Serotonergic Modulation of Motoneuronal Excitability and Its Impact on Muscle Force Generation: A Computational Study

This study investigates the impact of serotonin (5-HT) on motoneuron electrical activity and muscle force generation. Using a computational model, we explore how 5-HT receptors influence motoneuron excitability and muscle function at different stimulation frequencies. Our results demonstrate that physiological 5-HT release increases motoneuron excitability, particularly at higher frequencies (40 Hz and 100 Hz), consistent with the known excitatory role of serotonin through 5-HT2a receptor activation. However, high concentrations of 5-HT lead to decreased motoneuron excitability, potentially due to excessive activation of 5-HT1a receptors, which are involved in neuronal hyperpolarization. The generated muscle force exhibited a direct correlation with motoneuron activity. At 10 Hz, physiological 5-HT release did not significantly affect force production, suggesting minimal impact at low frequencies. However, high 5-HT concentrations reduced contraction duration, indicating muscle fatigue. At 40 Hz and 100 Hz, physiological 5-HT release enhanced motoneuron excitability, promoting more sustained muscle responses. Nevertheless, high serotonin concentrations decreased the ability to maintain muscle contraction, leading to fatigue. Our findings align with experimental studies, validating the model as an effective tool for understanding the role of serotonin in neuromuscular function. The model provides insights into the mechanisms underlying muscle fatigue and could serve as a foundation for developing therapeutic strategies to modulate serotonergic signaling, improving muscle performance and recovery. Future research should explore the interactions with other neurotransmitters to further investigate their effects on motor function and fatigue resistance.