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.

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Plummer, Nicholas W; Ungewitter, Erica K; Smith, Kathleen G et al. (2017) A new mouse line for cell ablation by diphtheria toxin subunit A controlled by a Cre-dependent FLEx switch. Genesis 55:
Plummer, Nicholas W; Scappini, Erica L; Smith, Kathleen G et al. (2017) Two Subpopulations of Noradrenergic Neurons in the Locus Coeruleus Complex Distinguished by Expression of the Dorsal Neural Tube Marker Pax7. Front Neuroanat 11:60
Plummer, Nicholas W; de Marchena, Jacqueline; Jensen, Patricia (2016) A knock-in allele of En1 expressing dre recombinase. Genesis 54:447-54
Damborsky, Joanne C; Smith, Kathleen G; Jensen, Patricia et al. (2016) Local cholinergic-GABAergic circuitry within the basal forebrain is modulated by galanin. Brain Struct Funct :
Robertson, Sabrina D; Plummer, Nicholas W; Jensen, Patricia (2016) Uncovering diversity in the development of central noradrenergic neurons and their efferents. Brain Res 1641:234-44
Sciolino, Natale R; Plummer, Nicholas W; Chen, Yu-Wei et al. (2016) Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types. Cell Rep 15:2563-73
Plummer, Nicholas W; Evsyukova, Irina Y; Robertson, Sabrina D et al. (2015) Expanding the power of recombinase-based labeling to uncover cellular diversity. Development 142:4385-93
Robertson, Sabrina D; Plummer, Nicholas W; de Marchena, Jacqueline et al. (2013) Developmental origins of central norepinephrine neuron diversity. Nat Neurosci 16:1016-23
Bang, Sun Jung; Jensen, Patricia; Dymecki, Susan M et al. (2012) Projections and interconnections of genetically defined serotonin neurons in mice. Eur J Neurosci 35:85-96