GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep.
GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep.
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DOI：
10.1111/j.1460-9568.2010.07295.x
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Jones BE
中科院分区：
文献类型：
--
作者：
Hassani OK;Henny P;Lee MG;Jones BE
外侧下丘脑（LH），其中唤醒活性含食欲素（Orx）的神经元位于，已被认为是觉醒中心。然而，含有黑色素浓缩激素（MCH）的神经元与Orx神经元共同分布在其中，与它们相反，在睡眠期间活跃，而不是清醒。在本研究中，采用神经生物素（Nb）在自然睡眠-清醒的头部固定大鼠神经元的细胞记录和标记，我们确定了另一个人口的混合睡眠活跃的细胞，不含MCH（或Orx），但利用GABA作为神经递质。"睡眠最大"活跃神经元代表了LH中记录的Nb标记的MCH（和Orx）免疫阴性（-）细胞的53%。为了鉴定它们的神经递质，在与Nb标记的索马相邻的切片中寻找Nb标记的/MCH −神经元的Nb标记的静脉曲张，并对GABA（VGAT）或谷氨酸（VGluT2）的囊泡转运蛋白进行免疫染色。一小部分睡眠最大Nb +/MCH −神经元（19%）在慢波睡眠（SWS，称为"S-max"）期间放电最大，与δ EEG活动呈正相关，并且从Nb标记静脉曲张的VGAT染色来看，似乎是GABA能的。绝大部分睡眠最大Nb +/MCH −神经元（81%）在异相睡眠（PS，称为"P-max"）期间最大程度地放电，与EMG振幅呈负相关，并且来自Nb标记的静脉曲张，也似乎主要是GABA能。考虑到它们在睡眠-觉醒周期中的放电曲线，P-max和S-max GABA能神经元可以抑制唤醒系统的其他神经元，包括LH中的局部Orx神经元。因此，它们可以通过肌肉张力来抑制觉醒，促进睡眠，包括肌肉张力不足的PS。
The lateral hypothalamus (LH), where wake-active Orexin (Orx)-containing neurons are located, has been considered a waking center. Yet, melanin-concentrating hormone (MCH)-containing neurons are codistributed therein with Orx neurons and in contrast to them, are active during sleep, not waking. In the present study employing juxtacellular recording and labeling of neurons with Neurobiotin (Nb) in naturally sleeping-waking head-fixed rats, we identified another population of intermingled sleep-active cells, which do not contain MCH (or Orx) but utilize GABA as a neurotransmitter. The “sleep-max” active neurons represented 53% of Nb-labeled MCH (and Orx) immunonegative (−) cells recorded in the LH. For identification of their neurotransmitter, Nb-labeled varicosities of the Nb-labeled/MCH− neurons were sought within sections adjacent to the Nb-labeled soma and immunostained for the vesicular transporter for GABA (VGAT) or for glutamate (VGluT2). A small proportion of sleep-max Nb+/MCH− neurons (19%) discharged maximally during slow wave sleep (SWS, called “S-max”) in positive correlation with delta EEG activity and from VGAT staining of Nb-labeled varicosities appeared to be GABAergic. The vast proportion of sleep-max Nb+/MCH− neurons (81%) discharged maximally during paradoxical sleep (PS, called “P-max”) in negative correlation with EMG amplitude and from Nb-labeled varicosities also appeared to be predominantly GABAergic. Given their discharge profiles across the sleep-wake cycle, P-max together with S-max GABAergic neurons could thus serve to inhibit other neurons of the arousal systems, including local Orx neurons in the LH. They could accordingly dampen arousal with muscle tone and promote sleep, including PS with muscle atonia.
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