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Published December 21, 2023 | Published
Journal Article Open

Parallel neural pathways control sodium consumption and taste valence


The hedonic value of salt fundamentally changes depending on the internal state. High concentrations of salt induce innate aversion under sated states, whereas such aversive stimuli transform into appetitive ones under sodium depletion. Neural mechanisms underlying this state-dependent salt valence switch are poorly understood. Using transcriptomics state-to-cell-type mapping and neural manipulations, we show that positive and negative valences of salt are controlled by anatomically distinct neural circuits in the mammalian brain. The hindbrain interoceptive circuit regulates sodium-specific appetitive drive , whereas behavioral tolerance of aversive salts is encoded by a dedicated class of neurons in the forebrain lamina terminalis (LT) expressing prostaglandin E2 (PGE2) receptor, Ptger3. We show that these LT neurons regulate salt tolerance by selectively modulating aversive taste sensitivity, partly through a PGE2-Ptger3 axis. These results reveal the bimodal regulation of appetitive and tolerance signals toward salt, which together dictate the amount of sodium consumption under different internal states.

Copyright and License

© 2023 Elsevier.


We thank the members of the Oka laboratory and Sangjun Lee for their helpful discussion and feedback comments. We thank Ashil Koranne and Jacob Hauser for maintaining and genotyping animal lines and the Single-Cell Profiling and Engineering Center (SPEC) in the Beckman Institute at Caltech. R.P. thanks Serina Tsang and Kathy Kafer for help generating the Ptger3^(Cre) mice and Susan Phelps for mouse husbandry. We thank Henry Lester and Anand K. Muthusamy for their support for the photometry recording setup and Tomomi Karigo for caspase virus. This work was supported by Startup funds from the President and Provost of the California Institute of Technology and the Biology and Biological Engineering Division of the California Institute of Technology. Y.O. is supported by the New York Stem Cell Foundation, the NIH (R01NS109997 and R01NS123918), the Alfred P. Sloan Foundation, the Edward Mallinckrodt Foundation, and the Heritage Medical Research Institute. Y.Z. was supported by the Chen Graduate Fellowship.


Y.Z. and Y.O. conceived the research program and designed experiments. Y.Z. performed genetic and behavioral experiments and analyzed the data. E.K. supported behavioral and histological analysis. R.P. generated and maintained Ptger3^(Cre) transgenic mice. Y.Z., T.W., and A.H.P. performed single-cell RNA sequencing experiments and analyzed the data. T.W., B.Z., L.D., and K.F. performed seqFISH experiments. Y.Z. and L.L. performed and analyzed fiber photometry experiments. Y.Z. and Y.O. wrote the paper. Y.O. supervised the entire work.

Additional Information

We support inclusive, diverse, and equitable conduct of research. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list.

Conflict of Interest

The authors declare no competing interests.


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Additional details

November 21, 2023
January 9, 2024