Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus
Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus
复制标题
DOI：
10.1523/jneurosci.21-23-09273.2001
复制
发表时间：
2001-12-01
影响因子：
5.3
通讯作者：
Haas, HL
中科院分区：
文献类型：
--
作者：
Eriksson, KS;Sergeeva, O;Haas, HL
下丘脑增食欲素神经肽与睡眠和进食的调节有关，食欲素能神经传递障碍导致发作性睡病的表型。组胺也被证明在调节睡眠和进食方面发挥作用。因此，我们用电生理学、免疫细胞化学和逆转录-聚合酶链式反应的方法研究了中枢神经系统中食欲素和组胺系统的关系。食欲素-A和食欲素B都通过作用于突触后受体，使组胺能结节乳头神经元去极化并增加其放电频率。去极化与输入电阻的小幅下降有关，可能是由电生Na+/Ca~(2+)交换器和Ca~(2+)电流激活所致。在一项针对这两种食欲素受体的单细胞RT-PCR研究中，我们发现大多数结节乳头神经元都表达这两种受体，并且食欲素-2受体的表达强于食欲素-1受体。免疫细胞化学研究表明，组胺和增食欲素神经元通常位于彼此很近的地方。这两种类型的神经元之间的联系似乎是相互的，因为增食欲素神经元主要由组胺能轴突支配。这些结果表明，这两组下丘脑神经元之间存在功能联系，它们可能在调节快速眼动、睡眠和进食方面进行合作。
The hypothalamic orexin (hypocretin) neuropeptides are associated with the regulation of sleep and feeding, and disturbances in orexinergic neurotransmission lead to a narcoleptic phenotype. Histamine has also been shown to play a role in the regulation of sleep and feeding. Therefore, we studied the relationship between the orexin and histamine systems of the CNS using electrophysiology, immunocytochemistry, and the reverse transcriptase (RT)-PCR method.Both orexin-A and orexin-B depolarized the histaminergic tuberomammillary neurons and increased their firing rate via an action on postsynaptic receptors. The depolarization was associated with a small decrease in input resistance and was likely caused by activation of both the electrogenic Na+/Ca2+ exchanger and a Ca2+ current. In a single-cell RT-PCR study using primers for the two orexin receptors, we found that most tuberomammillary neurons express both receptors and that the expression of the orexin-2 receptor is stronger than that of the orexin-1 receptor. Immunocytochemical studies show that the histamine and orexin neurons are often located very close to each other. The contacts between these two types of neurons seem to be reciprocal, because the orexin neurons are heavily innervated by histaminergic axons. These results suggest a functional connection between the two populations of hypothalamic neurons and that they may cooperate in the regulation of rapid-eye-movement sleep and feeding.