Spinal cord injury (SCI) is a debilitating disease process that results in decreases in voluntary control of muscles and the presence of multi-joint spasms. Recent data suggest alterations in the neuromodulatory control of spinal motoneurons contribute to these motor behaviors; however, the actions of spinal interneurons on motor output following SCI are poorly understood. The scientific goal of this Post-Doctoral Fellowship is to understand the functional reorganization of spinal interneurons following SCI using combined electrophysiological, surgical, and pharmacological approaches in the hindlimb of the unparalyzed, unanesthetized decerebrate cat. Using this model, the application of high density electrode arrays will allow us to gather motor unit spike timing from multiple muscles simultaneously with the activity of multiple spinal interneurons via extracellular electrodes. Coherence analysis between the motor unit and interneuronal firing patterns will allow us to estimate the synaptic input which is common between recordings. Previous data indicate an acute dorsal hemisection will increase common synaptic input to motoneurons; we believe this is due to a selective depletion to serotonin (5HT) to dorsal horn interneurons, which disinhibits interneurons through inactivation of the 5HT1 receptor subtype. We will extend this framework over 2 aims: Aim 1 will classify modulatory states which regulate common synaptic input to motoneurons, while Aim 2 will identify the functional reorganization of spinal pre-motor interneurons following chronic SCI. This approach will be used to understand changes in the modulatory regulation of spinal interneurons following acute and chronic spinal lesions. This approach will advance a new understanding of spinal interneurons following SCI, provide us with potential therapeutic targets, develop a powerful model for future experimentation, and provide an excellent training environment. Importantly, the approach developed here will allow for parallel humans investigations and may provide a clinically feasible tool to assess spinal interneuron activity in patients with SCI.
|Effective start/end date||7/1/13 → 3/31/16|
- Craig H. Neilsen Foundation (AGMT Signed 4/24/2013)
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