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Two types of dopamine neuron distinctly convey positive and negative motivational signals

Nature volume 459, pages 837–841 (2009)Cite this article

Abstract

Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward1,2,3,4. These excitatory responses increase as the reward value increases5. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.

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Figure 1: Pavlovian procedure.
Figure 2: Responses of dopamine neurons to conditioned stimuli.
Figure 3: Responses of dopamine neurons to unconditioned stimuli.
Figure 4: Locations of dopamine neurons in relation to their responses to airpuff-predicting conditioned stimulus.

References

  1. Schultz, W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1–27 (1998)

    Article  CAS  Google Scholar 

  2. Satoh, T., Nakai, S., Sato, T. & Kimura, M. Correlated coding of motivation and outcome of decision by dopamine neurons. J. Neurosci. 23, 9913–9923 (2003)

    Article  CAS  Google Scholar 

  3. Takikawa, Y., Kawagoe, R. & Hikosaka, O. A possible role of midbrain dopamine neurons in short- and long-term adaptation of saccades to position-reward mapping. J. Neurophysiol. 92, 2520–2529 (2004)

    Article  Google Scholar 

  4. Morris, G., Arkadir, D., Nevet, A., Vaadia, E. & Bergman, H. Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons. Neuron 43, 133–143 (2004)

    Article  CAS  Google Scholar 

  5. Tobler, P. N., Fiorillo, C. D. & Schultz, W. Adaptive coding of reward value by dopamine neurons. Science 307, 1642–1645 (2005)

    Article  ADS  CAS  Google Scholar 

  6. Ungless, M. A., Magill, P. J. & Bolam, J. P. Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli. Science 303, 2040–2042 (2004)

    Article  ADS  CAS  Google Scholar 

  7. Chiodo, L. A., Antelman, S. M., Caggiula, A. R. & Lineberry, C. G. Sensory stimuli alter the discharge rate of dopamine (DA) neurons: evidence for two functional types of DA cells in the substantia nigra. Brain Res. 189, 544–549 (1980)

    Article  CAS  Google Scholar 

  8. Coizet, V., Dommett, E. J., Redgrave, P. & Overton, P. G. Nociceptive responses of midbrain dopaminergic neurones are modulated by the superior colliculus in the rat. Neuroscience 139, 1479–1493 (2006)

    Article  CAS  Google Scholar 

  9. Schultz, W. & Romo, R. Responses of nigrostriatal dopamine neurons to high-intensity somatosensory stimulation in the anesthetized monkey. J. Neurophysiol. 57, 201–217 (1987)

    Article  CAS  Google Scholar 

  10. Mantz, J., Thierry, A. M. & Glowinski, J. Effect of noxious tail pinch on the discharge rate of mesocortical and mesolimbic dopamine neurons: selective activation of the mesocortical system. Brain Res. 476, 377–381 (1989)

    Article  CAS  Google Scholar 

  11. Guarraci, F. A. & Kapp, B. S. An electrophysiological characterization of ventral tegmental area dopaminergic neurons during differential Pavlovian fear conditioning in the awake rabbit. Behav. Brain Res. 99, 169–179 (1999)

    Article  CAS  Google Scholar 

  12. Mirenowicz, J. & Schultz, W. Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature 379, 449–451 (1996)

    Article  ADS  CAS  Google Scholar 

  13. Joshua, M., Adler, A., Mitelman, R., Vaadia, E. & Bergman, H. Midbrain dopaminergic neurons and striatal cholinergic interneurons encode the difference between reward and aversive events at different epochs of probabilistic classical conditioning trials. J. Neurosci. 28, 11673–11684 (2008)

    Article  CAS  Google Scholar 

  14. Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599 (1997)

    Article  CAS  Google Scholar 

  15. Montague, P. R., Dayan, P. & Sejnowski, T. J. A framework for mesencephalic dopamine systems based on predictive Hebbian learning. J. Neurosci. 16, 1936–1947 (1996)

    Article  CAS  Google Scholar 

  16. Lynd-Balta, E. & Haber, S. N. The organization of midbrain projections to the striatum in the primate: sensorimotor-related striatum versus ventral striatum. Neuroscience 59, 625–640 (1994)

