Central Noradrenergic Neuron Subtype Development and Function

去甲肾上腺素（NA）神经元是神经系统中主动合成去甲肾上腺素的细胞，在涉及注意力、情绪、食欲、记忆、焦虑和压力的神经回路中起重要作用，并为周围神经系统的自主神经功能提供关键支持。因此，NA神经元的异常功能与广泛的神经系统疾病有关，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症。与这些疾病相关的临床特征的广泛变化与越来越多的证据相一致，即NA神经元的独特亚群受到选择性影响。NA神经元的异质性进一步体现在它们不同的解剖位置、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上。决定这些差异的机制尚不清楚，目前还没有确定能够区分单个NA神经元亚型的分子标记。了解NA系统内异质性是如何产生的，是确定遗传或环境损伤后选择性神经元功能障碍机制的关键一步，也是获得特定NA神经元亚群的遗传途径进行实验研究的关键一步。

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.