Decoding how the brain manages the appetite for salt and water

Staying hydrated and consuming appropriate amounts of salt is essential for the survival of land animals, including humans. The human brain has several regions constituting neural circuits that regulate thirst and appetite for salt, in intriguing ways.

Previous studies have suggested that ingestion of water or salt rapidly suppresses thirst and appetite for salt before the digestive system absorbs the ingested substances, indicating the presence of sensing and feedback mechanisms in the digestive organs that help modulate thirst and appetite for salt in real time in response to drinking and eating. . Unfortunately, despite extensive research on this topic, the details of these underlying mechanisms have remained elusive.

To shed light on this subject, a Japanese research team conducted an in-depth study on the parabrachial nucleus (PBN), the brain’s relay center for ingestion signals from the digestive organs. Their latest paper, first authored by Assistant Professor Takashi Matsuda of the Tokyo Institute of Technology, was published in Cell Reports.

The researchers conducted a series of in vivo experiments using genetically modified mice. They introduced optogenetic (and chemogenetic) modifications and in vivo calcium imaging techniques into these mice, allowing them to visualize and control the activation or inhibition of specific neurons in the lateral PBN (LPBN) at the help of light (and chemicals).

During the experiments, the researchers offered the mice – either under normal conditions or under water- or salt-depleted conditions – water and/or salt water, and monitored neuronal activities as well as corresponding alcohol consumption behaviors.

In this way, the team identified two distinct subpopulations of cholecystokinin mRNA-positive neurons in the LPBN, which underwent activation upon water and salt consumption. The neuronal population that responds to water intake projects runs from the LPBN to the medial preoptic nucleus (MnPO), while that that responds to salt intake projects goes to the ventral bed nucleus of the stria terminalis (vBNST).

Interestingly, if the researchers artificially activated these neuronal populations through optogenetic experiments (genetic control using light), the mice drank significantly less water and ingested less salt, even though they were previously deprived water or salt. Similarly, when the researchers chemically inhibited these neurons, the mice consumed more water and salt than usual.

Therefore, these LPBN neuronal populations are involved in feedback mechanisms that reduce thirst and appetite for salt upon water or salt ingestion, possibly helping to prevent excessive water or salt consumption. salt. These results, alongside their previous neurological studies, also reveal that MnPO and vBNST are the control centers for thirst and salty appetite, integrating promotion and suppression signals from several other brain regions.

“Understanding the brain mechanisms controlling water and salt consumption behaviors is not only an important discovery in the fields of neuroscience and physiology, but also provides valuable information for understanding the mechanisms underlying induced diseases by excessive consumption of water and salt, such as water intoxication, polydipsia, and salt-sensitive hypertension,” notes Dr. Matsuda.

Professor Noda mentions: “Many neural mechanisms governing fluid homeostasis remain unknown. We still need to understand how signals to induce and suppress water and salt intake, accumulated in the MnPO and vBNST, are integrated and function to control drinking behaviors.