The cellular basis of distinct thirst modalities.

The cellular basis of distinct thirst modalities.
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DOI:
10.1038/s41586-020-2821-8
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发表时间:
2020-12
期刊:
影响因子:
64.8
通讯作者:
Oka Y
Oka Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pool AH;Wang T;Stafford DA;Chance RK;Lee S;Ngai J;Oka Y

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摄入液体是一种基本的先天行为,主要由两种不同类型的口渴引起。血液渗透压升高会引起渗透性口渴,从而驱使动物饮用纯净水。相反,失去体液会引起低血容量性口渴,动物会同时寻求水和矿物质(盐)来恢复血量。终板(LT)中的室周器官(CVO)是感觉两种类型的口渴刺激的关键部位。然而,不同的口渴模式在大脑中是如何编码的仍不清楚。在这里,我们使用刺激到细胞类型映射使用单细胞RNA-seq(scRNA-seq)来确定不同类型口渴的细胞底物。这些研究揭示了每个CVO结构中不同的兴奋性和抑制性神经元类型。其中,我们展示了在渗透和低血容量应激下,神经元类型的独特组合被激活。这些结果阐明了不同口渴模式背后的细胞逻辑。此外,口渴模式特定细胞类型中的光遗传功能增益概括了由两种不同的致糖尿病刺激引起的特定于水和非特定液体的胃口。综上所述,这项研究表明,口渴是一种多模式的生理状态,不同的口渴状态是由哺乳动物大脑中特定的神经元类型介导的。
Fluid intake is an essential innate behavior mainly caused by two distinct types of thirst. Increased blood osmolality induces osmotic thirst that drives animals to consume pure water. Conversely, the loss of body fluid induces hypovolemic thirst in which animals seek both water and minerals (salts) to recover blood volume. Circumventricular organs (CVOs) in the lamina terminalis (LT) are critical sites for sensing both types of thirst-inducing stimuli. However, how different thirst modalities are encoded in the brain remains unknown. Here, we employed stimulus to cell-type mapping using single-cell RNA-seq (scRNA-seq) to determine the cellular substrate underlying distinct types of thirst. These studies revealed diverse excitatory and inhibitory neuron types in each CVO structure. Among them, we show that unique combinations of neuron types are activated under osmotic and hypovolemic stresses. These results elucidate the cellular logic underlying distinct thirst modalities. Furthermore, optogenetic gain-of-function in thirst-modality-specific cell types recapitulated water-specific and non-specific fluid appetite caused by the two distinct dipsogenic stimuli. Taken together, this study demonstrates that thirst is a multimodal physiological state, and that different thirst states are mediated by specific neuron types in the mammalian brain.
DOI: 10.1038/nature25488
发表时间: 2018-03-08
期刊: Nature
影响因子: 64.8
作者:
Augustine V;Gokce SK;Lee S;Wang B;Davidson TJ;Reimann F;Gribble F;Deisseroth K;Lois C;Oka Y
通讯作者: Oka Y
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发表时间: 2003-11-11
影响因子: 11.1
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通讯作者: Friedman, JM
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发表时间: 1993-05-01
期刊: FASEB JOURNAL
影响因子: 4.8
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影响因子: 64.8
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