Article

Separate circuitries encode the hedonic and nutritional values of sugar

  • Nature Neuroscience volume 19, pages 465470 (2016)
  • doi:10.1038/nn.4224
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Abstract

Sugar exerts its potent reinforcing effects via both gustatory and post-ingestive pathways. It is, however, unknown whether sweetness and nutritional signals engage segregated brain networks to motivate ingestion. We found in mice that separate basal ganglia circuitries mediated the hedonic and nutritional actions of sugar. During sugar intake, suppressing hedonic value inhibited dopamine release in ventral, but not dorsal, striatum, whereas suppressing nutritional value inhibited dopamine release in dorsal, but not ventral, striatum. Consistently, cell-specific ablation of dopamine-excitable cells in dorsal, but not ventral, striatum inhibited sugar's ability to drive the ingestion of unpalatable solutions. Conversely, optogenetic stimulation of dopamine-excitable cells in dorsal, but not ventral, striatum substituted for sugar in its ability to drive the ingestion of unpalatable solutions. Our data indicate that sugar recruits a distributed dopamine-excitable striatal circuitry that acts to prioritize energy-seeking over taste quality.

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Acknowledgements

This work was supported by US National Institutes of Health grants R01DC014859 and R01CA180030 (to I.E.d.A.), and R01 DK103176, DK084052 and NS48476 (to A.N.v.d.P.), the China Scholarship Council 201206260072 (to W.H.) and FAPESP (Sao Paulo) 2013/09405-3 (to T.L.F.).

Author information

Affiliations

  1. The John B. Pierce Laboratory, New Haven, Connecticut, USA.

    • Luis A Tellez
    • , Wenfei Han
    • , Tatiana L Ferreira
    • , Isaac O Perez
    •  & Ivan E de Araujo
  2. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Luis A Tellez
    • , Wenfei Han
    • , Tatiana L Ferreira
    •  & Ivan E de Araujo
  3. Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Xiaobing Zhang
    •  & Anthony N van den Pol
  4. Mathematics, Computing and Cognition Center, Federal University of ABC, Santo André SP, Brazil.

    • Tatiana L Ferreira
  5. Department of Physiology and Biophysics, Biomedical Sciences Institute, University of São Paulo, São Paulo SP, Brazil.

    • Sara J Shammah-Lagnado
  6. Department of Physiology, Yale University School of Arts and Sciences, New Haven, Connecticut, USA.

    • Ivan E de Araujo

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Contributions

I.E.d.A. conceived the study. I.E.d.A. and L.A.T. designed the experiments. L.A.T., W.H. and T.L.F. performed gastrointestinal and stereotaxic surgeries, performed behavioral and optogenetic experiments, performed microdialysis studies and analyzed data. W.H., S.J.S.-L. and T.L.F. performed histological analysis and imaging. X.Z. and A.N.v.d.P. performed whole-cell patch-clamp experiments, performed high-res imaging of brain slices and analyzed data. I.O.P. and L.A.T. performed in vivo electrophysiological experiments and analyzed data. I.E.d.A. wrote the manuscript. All of the authors actively participated in interpreting all data and in manuscript editing.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ivan E de Araujo.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–12

  2. 2.

    Supplementary Methods Checklist

Videos

  1. 1.

    Optically-driven intake of an unpalatable bitter solution.

    A mouse expressing the blue light-sensitive depolarizing channel ChR2 in dopamine-excitable D1r-expressing cells of dorsal striatum is shown. Upon contacting the bitter taste-containing sipper with the tongue, a blue laser pulse is delivered to the animal's dorsal striatum via the bilaterally implanted optical fibers. When laser source is OFF, the animal quickly interrupts licking, retracts to the opposite corner of the cage, and displays negative taste reactions. In contrast, incessant licking is observed when laser source is ON.