Serotonergic neurons modulating locomotion and autonomic support for movement
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Much of the present-day research on brainstem and spinal cord control of locomotion is primarily focused on the neurotransmitter glutamate. However, evidence suggests that monoamines, such as serotonin, may initiate or modulate locomotion. This dissertation aimed to investigate the involvement of caudal brainstem serotonin neurons in locomotion. The results indicated that while selective stimulation of 5-HT neurons could occasionally initiate fictive locomotor episodes, it predominately led to increases in tonic electroneurogram activity. This suggests that 5-HT stimulation can enhance the excitability of locomotor central pattern generators, and sometimes elicit rhythmic activity. One unexpected outcome from this study was the strong correlation between locomotion and autonomic activity, specifically blood pressure increases with 5-HT neuron stimulation. This study provides evidence that a small subset of 5-HT neurons can have dual roles, regulating both locomotor and autonomic function. It has been proposed that the rostral ventrolateral medulla (RVLM) may serve as an integrator of locomotor and autonomic function. Chapter IV provides a proof-of-concept study highlighting the utility of the decerebrate rat preparation to study the RVLM as the final integrator for locomotion and autonomic support. Specifically, it provides a framework to study how the RVLM may be able to coordinate metabolic support with ongoing movement. The results of this dissertation suggest that future research on locomotor systems should also incorporate autonomic measures to better understand the interconnectedness between these two systems. Further, it has emphasized the need for more research on 5-HT’s ability to act within multifunctional neural circuits. This dissertation also explored the outputs of the CPG, specifically by using a broad-spectrum potassium (K+) channel blocker called 4-aminopyridine (4-AP). Systemic administration of 4-AP resulted in an increase in frequency and synchronized bursts in functionally different nerves, highlighting the adaptability of the locomotor central pattern generator. The observed frequency can reach up to 6-7 Hz. This study suggests a differential distribution of K+ channels on inhibitory interneurons due to the persistence of synchronous activity. In addition, there may be coupling with sympathetic preganglionic neurons as there were concurrent increases in blood pressure. Further dosing studies