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

Zhang Fengwei1; Mak Sarah O.K.1; Liu Yuchu1; Ya Ke2,3; Rao Feng4; Yung Wing Ho2,3; Zhang Li5,6; Chow Billy Kwok Chong1

2022-11-21

10.1016/j.cub.2022.09.037

CURRENT BIOLOGY   Impact Factor & Quartile

0960-9822

1879-0445

In mammals, thirst is strongly influenced by the subfornical organ (SFO), a forebrain structure that integrates circulating signals including osmotic pressure and sodium contents. Secretin (SCT), a classical gastrointestinal hormone, has been implicated as a humoral factor regulating body-fluid homeostasis. However, the neural mechanism of secretin in the central nervous system in managing thirst remains unclear. In this study, we report that the local ablation of SCT receptor (SCTR) in the SFO reduces water but not salt intake in dehydrated mice and this effect could not be rescued by exogenous SCT administration. Electrophysiology with single-cell RT-PCR indicates that SCT elicits inward currents in the SFO neuronal nitric oxide synthase (SFOnNOS) neurons via SCTR in the presence of glutamate receptor antagonists. We further show that the SCTR in the SFO permits the activation of SFOnNOS neurons under distinct thirst types. Projection-specific gene deletion of SCTR in SFO to the median preoptic nucleus (MnPO) pathway also reduces water intake in dehydrated animals. SCT signaling thus plays an indispensable role in driving thirst. These data not only expand the functional boundaries of SCTR but also provide insights into the central mechanisms of homeostatic regulation.

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Shenzhen Municipal Government["JCYJ20170412153517422","KQJSCX20180322152418316"] ; National Natural Science Foundation of China[32070955] ; Hong Kong Government["GRF 17127718","GRF 17113120","GRF 17126222"]

Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology

Biochemistry & Molecular Biology ; Biology ; Cell Biology

WOS:000946528100005

CELL PRESS

BIOLOGY & BIOCHEMISTRY

Web of Science

1.School of Biological Sciences, The University of Hong Kong
2.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong
3.Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong
4.School of Life Sciences, Department of Biology, Southern University of Science and Technology
5.Key Laboratory of CNS Regeneration (Ministry of Education), GHM Institute of CNS Regeneration, Jinan University
6.Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences

Zhang Fengwei,Mak Sarah O.K.,Liu Yuchu,et al. Secretin receptor deletion in the subfornical organ attenuates the activation of excitatory neurons under dehydration[J]. CURRENT BIOLOGY,2022,32(22).

Zhang Fengwei.,Mak Sarah O.K..,Liu Yuchu.,Ya Ke.,Rao Feng.,...&Chow Billy Kwok Chong.(2022).Secretin receptor deletion in the subfornical organ attenuates the activation of excitatory neurons under dehydration.CURRENT BIOLOGY,32(22).

Zhang Fengwei,et al."Secretin receptor deletion in the subfornical organ attenuates the activation of excitatory neurons under dehydration".CURRENT BIOLOGY 32.22(2022).