Extended Data Fig. 8: Glutamatergic MnPO neurons relay the gastrointestinal osmosensory signal to vasopressin neurons.
From: A gut-to-brain signal of fluid osmolarity controls thirst satiation
a–d, Glutamatergic MnPO neurons are necessary for relaying gastrointestinal osmosensory information to SON vasopressin neurons. a, Schematic for simultaneous fibre photometry recording of vasopressin neurons and chemogenetic inhibition of glutamatergic MnPO neurons. Scale bar, 100 μm. b, Injection of CNO inhibited water intake after dehydration (n = 5 mice). c, Example of vasopressin neuron dynamics during intraperitoneal injection of CNO or vehicle (left) and subsequent intragastric infusion of 1.5 M NaCl by oral gavage (right). Inset, water intake after dehydration for the example mouse. d, Quantification of vasopressin neuron response to intraperitoneal injection (left) and NaCl intragastric infusion (right) (n = 5 mice, two-tailed Student’s t-tests). e–h, Glutamatergic MnPO neurons are not necessary for relaying gastrointestinal osmosensory information to SFO thirst neurons. e, Schematic for simultaneous fibre photometry recording of SFO neurons and chemogenetic inhibition of glutamatergic MnPO neurons. Scale bar, 100 μm. f, Injection of CNO inhibited water intake after dehydration (n = 5 mice). g, Example of SFO neuron dynamics during intragastric infusion of 1.5 M NaCl by oral gavage, after intraperitoneal injection CNO or vehicle. Inset, water intake after dehydration for the example mouse. h, Quantification of SFO neuron response to intraperitoneal injection (left) and intragastric infusion of NaCl (right) (n = 5 mice, two-tailed Student’s t-tests). i, CNO inhibits drinking in mice that express the Gi-coupled human M4D designer receptor (hM4D(Gi)) in glutamatergic MnPO neurons but not in control mice that lack hM4D(Gi). i, Injection of CNO significantly inhibited water intake after dehydration in MnPOCamk2a::hM4D(Gi) + SON mice with photometry implants (n = 5 mice; quantified from b) and MnPONos1::hM4D(Gi) + SFO mice with photometry implants (n = 5 mice; quantified from f) but not in control mice (n = 6 mice, two-way ANOVA, Holm–Šídák correction). Error bars and shaded areas represent mean ± s.e.m. n.s., not significant; *P < 0.05, **P < 0.01. The mouse brains in this figure have been reproduced with permission from ref. 35, Copyright © 2012.
