Hierarchical neural architecture underlying thirst regulation.
Hierarchical neural architecture underlying thirst regulation.
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DOI：
10.1038/nature25488
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发表时间：
2018-03-08
期刊：
影响因子：
64.8
通讯作者：
Oka Y
中科院分区：
文献类型：
--
作者：
Augustine V;Gokce SK;Lee S;Wang B;Davidson TJ;Reimann F;Gribble F;Deisseroth K;Lois C;Oka Y
食欲的神经回路受体内平衡扰动和摄食行为的调节。然而，整合这些内部和外部刺激的电路组织尚不清楚。在这里，我们表明，在小鼠的兴奋性神经群体的终板形成一个层次电路架构，以调节口渴。其中，在正中视前核（MnPO）中表达一氧化氮合酶的神经元对于整合来自穹窿下器官（SFO）的口渴驱动神经元的信号是必不可少的。相反，涉及表达胰高血糖素样肽1受体（GLP 1 R）的MnPO GABA能神经元的独特抑制回路在饮酒后立即被激活，并单突触抑制SFO口渴神经元。这些反应是由液体而不是固体的摄入引起的，并且与饮酒的开始和结束时间是时间锁定的。此外，GLP1R表达的MnPO神经元的功能丧失操作导致了多饮，过度饮酒表型。因此，这些神经元通过实时监测液体摄入来促进口渴的快速饱足感。我们的研究揭示了动态口渴回路，它整合了对液体的稳态本能需求和随之而来的饮水行为，以保持内部水平衡。
Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal and external stimuli is unclear. Here we show in mice that excitatory neural populations in the lamina terminalis form a hierarchical circuit architecture to regulate thirst. Among them, nitric oxide synthase-expressing neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Conversely, a distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of GLP1R-expressing MnPO neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. Our study reveals dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behaviour to maintain internal water balance.
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影响因子：
4.8
作者：
JOHNSON, AK;GROSS, PM
通讯作者：
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影响因子：
25
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影响因子：
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