Central Noradrenergic Neuron Subtype Development and Function

National Institute Of Environmental Health Sciences

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Linked publications & trials

Abstract

Noradrenergic (NA) neurons, the cells of nervous system that actively synthesize norepinephrine, play an essential role in circuits involving attention, mood, appetite, memory, anxiety and stress, as well as providing pivotal support for autonomic function in the peripheral nervous system. As such, abnormal function of NA 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. The wide variation in clinical features associated with these disorders is paralleled by mounting evidence that unique subpopulations of NA neurons are selectively affected. Heterogeneity among NA neurons is further illustrated by their different anatomical location, cell morphology, axonal projection pattern, neuropeptide expression and vulnerability to environmental factors. Mechanisms that determine these differences are unknown and presently no molecular markers have been identified which are capable of distinguishing individual NA neuron subtypes. Understanding how heterogeneity arises within the NA system is a key step in determining the mechanism of selective neuronal dysfunction following genetic or environmental insult and to gaining genetic access to particular NA neuron subpopulations for experimental study. To fill this knowledge gap, we are developing a set of novel genetic tools to study the development and function of the NA system in vivo. These tools will provide, for the first time, a means to gain genetic access to subsets of NA neurons and the ability to determine the effect of altered NA signaling during critical periods of development on circuits underlying behaviors such as attention and learning &memory.