The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus
The endogenous somnogen adenosine excites a subset of sleep-promoting neurons via A2A receptors in the ventrolateral preoptic nucleus
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DOI：
10.1016/j.neuroscience.2005.05.045
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Fort, P
中科院分区：
文献类型：
--
作者：
Gallopin, T;Luppi, PH;Fort, P
最近的研究表明，腹外侧视前核中的神经元通过抑制促醒系统对睡眠至关重要，但在睡眠开始时触发其激活的过程仍有待建立。腺苷是一种内源性的睡眠促进物质，有证据表明腺苷诱导的睡眠需要激活脑内A（2A）受体，因此我们在大鼠脑片上验证了腺苷通过A（2A）受体激活腹外侧视前核睡眠神经元的假说。从我们最初的体外鉴定这些神经元均匀抑制去甲肾上腺素和乙酰胆碱唤醒递质，我们建立了腹外侧视前核包括两个混合亚型的睡眠神经元，不同的在他们的发射反应5-羟色胺，诱导抑制（1型细胞）或兴奋（2型细胞）。由于两种细胞类型都含有甘丙肽并表达谷氨酸脱羧酶-65/67 mRNA，因此它们可能对应于抑制唤醒系统的睡眠促进神经元。我们使用A（1）和A（2A）腺苷受体激动剂和拮抗剂的药理学研究进一步揭示，只有2型神经元通过A（2A）腺苷受体的突触后激活被腺苷兴奋。因此，本研究是腺苷直接激活睡眠神经元的第一个证明。我们的研究结果进一步支持睡眠神经元的细胞和功能异质性，这可能使它们对睡眠调节的差异贡献成为可能。腺苷和5-羟色胺在觉醒过程中逐渐积累。我们提出，2型神经元，这对这些稳态信号的反应，增加他们的发射参与睡眠诱导。相比之下，1型神经元可能在巩固睡眠中发挥作用。(c)2005年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Recent research has shown that neurons in the ventrolateral preoptic nucleus are crucial for sleep by inhibiting wake-promoting systems, but the process that triggers their activation at sleep onset remains to be established. Since evidence indicates that sleep induced by adenosine, an endogenous sleep-promoting substance, requires activation of brain A(2A) receptors, we examined the hypothesis that adenosine could activate ventrolateral preoptic nucleus sleep neurons via A(2A) adenosine receptors in rat brain slices. Following on from our initial in vitro identification of these neurons as uniformly inhibited by noradrenaline and acetylcholine arousal transmitters, we established that the ventrolateral preoptic nucleus comprises two intermingled subtypes of sleep neurons, differing in their firing responses to serotonin, inducing either an inhibition (Type-1 cells) or an excitation (Type-2 cells). Since both cell types contained galanin and expressed glutamic acid decarboxylase-65/67 mRNAs, they potentially correspond to the sleep promoting neurons inhibiting arousal systems. Our pharmacological investigations using A(1) and A(2A) adenosine receptors agonists and antagonists further revealed that only Type-2 neurons were excited by adenosine via a postsynaptic activation of A(2A) adenosine receptors. Hence, the present study is the first demonstration of a direct activation of the sleep neurons by adenosine. Our results further support the cellular and functional heterogeneity of the sleep neurons, which could enable their differential contribution to the regulation of sleep. Adenosine and serotonin progressively accumulate during arousal. We propose that Type-2 neurons, which respond to these homeostatic signals by increasing their firing are involved in sleep induction. In contrast, Type-1 neurons would likely play a role in the consolidation of sleep. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.