The sympathetic nervous system is a key regulator of whole body physiology. A dysfunctional sympathetic nervous system is linked to a growing list of human disorders including chronic heart failure, hypertension, and insulin resistance. Despite decades of research on sympathetic neurons, satellite glia, the major glial cells in sympathetic ganglia, have remained an enigmatic component of the system. Satellite glia tightly ensheathe sympathetic neuron cell bodies. In recent work, we revealed a role for satellite glial cells in restricting neuron activity to thereby modulate sympathetic output to peripheral organs. Our findings suggest that sympathetic neurons and their surrounding satellite glia should be considered as structural and functional units that orchestrate the formation and functioning of the sympathetic nervous system. However, satellite glia are a vastly under- studied cell type in the nervous system, with limited understanding of their development, neuron-glia communication, and how they contribute to neural circuits. This application addresses this knowledge gap by seeking to define how sympathetic neuron-satellite glia units are established during development, and how perturbations in this process impact neuronal connectivity and function. Based on our preliminary results, we hypothesize that target-derived neurotrophin signaling in sympathetic neurons instructs contact-based interactions with neighboring satellite glia during development. The goal of this application is to test this hypothesis and define the molecular underpinnings of this bi-directional neuron-satellite glia interactions using genetic mouse models, neuron-glia co-cultures, biochemistry, and imaging. Our studies will establish a fundamental knowledge of how these poorly studied glial cells contribute to nervous system connectivity and function and will inform new strategies for treating disorders linked to sympathetic dysfunction.