Nature: How the brain tells what kind of thirst you are

the human body is a magical and complex system, even with the rapid development of science and technology today, our understanding of the mysteries of the human body is only the tip of the iceberg. The human body has important scientific research value, so it attracts generations of scientists to explore. Recently, scientists have uncovered the cellular basis of different forms of thirst, making us one step further in our exploration of the mysteries of the human body.On October 14th researchers from the Department of Biology and Bioengineering at the California Institute of Technology (CALF) discovered multiple transcriptional group cell types of thirsty neurons at the end of the final plate (flat nerve endings) and showed that unique combinations of neuron types can respond to and mediate different thirst states. The results are published in Nature.Liquid intake is a basic innate behavior, mainly caused by two different types of thirst. Thirst caused by elevated blood penetration pressure drives animals to ingest pure water, while thirst caused by fluid loss causes animals to seek both water and minerals (salt) to restore blood volume. CVO at the end of the end plate is a key part of detecting two types of thirst stimulation, but how to encode different forms of thirst in the brain remains unknown.Increased blood permeation pressure and/or loss of body fluids induce increased FOS expression in the dome substation (SFO) and the end-plate vascular region (OVLT) of the heterocephaly, which represents nerve activation. To find out if osmotic and blood flow pressure deficiencies were detected by the same neurons in CVO, the researchers used an activity-dependent genetic marker strategy to permanently label FOS-positive neurons. The results showed that injections of highly permeable saline caused strong markers in SFO and OVLT, compared with far fewer FOS markers caused by low blood volume. These results show that permeable thirst and low-volume thirst activate unique cell groups in CVO.The researchers then used single-cell RNA sequencing techniques to identify cell substrates that cause different types of thirst. The results showed that there were 12 and 13 major cell categories in SFO and OVLT, respectively. For further study, they found five types of excitability and three types of inhibitory neurons in SFO, and 6 types of excitability and 2 types of inhibitory neurons in OVLT.In addition, the researchers found that different thirst states activated a unique combination of cell types in CVO. At low blood volume, Glut1-Bmp3, an excitable neuron type in SFO and Glut1-Bmp3 in OVLT, is strongly activated, while other types of neurons are selectively activated by permeable pressure (SFO:Glut5-Rxfp3; OVLT:Glut4-Fam126a and Glut5-Rxfp1).Next, the researchers further identified the genetic markers most relevant to Foss activation patterns. The analysis found that the expression of human relaxin/insulin-like peptides 1 (Rxfp1) and Pdynogen were closely related to the neuroactivation patterns under high permeability and low capacity thirst, respectively. Subsequent gene-knocking experiments in mice confirmed this: after stimulating Rxfp1 neurons, the full animals showed a strong appetite for water but refused to consume high-permeable NaCl and other salts, while photogenetic stimulation of Pdyn neurons triggered non-specific drinking behavior for water and highly permeable salt solutions. In addition, chemical inhibition of Rxfp1-positive neurons can strongly inhibit osmotic pressure-induced water intake, while inhibition of Pdyn is not.In summary, the study sheds light on the cellular basis of the two thirsty ways and emphasizes the importance of dissecting nerve circuit function at the transcriptional group cell type level. In addition, functionally defined neuron groups typically contain subgroups that have related but distinct functions for implementing specific behaviors. (Biological Exploration):the cellular basis of the distinct thirst modalities