High salt recruits aversive taste pathways

High concentrations of salt activate sour- and bitter-taste-sensing cells in the tongues of mice, and genetic silencing of these pathways abolishes behavioural aversion to concentrated salt; this ‘co-opting’ of the two primary aversive taste pathways (sour and bitter) may have evolved so that high salt levels reliably trigger behavioural rejection. In contrast to the other four basic tastes (sweet, umami, sour and bitter), which are either appetitive or aversive, sodium salt can be both attractive and repulsive, depending on concentration. Lower concentrations of salt are perceived by cells expressing the sodium channel ENaC. In this study, Charles Zuker and colleagues show that high levels of salt activate the sour and bitter taste-sensing cells, and that salt-avoidance behaviours are abolished in mice lacking these pathways. The authors conclude that 'co-opting' the two primary aversive taste pathways causes the animals to reject foodstuffs containing extreme — and potentially harmful — levels of salt. Given current concerns about excessive dietary salt intake in humans, this work raises the prospect of developing selective receptor-cell modulators to help to control or even satisfy our strong appetite for salt without the potential ill effects of too much sodium. In the tongue, distinct classes of taste receptor cells detect the five basic tastes; sweet, sour, bitter, sodium salt and umami1,2. Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive and generally attractive to animals. By contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one3,4,5,6,7. This appetitive–aversive balance helps to maintain appropriate salt consumption3,4,6,8, and represents an important part of fluid and electrolyte homeostasis. We have shown previously that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaC8, but the cellular substrate for salt aversion was unknown. Here we examine the cellular and molecular basis for the rejection of high concentrations of salts. We show that high salt recruits the two primary aversive taste pathways by activating the sour- and bitter-taste-sensing cells. We also demonstrate that genetic silencing of these pathways abolishes behavioural aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways show unimpeded, continuous attraction even to very high concentrations of NaCl. We propose that the ‘co-opting’ of sour and bitter neural pathways evolved as a means to ensure that high levels of salt reliably trigger robust behavioural rejection, thus preventing its potentially detrimental effects on health.