Supporting data for “Secretin Drives Thirst by Activating Glutamatergic Neurons in the Subfornical Organ”

Secretin (SCT) is a neuropeptide in the brain that regulates body fluid balance, while the neural basis of SCT that drive thirst remain unclear. Here, we demonstrate that the SCT-SCT receptor (SCTR) axis in the subfornical organ (SFO) is involved in water intake but not salt appetite. SFO-specific Sctr deletion reduces the activity of SFO glutamatergic (SFOnNOS) neurons under water-depleted conditions. We then show that SCTR in the SFO is partially responsible for mediating the dipsogenic action of angiotensin II (Ang II). Furthermore, electrophysiology with single-cell reverse transcription PCR indicates that SCT directly activates SFOnNOS neurons via SCTR in a cell-autonomous manner. Additionally, local Sctr deletion in the median preoptic nucleus (MnPO), the major downstream nucleus of SFO, reduces water intake in dehydrated animals. A projection-specific gene deletion approach also shows that SCT and SCTR in SFO→MnPO neurons are necessary for water intake under dehydration. The present study thus reveals SCT/SCTR-dependent neural mechanisms in the central nervous system to drive thirst.促胰液素（Secretin, SCT）是脑中的一类神经肽，参与机体体液平衡的调控，但其驱动口渴反应的神经基础仍未明确。本研究证实，穹窿下器（subfornical organ, SFO）内的SCT-SCT受体（SCTR）信号轴参与饮水行为调控，但不影响摄盐偏好。在缺水状态下，SFO特异性敲除Sctr会降低穹窿下器谷氨酸能神经元（SFOnNOS）的活动。进一步研究表明，SFO中的SCTR可部分介导血管紧张素II（angiotensin II, Ang II）的促饮水作用。此外，结合单细胞逆转录PCR的电生理学实验显示，SCT可通过SCTR以细胞自主方式直接激活SFOnNOS神经元。正中视前核（median preoptic nucleus, MnPO）作为SFO的主要下游核团，其局部Sctr敲除会减少脱水动物的饮水量。采用投射特异性基因敲除策略的实验也证实，SFO→MnPO神经元中的SCT与SCTR是脱水状态下饮水行为所必需的。综上，本研究揭示了中枢神经系统内依赖SCT/SCTR的神经机制，该机制可驱动口渴反应。