Curr Biol. 2022 Nov 21;32(22):4832-4841.e5. doi: 10.1016/j.cub.2022.09.037. Epub 2022 Oct 10.
Secretin receptor deletion in the subfornical organ attenuates the activation of excitatory neurons under dehydration
School of Biological Sciences, The University of Hong Kong, Hong Kong, China. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Hong Kong, China. School of Life Sciences, Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, China. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Hong Kong, China. Key Laboratory of CNS Regeneration (Ministry of Education), GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao, China. Electronic address: email@example.com. School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Service type: Knockout mice
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.
Keywords: dehydration; neuronal nitric oxide synthase; secretin; subfornical organ; thirst.