Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons
Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons
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DOI：
10.1523/jneurosci.2835-17.2018
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发表时间：
2018-07-11
影响因子：
5.3
通讯作者：
Sakurai, Takeshi
中科院分区：
文献类型：
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作者：
Saito, Yuki C.;Maejima, Takashi;Sakurai, Takeshi
下丘脑在睡眠/觉醒状态的调节中起着重要作用。虽然腹外侧视前核（VLPO）在睡眠的启动和维持中起着关键作用，但下丘脑的外侧后部含有与觉醒维持有关的神经元群，包括下丘脑外侧区（LHA）中的食欲素产生神经元（食欲素神经元）和结节乳头核（TMN）中的组胺能神经元。在寻找与雄性小鼠TMN中的组氨酸脱羧酶阳性（HDC+）、组胺能神经元（HDC神经元）和LHA中的食欲素神经元直接突触接触的神经元的过程中，我们发现这些觉醒相关神经元受到包括VLPO在内的视前区中的GABA能神经元的严重支配。进一步研究了与下丘脑唤醒相关神经元直接突触联系的VLPO中GABA能神经元（GABA（VLPO）神经元）的电生理特征。这些神经元（GABA（VLPO -> HDC）或GABA（VLPO -> orexin）神经元）均能被去甲肾上腺素和5-羟色胺强烈抑制，表现出VLPO内睡眠促进神经元的典型电生理特征。这项工作提供了直接的证据GABA（VLPO）神经元和下丘脑唤醒神经元之间的单突触连接，并确定这些神经元通路的单胺的影响。
The hypothalamus plays an important role in the regulation of sleep/wakefulness states. While the ventrolateral preoptic nucleus (VLPO) plays a critical role in the initiation and maintenance of sleep, the lateral posterior part of the hypothalamus contains neuronal populations implicated in maintenance of arousal, including orexin-producing neurons (orexin neurons) in the lateral hypothalamic area (LHA) and histaminergic neurons in the tuberomammillary nucleus (TMN). During a search for neurons that make direct synaptic contact with histidine decarboxylase-positive (HDC+), histaminergic neurons (HDC neurons) in the TMN and orexin neurons in the LHA of male mice, we found that these arousal-related neurons are heavily innervated by GABAergic neurons in the preoptic area including the VLPO. Wefurther characterized GABAergic neurons electrophysiologically in the VLPO (GABA(VLPO) neurons) that make direct synaptic contact with these hypothalamic arousal-related neurons. These neurons (GABA(VLPO -> HDC) or GABA(VLPO -> orexin) neurons) were both potently inhibited by noradrenaline and serotonin, showing typical electrophysiological characteristics of sleep-promoting neurons in the VLPO. This work provides direct evidence of monosynaptic connectivity between GABA(VLPO) neurons and hypothalamic arousal neurons and identifies the effects of monoamines on these neuronal pathways.