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Separate circuitries encode the hedonic and nutritional values of sugar

Nature Neuroscience volume 19, pages 465470 (2016) | Download Citation


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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  1. 1.

    Intragastric reinforcement effect. J. Comp. Physiol. Psychol. 69, 432–441 (1969).

  2. 2.

    Post-ingestive positive controls of ingestive behavior. Appetite 36, 79–83 (2001).

  3. 3.

    et al. Food reward in the absence of taste receptor signaling. Neuron 57, 930–941 (2008).

  4. 4.

    Food for the brain. Cell 161, 9–11 (2015).

  5. 5.

    , , & Independent circuits in the basal ganglia for the evaluation and selection of actions. Proc. Natl. Acad. Sci. USA 110, E3670–E3679 (2013).

  6. 6.

    & Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat. Neurosci. 8, 1481–1489 (2005).

  7. 7.

    & Modulation of striatal projection systems by dopamine. Annu. Rev. Neurosci. 34, 441–466 (2011).

  8. 8.

    Plastic corticostriatal circuits for action learning: what's dopamine got to do with it? Ann. NY Acad. Sci. 1104, 172–191 (2007).

  9. 9.

    , & The evolutionary origin of the vertebrate basal ganglia and its role in action selection. J. Physiol. (Lond.) 591, 5425–5431 (2013).

  10. 10.

    , & Reward-guided learning beyond dopamine in the nucleus accumbens: the integrative functions of cortico-basal ganglia networks. Eur. J. Neurosci. 28, 1437–1448 (2008).

  11. 11.

    , , & Dopaminergic mechanisms in actions and habits. J. Neurosci. 27, 8181–8183 (2007).

  12. 12.

    Dopamine signaling in the dorsal striatum is essential for motivated behaviors: lessons from dopamine-deficient mice. Ann. NY Acad. Sci. 1129, 35–46 (2008).

  13. 13.

    et al. Nutrient selection in the absence of taste receptor signaling. J. Neurosci. 30, 8012–8023 (2010).

  14. 14.

    , & Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron 45, 587–597 (2005).

  15. 15.

    & Taste pathways that mediate accumbens dopamine release by sapid sucrose. Physiol. Behav. 84, 363–369 (2005).

  16. 16.

    et al. Dopamine differentially modulates the excitability of striatal neurons of the direct and indirect pathways in lamprey. J. Neurosci. 33, 8045–8054 (2013).

  17. 17.

    , & Membrane properties of striatal direct and indirect pathway neurons in mouse and rat slices and their modulation by dopamine. PLoS One 8, e57054 (2013).

  18. 18.

    et al. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153, 896–909 (2013).

  19. 19.

    , & A high-throughput screening procedure for identifying mice with aberrant taste and oromotor function. Chem. Senses 27, 461–474 (2002).

  20. 20.

    , & Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat. Neurosci. 15, 816–818 (2012).

  21. 21.

    et al. Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science 330, 385–390 (2010).

  22. 22.

    et al. Concurrent activation of striatal direct and indirect pathways during action initiation. Nature 494, 238–242 (2013).

  23. 23.

    & Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat. Neurosci. 13, 635–641 (2010).

  24. 24.

    , & Relations between movement and single cell discharge in the substantia nigra of the behaving monkey. J. Neurosci. 3, 1599–1606 (1983).

  25. 25.

    & Role of the basal ganglia in the initiation of saccadic eye movements. Prog. Brain Res. 64, 175–190 (1986).

  26. 26.

    & Chemogenetic tools to interrogate brain functions. Annu. Rev. Neurosci. 37, 387–407 (2014).

  27. 27.

    , , , & Taste-independent detection of the caloric content of sugar in Drosophila. Proc. Natl. Acad. Sci. USA 108, 11644–11649 (2011).

  28. 28.

    et al. Layered reward signalling through octopamine and dopamine in Drosophila. Nature 492, 433–437 (2012).

  29. 29.

    et al. Distinct dopamine neurons mediate reward signals for short- and long-term memories. Proc. Natl. Acad. Sci. USA 112, 578–583 (2015).

  30. 30.

    The problem with value. Neurosci. Biobehav. Rev. 43, 259–268 (2014).

  31. 31.

    , & Afferent connections of the parvocellular reticular formation: a horseradish peroxidase study in the rat. Neuroscience 50, 403–425 (1992).

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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


  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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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.

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  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.

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