Central Noradrenergic Neuron Subtype Development and Function

去甲肾上腺素(NE)神经元是神经系统中主动合成去甲肾上腺素的细胞，在控制注意力、情绪、食欲、记忆、焦虑和压力的回路中发挥着重要作用。此外，去甲肾上腺素神经元为周围神经系统的自主功能提供关键的支持。因此，NE神经元的功能异常与多种神经系统疾病有关，如抑郁症、创伤后应激障碍(PTSD)、注意缺陷多动障碍(ADHD)、帕金森病、阿尔茨海默病和唐氏综合征。在其中几种疾病中，有证据表明，NE神经元的独特亚群受到选择性影响。NE神经元的解剖位置、细胞形态、轴突投射模式、神经肽表达和对环境因素的易感性说明了NE神经元之间的进一步异质性。决定这些特征的机制目前尚不清楚，也没有能够区分生理上相关的NE神经元亚型的分子标记被识别。这些知识对于理解为什么精选的NE神经元亚群对疾病和环境侮辱具有不同的易感性是至关重要的。为了开始填补这一知识空白，我们正在通过应用一组新的基于重组酶的遗传工具来研究小鼠中枢神经系统中遗传定义的NE神经元亚群的起源、发育和功能。

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 heterogeneity 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.