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.

分泌素（SCT）是一种存在于大脑中的神经肽，它调节体液平衡，而驱动口渴的SCT的神经基础尚不明确。本研究揭示了SFO（亚室周器官）中的SCT-SCT受体（SCTR）轴参与水分摄入，但不参与盐分食欲。在SFO特异性Sctr敲除的条件下，SFO的谷氨酸能（SFOnNOS）神经元活性降低。我们进一步表明，SFO中的SCTR部分介导了血管紧张素II（Ang II）的利尿作用。此外，通过单细胞逆转录PCR的电生理学研究表明，SCT通过SCTR以细胞自主的方式直接激活SFOnNOS神经元。此外，在中线前丘脑核（MnPO），SFO的主要下游核团，局部Sctr敲除减少了脱水动物的水分摄入。采用特定投射基因敲除方法也显示，在脱水条件下，SFO至MnPO神经元中的SCT和SCTR对于水分摄入是必需的。因此，本研究揭示了中枢神经系统中SCT/SCTR依赖的神经机制，该机制驱动口渴。