New Insights into the Spinal Recurrent Inhibitory Pathway Normally and After Motoneuron Regeneration
Francisco Alvarez Leefmans (Committee Member), Steven Berberich (Committee Member), Timothy Cope (Advisor), Sherif Elbasiouny (Committee Member), David Ladle (Committee Member), Mark Rich (Committee Member)
Doctor of Philosophy (PhD)
Despite more than seven decades of intensive research, uncertainty is the hallmark of spinal recurrent inhibition. The simplest possible structure that is formed between the a-motoneuron and its inhibitory interneurons has been the subject of long lasting scientific debate. To date, there is no consensus on the functional significance of this circuit. Even the simplest assumption of a negative feedback loop does not hold true. The current work used the technique of in vivo intracellular recording from the adult rat a-motoneurons to study the normal function and the plasticity after nerve injury and regeneration of this simple, yet intricate spinal circuit. The long lasting notion that inhibition must adversely affect neuronal firing rates has been challenged and the counter-intuitive finding that recurrent inhibition can increase firing rate under certain circumstances is reported for the first time. In addition, recurrent inhibition was found to strongly affect action potential spike timing and was found to prolong the duration of repetitive firing of a-motoneurons. Furthermore, the circuit behavior at different frequencies has been examined and novel findings are reported. The circuit adaptation to peripheral nerve injury and successful regeneration was studied. Results showed that peripheral nerve regeneration failed to restore the structure and function of this central circuit. In conclusion, the current thesis calls for a reevaluation of the concept that recurrent inhibition must suppress a-motoneuron firing and suggests that inhibition in general plays more of a role in modulating firing behavior. Finally, another example of permanent central nervous system dysfunction despite successful peripheral recovery is reported and perhaps adds to the permanent functional deficits that remain in victims of peripheral nerve injury.
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