GABAergic neurons in the preoptic area send direct inhibitory projections to orexin neurons.
GABAergic neurons in the preoptic area send direct inhibitory projections to orexin neurons.
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DOI：
10.3389/fncir.2013.00192
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发表时间：
2013
影响因子：
3.5
通讯作者：
Sakurai T
中科院分区：
文献类型：
--
作者：
Saito YC;Tsujino N;Hasegawa E;Akashi K;Abe M;Mieda M;Sakimura K;Sakurai T
下丘脑视前区(POA)的神经元群体在睡眠时迅速放电，表现出睡眠/清醒状态依赖的放电模式，这与在觉醒系统中观察到的模式相反。这些视前“睡眠活跃”神经元中的大多数含有抑制性神经递质GABA。另一方面，下丘脑外侧区(LHA)的大量神经元含有食欲素，食欲素在维持觉醒过程中发挥重要作用，并对觉醒相关神经元产生兴奋影响。了解POA睡眠活跃神经元和食欲素神经元之间的解剖和功能相互作用是很重要的，这两个神经元在调节睡眠/觉醒状态方面都发挥着重要但相反的作用。在这项研究中，我们证实了对POA中GABA能神经元的特定药物遗传刺激导致了非快速眼动(NREM)睡眠的增加。接下来，我们使用通道视紫红质2(ChR2)作为顺行示踪剂和光遗传工具，研究了POA GABA能神经元和食欲素神经元之间的直接连接。我们通过AAV介导的基因转移在POA的GABA能神经元中选择性地表达了ChR2-EYFP，并检测了表达ChR2-EYFP的轴突的投射部位，以及光遗传刺激ChR2-EYFP对增食欲素神经元活性的影响。我们发现，这些神经元向下丘脑和脑干中与觉醒相关的区域发送广泛的投射，包括LHA，在那里这些纤维与食欲素神经元密切对应。对这些纤维的光发生刺激导致食欲素神经元的快速抑制。这些观察结果提示POA GABA能神经元和食欲素神经元之间存在直接联系。
Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly during sleep, exhibiting sleep/waking state-dependent firing patterns that are the reciprocal of those observed in the arousal system. The majority of these preoptic “sleep-active” neurons contain the inhibitory neurotransmitter GABA. On the other hand, a population of neurons in the lateral hypothalamic area (LHA) contains orexins, which play an important role in the maintenance of wakefulness, and exhibit an excitatory influence on arousal-related neurons. It is important to know the anatomical and functional interactions between the POA sleep-active neurons and orexin neurons, both of which play important, but opposite roles in regulation of sleep/wakefulness states. In this study, we confirmed that specific pharmacogenetic stimulation of GABAergic neurons in the POA leads to an increase in the amount of non-rapid eye movement (NREM) sleep. We next examined direct connectivity between POA GABAergic neurons and orexin neurons using channelrhodopsin 2 (ChR2) as an anterograde tracer as well as an optogenetic tool. We expressed ChR2-eYFP selectively in GABAergic neurons in the POA by AAV-mediated gene transfer, and examined the projection sites of ChR2-eYFP-expressing axons, and the effect of optogenetic stimulation of ChR2-eYFP on the activity of orexin neurons. We found that these neurons send widespread projections to wakefulness-related areas in the hypothalamus and brain stem, including the LHA where these fibers make close appositions to orexin neurons. Optogenetic stimulation of these fibers resulted in rapid inhibition of orexin neurons. These observations suggest direct connectivity between POA GABAergic neurons and orexin neurons.
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DOI：
10.1073/pnas.0700293104
发表时间：
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影响因子：
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作者：
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影响因子：
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作者：
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