Developmental origins of central norepinephrine neuron diversity.

Developmental origins of central norepinephrine neuron diversity.
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DOI:
10.1038/nn.3458
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发表时间:
2013-08
影响因子:
25
通讯作者:
Jensen, Patricia
Jensen, Patricia
中科院分区:
医学1区
文献类型:
--
作者:
Robertson, Sabrina D.;Plummer, Nicholas W.;de Marchena, Jacqueline;Jensen, Patricia

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产生中枢去甲肾上腺素的神经元由不同的细胞群组成,这些细胞在解剖位置、连接性、功能以及对疾病和环境损害的反应方面有所不同。目前,产生这种多样性的机制尚不清楚。在这里,我们阐明了发育中的小鼠后脑中分子上不同的祖细胞群与成熟的去甲肾上腺素神经元亚型身份之间的线性关系。我们已经鉴定出成熟去甲肾上腺素神经元的四个遗传上可分离的亚群,其解剖位置、轴突形态和传出投射模式不同。其中一个亚群显示出对前额皮质的意外投射,挑战了长期以来的信念,即蓝斑(LoC)是去甲肾上腺素投射到皮质的唯一来源。这些发现揭示了中枢去甲肾上腺素神经元的胚胎起源,并首次为未来研究复杂行为和生理过程(包括唤醒、注意力、情绪、记忆、食欲和体内平衡)中的个体去甲肾上腺素回路提供了多个分子切入点。
Central norepinephrine producing neurons comprise a diverse population of cells differing in anatomical location, connectivity, function and response to disease and environmental insult. At present, the mechanisms that generate this diversity are unknown. Here we elucidate the lineal relationship between molecularly distinct progenitor populations in the developing mouse hindbrain and mature norepinephrine neuron subtype identity. We have identified four genetically separable subpopulations of mature norepinephrine neurons differing in their anatomical location, axon morphology and efferent projection pattern. One of the subpopulations revealed an unexpected projection to the prefrontal cortex, challenging the long-held belief that the locus coeruleus (LoC) is the sole source of norepinephrine projections to the cortex. These findings reveal the embryonic origins of central norepinephrine neurons and provide for the first time multiple molecular points of entry for future study of individual norepinephrine circuits in complex behavioral and physiological processes including arousal, attention, mood, memory, appetite, and homeostasis.
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