Effects of hypocretin2-saporin and antidopamine-β-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone
Effects of hypocretin2-saporin and antidopamine-β-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone
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DOI：
10.1111/j.0953-816x.2004.03366.x
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发表时间：
2004-05-01
影响因子：
3.4
通讯作者：
Shiromani, PJ
中科院分区：
文献类型：
--
作者：
Blanco-Centurion, C;Gerashchenko, D;Shiromani, PJ
下丘脑分泌素神经元与调节睡眠-觉醒状态有关，因为它们在患有睡眠障碍性嗜睡症的患者中缺失。下丘脑分泌素（HCRT）神经元仅位于下丘脑后部的皮层周围区域和大量支配脑桥神经的脑干神经元，如蓝斑（LC），传统上认为蓝斑与促进觉醒有关。目前尚不清楚脑桥的下丘脑分泌素神经支配如何调节睡眠-觉醒状态，因为脑桥损伤从未被证明会增加睡眠。在以前的研究中，很可能特定的神经元没有受损。因此，在本研究中，我们将基于皂苷的神经毒素应用于大鼠的脑桥背外侧并监测睡眠。抗多巴胺- β -羟酶-皂苷杀死了LC神经元，但睡眠仅在两小时的明暗过渡期间受到影响。下丘脑分泌素-皂苷的应用相对于其他邻近神经元杀死较少的LC神经元。这是因为LC神经元拥有下丘脑分泌素受体1，但与该受体结合的配体下丘脑分泌素2与下丘脑分泌素受体2的亲和力较低。与对照组相比，下丘脑分泌素-皂苷损伤的大鼠在黑暗期睡眠增加，在快速眼动睡眠期间肢体运动增加。所有受损大鼠均无睡眠性快速眼动睡眠期或猝倒。我们的结论是，下丘脑分泌素支配的脑桥神经在关灯时唤醒动物（通过其支配的LC神经），在夜间其余时间维持唤醒和抑制睡眠（通过其他脑桥神经元的更广泛的神经支配），并调节肌肉张力。
The hypocretin neurons have been implicated in regulating sleep-wake states as they are lost in patients with the sleep disorder narcolepsy. Hypocretin (HCRT) neurons are located only in the perifornical region of the posterior hypothalamus and heavily innervate pontine brainstem neurons, such as the locus coeruleus (LC), which have traditionally been implicated in promoting arousal. It is not known how the hypocretin innervation of the pons regulates sleep-wake states as pontine lesions have never been shown to increase sleep. It is likely that in previous studies specific neurons were not lesioned. Therefore, in this study, we applied saporin-based neurotoxins to the dorsolateral pons and monitored sleep in rats. Anti-dopamine-beta-hydroxylase-saporin killed the LC neurons but sleep was affected only during a two hour light-dark transition period. Application of hypocretin2-saporin killed fewer LC neurons relative to other adjacent neurons. This occurred because the LC neurons possess the hypocretin receptor 1 but the ligand hypocretin 2 binds to this receptor with less affinity relative to the hypocretin receptor 2. The hypocretin2-saporin lesioned rats compared to controls had increased sleep during the dark period and displayed increased limb movements during REM sleep. None of the lesioned rats had sleep onset REM sleep periods or cataplexy. We conclude that the hypocretin innervation to the pons functions to awaken the animal when the lights turn off (via its innervation of the LC), sustains arousal and represses sleep during the rest of the night (via a wider innervation of other pontine neurons), and modulates muscle tone.