Central Noradrenergic Neuron Subtype Development and Function

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Noradrenergic (NE) neurons, the cells of the nervous system that actively synthesize norepinephrine, play an essential role in circuits governing attention, mood, appetite, memory, anxiety and stress. In addition, NE neurons provide pivotal support for autonomic function in the peripheral nervous system. Consequently, abnormal function of NE neurons is implicated in a broad spectrum of neurological disorders such as depression, post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), Parkinsons disease, Alzheimers disease and Down syndrome. In several of these disorders there is evidence that unique subpopulations of NE neurons are selectively affected. Further diversity among NE neurons is illustrated by their anatomical location, cell morphology, axonal projection pattern, neuropeptide expression and vulnerability to environmental factors. Mechanisms that determine such features are currently unknown, and no molecular markers that are capable of distinguishing physiologically relevant NE neuron subtypes have been identified. Such knowledge is central to understanding why select subpopulations of NE neurons are differentially susceptible to disease and environmental insult. To begin filling this knowledge gap, we are investigating the origin, development and function of genetically defined subsets of NE neurons in the mouse central nervous system through the application of a novel set of recombinase-based genetic tools.