Faculty, Staff and Student Publications

Language

English

Publication Date

12-21-2023

Journal

Cell

DOI

10.1016/j.cell.2023.10.020

PMID

37989313

PMCID

PMC10761003

PubMedCentral® Posted Date

12-21-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Animals, Neural Pathways, Sodium, Taste, Mice, Gene Expression Profiling, Receptors, Prostaglandin E, EP3 Subtype

Published Open-Access

yes

nihms-1943313-f0008.jpg (173 kB)
Graphical Abstract

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