High salt recruits aversive taste pathways

In the tongue, distinct classes of taste receptor cells detect the five basic tastes, sweet, sour, bitter, sodium salt, and umami(1,2). Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive, and generally attractive to animals. In contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one(3–7). This appetitive-aversive balance helps maintain appropriate salt consumption(3,4,6,8), and represents an important part of fluid and electrolyte homeostasis. We have previously shown that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaC(8), while the cellular substrate for salt aversion was unknown. Here we explore the cellular and molecular basis for the rejection of high concentrations of salts (>300 mM NaCl or KCl). We now 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 behavioral aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways now exhibit unimpeded, continuous attraction even to exceedingly 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 behavioral rejection, thus preventing its potentially detrimental effects in health and well-being.