    Article  CAS  Google Scholar 

  17. Ikemoto, S. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex. Brain Res. Rev. 56, 27–78 (2007)

    Article  CAS  Google Scholar 

  18. Knutson, B., Adams, C. M., Fong, G. W. & Hommer, D. Anticipation of increasing monetary reward selectively recruits nucleus accumbens. J. Neurosci. 21, RC159 (2001)

    Article  CAS  Google Scholar 

  19. Cromwell, H. C. & Schultz, W. Effects of expectations for different reward magnitudes on neuronal activity in primate striatum. J. Neurophysiol. 89, 2823–2838 (2003)

    Article  Google Scholar 

  20. Schultz, W., Apicella, P., Scarnati, E. & Ljungberg, T. Neuronal activity in monkey ventral striatum related to the expectation of reward. J. Neurosci. 12, 4595–4610 (1992)

    Article  CAS  Google Scholar 

  21. Kitama, T., Ohno, T., Tanaka, M., Tsubokawa, H. & Yoshida, K. Stimulation of the caudate nucleus induces contraversive saccadic eye movements as well as head turning in the cat. Neurosci. Res. 12, 287–292 (1991)

    Article  CAS  Google Scholar 

  22. Hikosaka, O., Takikawa, Y. & Kawagoe, R. Role of the basal ganglia in the control of purposive saccadic eye movements. Physiol. Rev. 80, 953–978 (2000)

    Article  CAS  Google Scholar 

  23. Carli, M., Evenden, J. L. & Robbins, T. W. Depletion of unilateral striatal dopamine impairs initiation of contralateral actions and not sensory attention. Nature 313, 679–682 (1985)

    Article  ADS  CAS  Google Scholar 

  24. Holland, P. C. & Gallagher, M. Amygdala circuitry in attentional and representational processes. Trends Cogn. Sci. 3, 65–73 (1999)

    Article  CAS  Google Scholar 

  25. Lin, S. C. & Nicolelis, M. A. Neuronal ensemble bursting in the basal forebrain encodes salience irrespective of valence. Neuron 59, 138–149 (2008)

    Article  CAS  Google Scholar 

  26. Richardson, R. T. & DeLong, M. R. Electrophysiological studies of the functions of the nucleus basalis in primates. Adv. Exp. Med. Biol. 295, 233–252 (1991)

    Article  CAS  Google Scholar 

  27. Matsumoto, M. & Hikosaka, O. Representation of negative motivational value in the primate lateral habenula. Nature Neurosci. 12, 77–84 (2009)

    Article  CAS  Google Scholar 

  28. Matsumoto, M. & Hikosaka, O. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 447, 1111–1115 (2007)

    Article  ADS  CAS  Google Scholar 

  29. Davies, R. M., Gerstein, G. L. & Baker, S. N. Measurement of time-dependent changes in the irregularity of neural spiking. J. Neurophysiol. 96, 906–918 (2006)

    Article  Google Scholar 

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Acknowledgements

We thank S. Hong, E. Bromberg-Martin, M. Yasuda, S. Yamamoto and Y. Tachibana for discussion, M. K. Smith for his histological expertise, J. W. McClurkin, A. M. Nichols, T. W. Ruffner, A. V. Hays and L. P. Jensen for technical assistance, and G. Tansey, D. Parker and B. Nagy for animal care. This research was supported by the Intramural Research Program at the National Institutes of Health, National Eye Institute.

Author Contributions M.M. designed the Pavlovian procedure, performed the experiments and analysed the data. O.H. supported all of these processes. M.M. and O.H. discussed the results and wrote the manuscript.

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Authors and Affiliations

  1. Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-4435, USA ,

    Masayuki Matsumoto & Okihide Hikosaka

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  1. Masayuki Matsumoto
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  2. Okihide Hikosaka
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Corresponding author

Correspondence to Masayuki Matsumoto.

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Matsumoto, M., Hikosaka, O. Two types of dopamine neuron distinctly convey positive and negative motivational signals. Nature 459, 837–841 (2009). https://doi.org/10.1038/nature08028

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