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.