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.

中文翻译：

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口渴调节的分层神经结构

食欲的神经回路受到稳态扰动和摄入行为的调节。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，我们在小鼠身上展示了终板中的兴奋性神经群形成了分层电路结构来调节口渴。其中，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至关重要。相反，涉及表达胰高血糖素样肽 1 受体 (GLP1R) 的 MnPO GABA 能神经元的独特抑制回路在饮酒后立即激活，并单突触抑制 SFO 口渴神经元。这些反应是由摄入液体而不是固体引起的，并且与饮酒的开始和结束时间相关。此外，对表达 GLP1R 的 MnPO 神经元进行功能丧失操作会导致烦渴、过度饮酒的表型。因此，这些神经元通过监测实时液体摄入来促进口渴的快速饱足。我们的研究揭示了动态口渴回路，该回路整合了对液体的稳态本能需求和随后的饮水行为，以维持内部水分平衡。