Secretin receptor deletion in the subfornical organ attenuates the activation of excitatory neurons under dehydration

TMEM63B functions as a mammalian thirst receptor

“…For the two-choice consumption preference assay, mice in the osmotic thirst model or dehydrated thirst model were tested for the choice of water or 0.3 M NaCl (Figure 6A). Consistent with previous studies 1,11,17,41 , acute osmotic stress with hypertonic solution induced selective consumption of water over the 0.3 M NaCl solution (Figure S11A). Moreover, the number of licks and the drinking volume of water of Tmem63b knockout mice were greatly reduced compared with those of wild-type mice (Figure 6B).…”

“…SFO excitatory neuron activation is necessary and sufficient for the generation of thirst 11,13,14,18,21,22,27,41–43 , but it is still unclear whether SFO excitatory neurons work as the primary sensory neurons to transduce osmolarity changes into neuronal signals and the sensory receptors in these neurons that mediate thirst also remain unknown 4 . To examine whether SFO excitatory neurons can be directly activated by hypertonic stimuli, physiological recordings of these neurons under hypertonic stimulation were carried out.…”

“…Having found that TMEM63B is required for the activation of SFO excitatory neurons during thirst stress and that TMEM63B is a pore-forming subunit to detect osmolarity changes, to finally determine whether TMEM63B is the mammalian thirst receptor, we investigated if TMEM63B plays a role in mediating thirst behavior in mice. We examined the drinking behavior of Tmem63b knockout mice in the osmotic thirst model and dehydrated thirst model, employing a two-choice consumption preference assay 1,11,17,41 . For the osmotic thirst model, mice were injected with 2 M NaCl intraperitoneally.…”

“…SFO excitatory neuron activation is necessary and sufficient for the generation of thirst 11,13,14,18,21,22,27,[41][42][43] , but it is still unclear whether SFO excitatory neurons work as the primary sensory neurons to transduce osmolarity changes into neuronal signals and the sensory receptors in these neurons that mediate thirst also remain unknown 4 .…”

“…Excitatory neurons in the SFO are necessary and sufficient for the induction of thirst 11,13,14,18,21,22,27,[41][42][43] , but it is still unclear whether SFO excitatory neurons are the interoceptive neurons that sense blood osmolarity changes directly. We first demonstrated that SFO excitatory neurons can be directly activated by hypertonic stimuli.…”