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 (SFO^nNOS) 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 SFO^nNOS 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.