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High salt recruits aversive taste pathways

Oka, Yuki and Butnaru, Matthew and von Buchholtz, Lars and Ryba, Nicholas J. P. and Zuker, Charles S. (2013) High salt recruits aversive taste pathways. Nature, 494 (7438). pp. 472-475. ISSN 0028-0836. PMCID PMC3587117. doi:10.1038/nature11905.

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In the tongue, distinct classes of taste receptor cells detect the five basic tastes; sweet, sour, bitter, sodium salt and umami. 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 one. This appetitive–aversive balance helps to maintain appropriate salt consumption, 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, ENaC, 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.

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Additional Information:© 2013 Macmillan Publishers Limited. Received 20 August 2012; accepted 15 January 2013. Published online 13 February 2013. We thank E. Vitalis and N. Propp for the generation and maintenance of mouse lines, and K. Mueller for the construction of T2R-Sapphire lines. We also thank J. Chandrashekar, W. Sly and A. Waheed for advice and discussions, and K. Scott and members of our laboratories for comments. Y.O. was supported by the Japan Society for Promotion of Science. This research was supported in part by the intramural research program of the National Institutes of Health and National Institute of Dental and Craniofacial Research (to N.J.P.R.). C.S.Z. is an investigator of the Howard Hughes Medical Institute. Author Contributions: Y.O. designed the study, carried out electrophysiological, biochemical, pharmacological and behavioural experiments, analysed data and wrote the paper; M.B. carried out nerve recordings and behavioural studies; L.v.B. carried out nerve recordings and localization studies. N.J.P.R. and C.S.Z. designed the study, analysed data and wrote the paper. C.S.Z. is a scientific founder and scientific advisory board member of Senomyx.
Funding AgencyGrant Number
Japan Society for the Promotion of Science (JSPS)UNSPECIFIED
National Institute of Dental and Craniofacial Research (NIDCR)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:7438
PubMed Central ID:PMC3587117
Record Number:CaltechAUTHORS:20151118-134438051
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:62206
Deposited By: George Porter
Deposited On:18 Nov 2015 23:41
Last Modified:10 Nov 2021 22:59

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