Central Noradrenergic Neuron Subtype Development and Function

National Institute Of Environmental Health Sciences

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Abstract

The prefrontal cortex (PFC), the region of the frontal lobe that is involved in cognitive functions, receives a relatively rich innervation of noradrenergic fibers originating from the locus coeruleus. It is thought that noradrenergic signaling in the PFC modulates cognitive functions. Indeed, altered noradrenergic signaling is implicated in the cognitive dysfunction associated with a number of disorders including Rett syndrome, attention-deficit/hyperactivity disorder (ADHD), Parkinsons and Alzheimers disease. To date, much of our understanding about the subpopulation(s) of noradrenergic neurons that project to and modulate PFC circuits comes from non-genetic tract tracing and lesioning studies in postnatal animals. Little is known about the molecular identity of these subpopulations or how altered noradrenergic signaling during embryonic development affects normal brain structure and function because tools with the needed resolution to visualize and manipulate different noradrenergic subtypes during development simply have not existed. To fill this knowledge gap, we are developing a set of recombinase-based genetic tools to permit selective visualization and manipulation of molecularly defined subsets of noradrenergic neurons in the mouse. These tools will provide, for the first time, a means to gain genetic access to subsets of noradrenergic neurons during embryonic development and the ability to determine how genetic and environmental alterations in noradrenergic signaling during development results in disrupted PFC function.