That sodium has a crucial role in body-fluid control has been known for many years, but how the brain controls behaviours that regulate water and sodium intake, and sodium's involvement in this process, are not fully understood. Now, research published in The Journal of Neuroscience has shed new light on salt-intake behaviour in mice.

The Nax channel is already known to be involved in salt intake, and Hiyama et al. compared the salt-intake behaviour of Nax-knockout and wild-type mice in a series of experiments. In each, all mice were provided with both distilled water and a 0.3 M NaCl solution to drink, and, while fully satiated with water, showed no marked preference for either. After 48 hours dehydration, wild-type mice were more sensitive to saline, and showed a strong preference for the distilled water. However, mutant mice did not show this increased sensitivity and continued to ingest similar amounts of saline solution and distilled water. As there is already evidence that Nax is not involved in tasting, the researchers proposed that the abnormal salt intake seen in dehydrated Nax-knockout mice is the result of brain defects.

Hiyama et al. then investigated the drinking behaviour of the mice during microinjection of different NaCl concentrations into the cerebral ventricle. Infusion of an isotonic solution (0.145 M NaCl) did not result in differences in behaviour between the wild-type and mutant mice, with both taking equivalent volumes of water and 0.3 M NaCl. However, when a hypertonic solution (0.5 M NaCl) was infused, wild-type mice showed a strong aversion to the saline solution, but mutant mice did not.

The expression of Nax is limited to a few regions of the CNS, including the subfornical organ (SFO), a circumventricular organ that is located in the forebrain. The authors showed that normal salt-intake behaviour could be rescued if the SFO was transfected with a Nax-expressing viral vector, indicating both that the SFO regulates salt-intake behaviour and that the Nax channel is the sensor that allows it to do so.