Renshaw hücrelerinin sinaptik fizyolojisinin incelenmesi ve bu hücrelerin motor nöron hasarındaki rolü

Among the circuits of interneurons within the spinal cord, the Renshaw's inhibitory circuit is known to directly feedback on alpha-motoneurons. Inhibitory Renshaw cells (RCs) are located in the ventral horn of the spinal cord. Their unique features such as receiving direct cholinergic input from alpha-motoneurons and their ability for burst-firing provide a suitable model for studying circuits of the spinal cord. Although RC circuitry has been investigated for more than 70 years, its exact function has yet to be discovered due to the limitation of techniques. Therefore, the aim of this thesis was to develop a reliable method to investigate the characteristics of recurrent inhibition in healthy people and pathophysiology of RCs in patients who suffer from amyotrophic lateral sclerosis (ALS). After optimizing the stimulation parameters of the motor axons in a reproducible manner, we recorded single motor units and analyzed the individual sets of action potentials using probability as well as frequency-based analysis. For this purpose, the largest motor axons in the tibial nerve were electrically stimulated to activate RCs antidromically and the smallest motor units innervating soleus muscle were recorded using intramuscular electromyography in healthy people and ALS patients. The frequency methods indicated that the duration of the recurrent inhibition was between 30 to 55 ms in healthy people depending on the background firing rate of single motor units which were inversely proportional. Moreover, we found an evidence to support a longer inhibition on smaller diameter alpha-motoneurons compared to larger ones. On the other hand, the efficiency of the RCs was extremely reduced in the lumbar-affected ALS patients, i.e. the recurrent inhibition duration was about 11 ms, one-third to one-fifth of the healthy people. These findings indicate a high correlation with the controlled animal studies, and that this method can be used as a reliable tool to shed more light on the functions and dysfunctions of the RC system in humans. Moreover, the outcome from this thesis provides evidence about the involvement of last-order interneurons, e.g. RCs, in the development of movement disorders, such as ALS.