UC San Diego

All living organisms have the innate need to interact with their environment in order to ensure their survival and reproductive success. Among vertebrates, the somatomotor system plays a critical role in responding to environmental challenges and opportunities by coordinating the movements of the body through the activation of its primary effector organs, the skeletal muscles. However, the execution of somatomotor activities is contingent upon maintaining a controlled internal environment that can adapt to the demands imposed by these actions. In this regard, the endocrine and autonomic nervous systems play vital roles by regulating the activity of internal organs and adjusting the composition of the internal milieu in response to both external and internal perturbations. While the endocrine system acts slowly and exerts long-lasting effects on physiological processes, the autonomic nervous system employs rapid neuronal communication to achieve short-lived adjustments in the activity of its target effector organs. By working in tandem, the autonomic nervous system and the endocrine system maintain the overall physiology of the organism across different timescales, ensuring optimal conditions for survival and reproductive success. The autonomic nervous system comprises two divisions, namely the sympathetic and parasympathetic divisions, which have traditionally been considered to work in opposition to each other. This conceptualization was influenced by the work of physiologists like Walter Cannon, who emphasized the role of the nervous system in maintaining homeostasis. Cannon associated the sympathetic nervous system with the unitary physiological responses observed during fight-or-flight behaviors. However, another group of researchers, primarily interested in understanding the neural control of the sympathetic nervous system, highlighted the diverse patterns of activities generated by this system. They proposed that the sympathetic nervous system is capable of exerting differential control over the effector organs. These findings challenged the notion of a unitary response and gave rise to an alternative perspective on the function of the sympathetic nervous system. As a result of these historical developments, we now have two leading ideas regarding the sympathetic nervous system: the homeostatic view, emphasizing its role in coordinating the body's responses to stress and maintaining physiological balance, and the perspective highlighting the differential control and diverse patterns of activity generated by the sympathetic division. These two ideas reflect different aspects of the complex and multifaceted nature of the sympathetic nervous system. The differential control of the sympathetic nervous system, characterized by the decoupled activation of effector organs, has been a driving force in neuroscience research. While medicine has adapted the homeostatic view, the field of neuroscience has explored the patterns of responses within the sympathetic nervous system. Through behavioral, physiological, neurophysiological, and neuroanatomical studies, researchers have provided evidence for the generation of various activity patterns by the sympathetic nervous system. The remaining challenge has been to uncover the mechanisms underlying this differential control. Neuroanatomical investigations have played a crucial role in understanding the functional organization and the differential control of the sympathetic nervous system. Building upon the ideas of Sherrington, anatomical dissections have revealed a hierarchical structure. At each level of this hierarchy, reflexes are integrated within the central and peripheral nervous system. Each level of the hierarchy has been a focus of research to elucidate its specific role. Anatomically these levels correspond to sympathetic ganglia, sympathetic motor neurons, premotor neurons and the higher centers that have top-down influences on the lower centers of the sympathetic nervous system. This dissertation primarily focuses on the lower centers of the hierarchy and aims to provide molecular and circuit-level dissections of each layer of the sympathetic circuitry, from the sympathetic ganglia to the spinal premotor neurons. Modern tools such as sequencing and tracing techniques, which have been refined over the past two decades, have been employed to gain insights into the functions of these neural components. By leveraging these advanced techniques, this dissertation seeks to enhance our understanding of the lower centers of the sympathetic circuit and their contributions to the overall control of sympathetic activity.