrays on the muscle to record the individual discharges of spinal interneuron and motor unit populations. On these data, we will bring to bear advanced statistical modeling to electrophysiology dissect the organization of spinal neurons through the quantification of the strength and directional effects of these excitatory/inhibitory connections. We will use this approach to quantify the organization of spinal neurons in the intact cord and following either chronic or acute SCI. Further, we will explore the effects of neuromodulation by targeting specific serotoninergic receptor subtypes. The expected outcome of this work is a new understanding of the function of the mammalian spinal cord and the capabilities for reorganization of spinal neurons following both chronic and acute spinal transections. This approach will be a platform for characterizing the synaptic input from spinal interneurons to motoneurons and how this ultimately produces movement. Our combined motor unit and interneuron approach will directly quantify the neural substrate underlying motor unit discharge patterns and will provide a strong basis for motor unit discharge patterns to be a detailed biomarker for quantifying the state of spinal interneurons in humans with SCI.