Effects of Age and Exercise on Neuromuscular Junction Plasticity in Muscles of Swallowing and Voice

Sarcopenia, the loss of muscle mass and strength with aging, affects skeletal muscle throughout the body, including muscles in the tongue and larynx. These changes negatively impact muscle function and have been implicated as major contributors to swallowing and voice disorders in elderly people. One mechanism of sarcopenia may be age-related changes in neuromuscular junction (NMJ) morphology and physiology. Progressive resistance exercise training in the limb musculature has been found to prevent and/or reverse the effects of sarcopenia and reduce age-related changes at the NMJ. However, the impact of exercise on the aging muscles of the cranial sensorimotor system is unknown.;This research investigated the effects of age and exercise on NMJ morphology in one muscle of swallowing (genioglossus/GG) and one of voice (thyroarytenoid/TA) using two different models of exercise in a rat: bilateral neuromuscular electrical stimulation (NMES) and behavioral vocalization training. Additionally, the behavioral impact of the vocal training was assessed through acoustic analysis of ultrasonic vocalizations (USVs).;Results showed both models of exercise reduced age-related changes in NMJ morphology. In the GG, the relationship between motor endplates and nerve terminals was negatively affected by age but was restored with NMES. The mean and variability of motor endplate volume in old rats also decreased with NMES. In the TA, aging was associated with increased pre-synaptic remodeling and motor endplate instability; vocal training reduced motor endplate instability and decreased variability in NMJ morphology measures. Acoustic analysis showed USV amplitude was smaller with age, but this was mitigated with vocal training. Significant correlations were found between USV acoustics and NMJ morphology in the TA, indicating changes in vocal function are related to changes in underlying neuromuscular mechanisms.;This dissertation demonstrated how two models of exercise reduced the effects of age on NMJs in muscles of swallowing and voice. Additionally, it was the first study to show vocal training impacts both vocalizations and laryngeal neuromuscular adaptations. This research has provided meaningful findings that can be used to develop hypotheses to test in human participants and pave the way for evidence-based interventions.