Histaminergic descending inputs to the mesopontine tegmentum and their role in the control of cortical activation and wakefulness in the cat
Histaminergic descending inputs to the mesopontine tegmentum and their role in the control of cortical activation and wakefulness in the cat
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DOI：
10.1523/jneurosci.16-04-01523.1996
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发表时间：
1996-02
期刊：
影响因子：
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通讯作者：
Jian-Sheng Lin;Yiping Hou;K. Sakai;M. Jouvet
中科院分区：
文献类型：
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作者：
Jian-Sheng Lin;Yiping Hou;K. Sakai;M. Jouvet
我们以前已经证明了组胺能神经元在唤醒机制中的重要性。除了它们的上行轴突，这些神经元还向中脑脑桥被盖（MPT）发送大量下行输入，MPT在清醒期间的皮质激活中起关键作用（W）。这种解剖学上的联系表明，组胺能控制的机制，MPT相关的行为状态。在这项研究中，我们试图证明，在光学显微镜水平，下丘脑被盖组胺能通路和他们的地形相互作用与MPT神经元的猫，并进一步探讨他们参与睡眠-觉醒控制。用组胺（HA）免疫组织化学方法，在MPT内，包括被盖背外侧核、蓝斑（LC）、LC α和LC α周围，检测到大量非常细小、短而曲张的HA阳性纤维和终末样点。此外，这些纤维和终末样结构被发现在接近大量的胆碱能或去甲肾上腺素能神经元。我们还研究了微量给药的HA激动剂和拮抗剂到脑桥被盖的大脑皮层脑电图（EEG）功率谱和自由活动的猫的睡眠-觉醒周期的影响。微量注射HA或2-thiazolylethylamine（一种H1受体激动剂）可引起皮质慢活动的长期抑制和安静觉醒的增加（W）。然而，副作用睡眠受到的影响较小。HA的影响被衰减全身或原位预处理与美托洛尔（H1受体拮抗剂），单独注射时产生的增加慢波睡眠。在同一区域微量注射Impromidine（一种H2受体激动剂）对皮层EEG或W均无影响。由于MPT上行和假定的胆碱能神经元在W的皮质激活期间紧张性放电，并且由于HA通过H1受体引起MPT胆碱能神经元的兴奋，我们假设MPT中的组胺能下行传入将促进皮质去兴奋化和W，至少部分地，通过激活位于胆碱能神经元上的H1受体，组胺能神经元和胆碱能神经元之间的相互作用构成了在W期间皮层激活中重要回路。
We have demonstrated previously the importance of histaminergic neurons in arousal mechanisms. In addition to their ascending axons, these neurons also send heavy descending inputs to the mesopontine tegmentum (MPT), which plays a key role in cortical activation during wakefulness (W). This anatomical link suggests histaminergic control of the mechanisms of the MPT relevant to behavioral states. In this study, we sought to demonstrate, at the light microscopy level, hypothalamotegmental histaminergic pathways and their topographical interaction with MPT neurons in the cat and to explore further their involvement in sleep-wake control. Using immunohistochemistry of histamine (HA), either alone or together with that of choline- acetyltransferase or tyrosine hydroxylase, a large number of very fine, short and varicose HA-positive fibers and terminal-like dots were detected in the MPT, including the laterodorsal tegmental nucleus, locus coeruleus (LC), LC alpha, and peri-LC alpha. Furthermore, these fibers and terminal-like structures were found in close proximity to a great number of cholinergic or noradrenergic neurons. We also investigated the effects of microadministration of HA agonists and antagonist into the mediodorsal pontine tegmentum on the cortical electroencephalogram (EEG) power spectra and the sleep-wake cycle in freely moving cats. Microinjection of HA or 2-thiazolylethylamine (an H1-receptor agonist) caused a long-lasting suppression of cortical slow activity and an increase in quiet wakefulness (W). Paradoxical sleep, however, was less affected. The effects of HA were attenuated by systemic or in situ pretreatment with mepyramine (an H1-receptor antagonist), which when injected alone produced an increase in slow wave sleep. Microinjection of impromidine (an H2-receptor agonist) into the same area had no effect on either the cortical EEG or W. Because MPT ascending and presumed cholinergic neurons discharge tonically during cortical activation of W and because HA causes excitation of MPT cholinergic neurons via H1 receptors, we hypothesize that the histaminergic descending afferents in the MPT would promote cortical desynchronization and W, at least partially, via activation of H1 receptors situated on cholinergic neurons and that the interactions between histaminergic and cholinergic neurons constitute an important circuit in cortical activation during W.