Neurochemical Heterogeneity Among Lateral Hypothalamic Hypocretin/Orexin and Melanin-Concentrating Hormone Neurons Identified Through Single-Cell Gene Expression Analysis.
Neurochemical Heterogeneity Among Lateral Hypothalamic Hypocretin/Orexin and Melanin-Concentrating Hormone Neurons Identified Through Single-Cell Gene Expression Analysis.
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DOI：
10.1523/eneuro.0013-17.2017
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发表时间：
2017-09
期刊：
影响因子：
3.4
通讯作者：
Jackson AC
中科院分区：
文献类型：
--
作者：
Mickelsen LE;Kolling FW 4th;Chimileski BR;Fujita A;Norris C;Chen K;Nelson CE;Jackson AC
下丘脑外侧区（LHA）位于多个神经和体液系统的交叉点，并协调行为的基本方面。在LHA中发现的两种神经元细胞类型通过它们的下丘脑泌素/食欲素（Hcrt/Ox）和黑色素浓缩激素（MCH）的表达来定义，并且都是唤醒、进食和代谢的重要调节剂。证据表明，这些细胞群具有比以前认识到的更复杂的信号库，特别是在它们的其他神经肽的共表达和GABA和谷氨酸的合成和释放机制方面。在这里，我们进行了单细胞表达谱的方法来破译的神经化学表型，其中的异质性，Hcrt/Ox和MCH神经元。在转基因小鼠品系中，我们使用单细胞定量聚合酶链反应（qPCR）来量化48个关键基因的表达，这些基因包括神经肽、快速神经递质成分和其他关键标记物，这揭示了意想不到的神经化学多样性。我们发现，单个MCH和Hcrt/Ox神经元表达多种神经肽和兴奋性和抑制性快速神经传递的标记物的转录本。几乎所有的MCH和大约一半的Hcrt/Ox神经元采样表达谷氨酸释放和GABA合成的情况下，囊泡GABA释放途径的机器。此外，我们发现，这种配置文件是一个亚群的LHA谷氨酸能神经元的特征，但与广泛的LHA GABA能神经元的人口。识别Hcrt/Ox和MCH神经元的神经化学多样性将进一步了解这些群体如何通过多种信号传导机制调节突触后兴奋性并协调不同的行为输出。
The lateral hypothalamic area (LHA) lies at the intersection of multiple neural and humoral systems and orchestrates fundamental aspects of behavior. Two neuronal cell types found in the LHA are defined by their expression of hypocretin/orexin (Hcrt/Ox) and melanin-concentrating hormone (MCH) and are both important regulators of arousal, feeding, and metabolism. Conflicting evidence suggests that these cell populations have a more complex signaling repertoire than previously appreciated, particularly in regard to their coexpression of other neuropeptides and the machinery for the synthesis and release of GABA and glutamate. Here, we undertook a single-cell expression profiling approach to decipher the neurochemical phenotype, and heterogeneity therein, of Hcrt/Ox and MCH neurons. In transgenic mouse lines, we used single-cell quantitative polymerase chain reaction (qPCR) to quantify the expression of 48 key genes, which include neuropeptides, fast neurotransmitter components, and other key markers, which revealed unexpected neurochemical diversity. We found that single MCH and Hcrt/Ox neurons express transcripts for multiple neuropeptides and markers of both excitatory and inhibitory fast neurotransmission. Virtually all MCH and approximately half of the Hcrt/Ox neurons sampled express both the machinery for glutamate release and GABA synthesis in the absence of a vesicular GABA release pathway. Furthermore, we found that this profile is characteristic of a subpopulation of LHA glutamatergic neurons but contrasts with a broad population of LHA GABAergic neurons. Identifying the neurochemical diversity of Hcrt/Ox and MCH neurons will further our understanding of how these populations modulate postsynaptic excitability through multiple signaling mechanisms and coordinate diverse behavioral outputs.