Study uncovers a neural circuit that prompts mice to stop drinking

Identifying the neural mechanisms that support the regulation of vital physiological processes, such as drinking, eating and sleeping, is a long-standing goal within the neuroscience research community. As the disruption of these processes can severely impact people’s health and everyday functioning, uncovering their neural and biological underpinnings is of the utmost importance.

New insights gathered by neuroscientists could ultimately inform the development of more effective interventions designed to regulate vital physiological processes. Thirst and hunger are known to be regulated by homeostatic processes, biological processes that allow the body to maintain internal stability.

Yet drinking behavior can also be anticipatory, which means that animals and humans often adjust their actions (i.e., stop drinking) before the concentration of substances in the blood changes in response to drinking water. The mechanisms through which the brain predicts when it is the right time to stop drinking remain poorly understood.

Researchers at Zhejiang Chinese Medical University and Zhejiang University recently carried out a study involving mice aimed at shedding new light on these mechanisms. Their findings, published in Nature Neuroscience, led to the identification of a neural pathway that reduces neural activity in specific regions of the mouse brain, signaling that the body has received enough water.

“Drinking behavior is not only homeostatically regulated but also rapidly adjusted before any changes in blood osmolality occur, known as anticipatory thirst satiation,” wrote Lingyu Xu, Yuhao Sun and their colleagues in their paper.

“Homeostatic and anticipatory signals converge in the subfornical organ (SFO); however, the neural pathways conveying peripheral information to the SFO before changes in blood composition are incompletely understood. We reveal an inhibitory pathway from the medial septum (MS) to the SFO that is involved in the control of anticipatory drinking behavior in mice.”

As part of their experiments, Xu, Sun and their colleagues observed the drinking behavior of adult mice, while recording their neural activity. This led to the discovery of a neural pathway connecting the MS, a small region in the mouse brain that contributes to the synchronization of brain circuits, and the SFO, a region implicated in the monitoring of bodily fluids.

“MS γ-aminobutyric acid (GABA)ergic neurons encode water-satiation signals by integrating cues from the oral cavity and tracking gastrointestinal signals,” wrote the authors. “These neurons receive inputs from the parabrachial nucleus and relay to SFO^CaMKII neurons, forming a bottom-up pathway with activity that prevents overhydration. Disruption of this circuit leads to excessive water intake and hyponatremia.”

Essentially, the researchers found that after a mouse starts drinking, GABAergic neurons in the MS become active and receive signals from the parabrachial nucleus, a brain region that processes signals originating from the mouth and gut. These GABAergic neurons then send inhibitory signals to neurons in the SFO, which in turn modulate the feeling of thirst.

Interestingly, when the team disrupted this pathway’s activity, they found that mice no longer stopped drinking and developed hyponatremia. This is a condition characterized by overhydration and an abnormally low concentration of sodium in the blood.

This recent study gathered new valuable insight into how the mouse brain prevents overhydration, signaling that it is time to stop drinking. Future studies could further examine the neural circuit identified by the researchers and probe the existence of a similar pathway in humans or other mammals. The discovery of a similar pathway in humans could help to better understand conditions associated with overhydration and dysregulated drinking behavior.

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