A significant advancement has been made in understanding how the brain regulates thirst and salt cravings.
Maintaining optimal hydration and electrolyte balance, particularly sodium from salt, is crucial for the well-being of land-dwelling creatures, including ourselves. Intriguingly, the human brain possesses specific areas that regulate thirst and salt cravings through complex neural pathways.
Previous studies were suggested that water or salt being ingested quickly is suppressed thirst and salt appetite before the digestive system is absorbed the ingested substances, being indicated the existence of sensing and feedback mechanisms are present in digestive organs that contribute to real-time thirst and salt appetite regulation in response to drinking and feeding. Unfortunately, despite extensive having been conducted on this subject, the details of these underlying mechanisms remain elusive.
The Study
In a quest to understand the underlying mechanisms of thirst and salt appetite modulation, a research team in Japan recently conducted a detailed investigation on the parabrachial nucleus (PBN), the brain region responsible for relaying ingestion signals from the digestive organs.
To achieve this, researchers employed a series of in vivo experiments utilizing genetically modified mice. These mice were introduced with optogenetic (and chemogenetic) modifications alongside in vivo calcium imaging techniques. This allowed for visualization and control of specific neuron activation or inhibition within the lateral PBN (LPBN) through the use of light (and chemicals).
The experiments involved offering water and/or salt water to the mice under various conditions, including regular, water-depleted, and salt-depleted states. This facilitated the monitoring of neural activity alongside corresponding drinking behaviors.
Through this investigation, two distinct groups of neurons expressing cholecystokinin mRNA within the LPBN were identified. These neurons became activated upon water and salt intake. The group responding to water intake projects from the LPBN to the median preoptic nucleus (MnPO), while the one responding to salt intake projects to the ventral bed nucleus of the stria terminalis (vBNST).
Interestingly, by artificially activating these neuronal populations via optogenetic techniques (light-based genetic control), researchers observed a significant decrease in water and salt consumption by the mice, even in previously water- or salt-deprived conditions. Conversely, chemical inhibition of these neurons resulted in increased water and salt intake compared to normal levels.
These findings suggest that the identified neuronal populations within the LPBN play a role in feedback mechanisms that suppress thirst and salt appetite following water or salt ingestion, potentially aiding in preventing overconsumption of water or salt.
Building upon previous neurological research, these findings further illuminate the role of MnPO and vBNST as key regulators of thirst and salt appetite. These brain regions integrate stimulatory and inhibitory signals originating from various areas within the brain.
Assistant Professor Takashi Matsuda from Tokyo Institute of Technology
“Understanding the brain mechanisms that control water and salt intake behaviors represents a major advancement not only in neuroscience and physiology, but also provides valuable insights into the mechanisms behind diseases caused by excessive water or salt intake, such as water intoxication, polydipsia, and salt-sensitive hypertension.”
Masaharu Noda
“Many neural mechanisms governing fluid balance remain to be discovered. We require further investigation to understand how the signals for promoting and suppressing water and salt intake, converging within the MnPO and vBNST, are integrated and influence our intake behaviors.”
https://doi.org/10.1016/j.celrep.2023.113619
Summary
Thirst and salt appetite are temporarily suppressed after water and salt ingestion, respectively, before absorption; however, the underlying neural mechanisms remain unclear. The parabrachial nucleus (PBN) is the relay center of ingestion signals from the digestive organs. We herein identify two distinct neuronal populations expressing cholecystokinin (Cck) mRNA in the lateral PBN that are activated in response to water and salt intake, respectively. The two Cck neurons in the dorsal-lateral compartment of the PBN project to the median preoptic nucleus and ventral part of the bed nucleus of the stria terminalis, respectively. The optogenetic stimulation of respective Cck neurons suppresses thirst or salt appetite under water- or salt-depleted conditions. The combination of optogenetics and in vivo Ca2+ imaging during ingestion reveals that both Cck neurons control GABAergic neurons in their target nuclei. These findings provide the feedback mechanisms for the suppression of thirst and salt appetite after ingestion.