Fos immunoreactivity in hypocretin-synthesizing and hypocretin-1 receptor-expressing neurons:: Effects of diurnal and nocturnal spontaneous waking, stress and hypocretin-1 administration
Fos immunoreactivity in hypocretin-synthesizing and hypocretin-1 receptor-expressing neurons:: Effects of diurnal and nocturnal spontaneous waking, stress and hypocretin-1 administration
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DOI：
10.1016/s0306-4522(03)00334-8
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Berridge, CW
中科院分区：
文献类型：
--
作者：
España, RA;Valentino, RJ;Berridge, CW
下丘脑素/食欲素通过跨多个终端区的作用调节睡眠-觉醒状态。在清醒状态下，下丘脑泌素也可能参与高唤醒过程，包括与压力相关的过程。目前的研究考察了在不同的行为状态/环境条件下，与不同水平的觉醒和觉醒相关的不同行为状态/环境条件下，下丘脑-内分泌素合成神经元和下丘脑-1受体表达神经元内神经元活动(通过Fos免疫反应测量)发生变化的程度。用双标记免疫组织化学方法显示下丘脑外侧区的Fos和前原下丘脑或蓝斑的下丘脑下丘脑-1受体，并选择参与行为状态/觉醒调节的基底前脑区域。动物在以下条件下被测试：1)昼夜睡眠；2)昼夜自发觉醒；3)夜间自发清醒；4)高唤醒(昼夜新奇压力)。此外，还检测了给予下丘脑肌素-1(0.07和0.7nmol)对这两个神经元群体内Fos水平的影响。清醒时间，根据灌流前90分钟的评分，在白天自发唤醒、夜间自发唤醒和高唤醒中基本相似。与白天睡眠相比，夜间自发觉醒和高唤醒，而不是昼夜自发唤醒，与下丘脑泌素合成神经元内Fos水平的增加有关。在表达下丘脑-1受体的神经元中，只有高觉醒状态才与Fos水平升高有关。给药剂量依赖地增加表达下丘脑-1受体的神经元内Fos的水平，达到相当于或超过在高觉醒状态下观察到的水平。总而言之，这些观察结果支持了下丘脑克汀神经元活动在昼夜节律周期中变化的假设。此外，这些数据表明，清醒本身可能与下丘脑神经传递增加无关。相比之下，包括压力在内的高唤醒状态似乎与显著更高的下丘脑神经传递率相关。最后，这些研究提供了进一步的证据表明，在这个肽系统的行为状态调节作用中，下丘脑素跨各种与唤醒相关的基底前脑和脑干区域的协调作用。(C)2003年IBRO。爱思唯尔有限公司出版。保留所有权利。
Hypocretin/orexin modulates sleep-wake state via actions across multiple terminal fields. Within waking, hypocretin may also participate in high-arousal processes, including those associated with stress. The current studies examined the extent to which alterations in neuronal activity, as measured by Fos immunoreactivity, occur within both hypocretin-synthesizing and hypocretin-1 receptor-expressing neurons across varying behavioral state/environmental conditions associated with varying levels of waking and arousal. Double-label immunohistochemistry was used to visualize Fos and either prepro-hypocretin in the lateral hypothalamus or hypocretin-1 receptors in the locus coeruleus and select basal forebrain regions involved in the regulation of behavioral state/arousal. Animals were tested under the following conditions: 1) diurnal sleeping; 2) diurnal spontaneous waking; 3) nocturnal spontaneous waking; and 4) high-arousal waking (diurnal novelty-stress). Additionally, the effects of hypocretin-1 administration (0.07 and 0.7 nmol) on levels of Fos were examined within these two neuronal populations. Time spent awake, scored for the 90-min preceding perfusion, was largely comparable in diurnal spontaneous waking, nocturnal spontaneous waking and high-arousal waking. Nocturnal spontaneous waking and high-arousal waking, but not diurnal spontaneous waking, were associated with increased levels of Fos within hypocretin-synthesizing neurons, relative to diurnal sleeping. Within hypocretin-1 receptor-expressing neurons, only high-arousal waking was associated with increased levels of Fos. Hypocretin-1 administration dose-dependently increased levels of Fos within hypocretin-1 receptor-expressing neurons to levels comparable to, or exceeding, levels observed in high-arousal waking. Combined, these observations support the hypothesis that hypocretin neuronal activity varies across the circadian cycle. Additionally, these data suggest that waking per se may not be associated with increased hypocretin neurotransmission. In contrast, high-arousal states, including stress, appear to be associated with substantially higher rates of hypocretin neurotransmission. Finally, these studies provide further evidence indicating coordinated actions of hypocretin across a variety of arousal-related basal forebrain and brainstem regions in the behavioral state modulatory actions of this peptide system. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.