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.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$1,646,527
Indirect Cost
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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
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; 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
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