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Chemosensory modulation of neural circuits for sodium appetite

Lee, Sangjun and Augustine, Vineet and Zhao, Yuan and Ebisu, Haruka and Ho, Brittany and Kong, Dong and Oka, Yuki (2019) Chemosensory modulation of neural circuits for sodium appetite. Nature, 568 (7750). pp. 93-97. ISSN 0028-0836. PMCID PMC7122814. doi:10.1038/s41586-019-1053-2.

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[img] Image (JPEG) (Extended Data Fig. 1: Behavioural paradigms for sodium-appetite induction and histological analysis of the pre-LC) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 2: Sodium appetite induced by the photostimulation of pre-LCPDYN neurons) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 3: Optogenetic and chemogenetic inhibition of pre-LCPDYN neurons) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 5: In vivo activity of pre-LCPDYN neurons after ingestive behaviours) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 6: Functional analysis of the NTSHSD2→pre-LCPDYN connections) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 7: Histological analysis of putative upstream brain structures of pre-LCPDYN neurons) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 8: Downstream projections of pre-LCPDYN neurons) - Supplemental Material
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Sodium is the main cation in the extracellular fluid and it regulates various physiological functions. Depletion of sodium in the body increases the hedonic value of sodium taste, which drives animals towards sodium consumption. By contrast, oral sodium detection rapidly quenches sodium appetite, suggesting that taste signals have a central role in sodium appetite and its satiation. Nevertheless, the neural mechanisms of chemosensory-based appetite regulation remain poorly understood. Here we identify genetically defined neural circuits in mice that control sodium intake by integrating chemosensory and internal depletion signals. We show that a subset of excitatory neurons in the pre-locus coeruleus express prodynorphin, and that these neurons are a critical neural substrate for sodium-intake behaviour. Acute stimulation of this population triggered robust ingestion of sodium even from rock salt, while evoking aversive signals. Inhibition of the same neurons reduced sodium consumption selectively. We further demonstrate that the oral detection of sodium rapidly suppresses these sodium-appetite neurons. Simultaneous in vivo optical recording and gastric infusion revealed that sodium taste—but not sodium ingestion per se—is required for the acute modulation of neurons in the pre-locus coeruleus that express prodynorphin, and for satiation of sodium appetite. Moreover, retrograde-virus tracing showed that sensory modulation is in part mediated by specific GABA (γ-aminobutyric acid)-producing neurons in the bed nucleus of the stria terminalis. This inhibitory neural population is activated by sodium ingestion, and sends rapid inhibitory signals to sodium-appetite neurons. Together, this study reveals a neural architecture that integrates chemosensory signals and the internal need to maintain sodium balance.

Item Type:Article
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URLURL TypeDescription ReadCube access CentralArticle
Lee, Sangjun0000-0002-0846-8252
Augustine, Vineet0000-0003-4431-1663
Oka, Yuki0000-0003-2686-0677
Additional Information:© 2019 Springer Nature Publishing AG. Received 18 September 2018; Accepted 31 January 2019; Published 27 March 2019. Data availability: Data and code are available from the corresponding author upon reasonable request. We thank the members of the Oka laboratory and D. J. Anderson for discussion and comments; B. Lowell and M. Krashes for providing PDYN–Cre mice; A. Fejes-Toth for HSD2–Cre mice; and Y. Peng for real-time mouse tracking software. This work was supported by Startup funds from California Institute of Technology. Y.O. is supported by the Searle Scholars Program, the Mallinckrodt Foundation, the McKnight Foundation, the Klingenstein-Simons Foundation, and the National Institutes of Health (NIH) (R56MH113030, R01NS109997). D.K. is supported by the NIH (R01 DK108797 and R01 NS107315). H.E. is supported by the Japan Society for the Promotion of Science. Reviewer information: Nature thanks Charles Bourque, Ivan de Araujo and Michael McKinley for their contribution to the peer review of this work. Author Contributions: S.L. and Y.O. conceived the research programme and designed the experiments. S.L. performed the experiments and analysed the data, with help from V.A. and Y.O. H.E. and B.H. performed intragastric surgery. Y.Z. performed all slice patch-clamp recordings. D.K. generated and maintained the PDYN–GFP animals. S.L. and Y.O. wrote the paper. Y.O. supervised the work. The authors declare no competing interests.
Group:Tianqiao and Chrissy Chen Institute for Neuroscience
Funding AgencyGrant Number
Searle Scholars ProgramUNSPECIFIED
Mallinckrodt FoundationUNSPECIFIED
McKnight FoundationUNSPECIFIED
Klingenstein-Simons FoundationUNSPECIFIED
NIHR01 DK108797
NIHR01 NS107315
Japan Society for the Promotion of Science (JSPS)UNSPECIFIED
Subject Keywords:Feeding behaviour; Neural circuits; Neuronal physiology
Issue or Number:7750
PubMed Central ID:PMC7122814
Record Number:CaltechAUTHORS:20190122-131625102
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92400
Deposited By: George Porter
Deposited On:27 Mar 2019 20:41
Last Modified:16 Nov 2021 03:50

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