Cortical remodelling induced by activity of ventral tegmental dopamine neurons


Representations of sensory stimuli in the cerebral cortex can undergo progressive remodelling according to the behavioural importance of the stimuli1,2. The cortex receives widespread projections from dopamine neurons in the ventral tegmental area (VTA)3,4,5, which are activated by new stimuli or unpredicted rewards6,7, and are believed to provide a reinforcement signal for such learning-related cortical reorganization8. In the primary auditory cortex (AI) dopamine release has been observed during auditory learning that remodels the sound-frequency representations9,10. Furthermore, dopamine modulates long-term potentiation11,12, a putative cellular mechanism underlying plasticity13. Here we show that stimulating the VTA together with an auditory stimulus of a particular tone increases the cortical area and selectivity of the neural responses to that sound stimulus in AI. Conversely, the AI representations of nearby sound frequencies are selectively decreased. Strong, sharply tuned responses to the paired tones also emerge in a second cortical area, whereas the same stimuli evoke only poor or non-selective responses in this second cortical field in naive animals. In addition, we found that strong long-range coherence of neuronal discharge emerges between AI and this secondary auditory cortical area.

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Figure 1: Representative cortical tonotopic best frequency maps and frequency-intensity receptive fields.
Figure 2: Reorganization of the auditory cortex by VTA microstimulation paired with a 9-kHz pulsed tone.
Figure 3: VTA/tone-pairing increases neuronal synchrony between the ventroposterior region and the 9-kHz-representing AI area.
Figure 4: VTA stimulation effects are temporally asymmetrical.


  1. 1

    Buonomano, D. V. & Merzenich, M. M. Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998).

    CAS  Article  Google Scholar 

  2. 2

    Sanes, J. N. & Donoghue, J. P. Plasticity and primary motor cortex. Annu. Rev. Neurosci. 23, 393–415 (2000).

    CAS  Article  Google Scholar 

  3. 3

    Foote, S. L. & Morrison, J. H. Extrathalamic modulation of cortical function. Annu. Rev. Neurosci. 10, 67–95 (1987).

    CAS  Article  Google Scholar 

  4. 4

    Goldsmith, S. K. & Joyce, J. N. Dopamine D2 receptors are organized in bands in normal human temporal cortex. Neurosci. 74, 435–451 (1996).

    CAS  Article  Google Scholar 

  5. 5

    Lidow, M. S., Goldman-Rakic, P. S., Gallager, D. W. & Rakic, P. Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using (3H)raclopride, (3H)spiperone and (3H)SCH23390. Neruoscience 40, 657–671 (1991).

    CAS  Article  Google Scholar 

  6. 6

    Hollerman, J. R. & Schultz, W. Dopamine neurons report an error in the temporal prediction of reward during learning. Nature Neurosci. 1, 304–309 (1998).

    CAS  Article  Google Scholar 

  7. 7

    Schultz, W. & Dickinson, A. Neuronal coding of prediction errors. Annu. Rev. Neurosci. 23, 473–500 (2000).

    CAS  Article  Google Scholar 

  8. 8

    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).

    CAS  Article  Google Scholar 

  9. 9

    Stark, H. & Scheich, H. Dopaminergic and serotonergic neurotransmission systems are differentially involved in auditory cortex learning: a long-term microdialysis study of metabolites. J. Neurochem. 68, 691–697 (1997).

    CAS  Article  Google Scholar 

  10. 10

    Bakin, J. S., South, D. A. & Weinberger, N. M. Induction of receptive field plasticity in the auditory cortex of the guinea pig during instrumental avoidance conditioning. Behav. Neurosci. 110, 905–913 (1996).

    CAS  Article  Google Scholar 

  11. 11

    Gurden, H., Takita, M. & Jay, T. M. Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex synapses in vivo. J. Neurosci. 20, RC106, 1–5 (2000)..

    CAS  Article  Google Scholar 

  12. 12

    Otmakhova, N. A. & Lisman, J. E. D1/D5 dopamine receptors inhibit depotentiation at CA1 synapses via cAMP-dependent mechanism. J. Neurosci. 18, 1270–1279 (1998).

    CAS  Article  Google Scholar 

  13. 13

    Rioult-Pedotti, M.-S., Friedman, D. & Donoghue, J. P. Learning-induced LTP in neocortex. Science 290, 533–536 (2000).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Kilgard, M. P. & Merzenich, M. M. Cortical map reorganization enabled by nucleus basalis activity. Science 279, 1714–1718 (1998).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Zilles, K. in The Cerebral Cortex of the Rat (eds Kolb, B. & Tees, R. C.) 77–112 (MIT, Cambridge, Massachusetts, 1990).

    Google Scholar 

  16. 16

    Pandya, D. N. & Seltzer, B. Association areas of the cerebral cortex. Trends Neurosci. 5, 386–390 (1982).

    Article  Google Scholar 

  17. 17

    Singer, W. Neuronal synchrony: a versatile code for the definition of relations? Neuron 24, 49–65 (1999).

    CAS  Article  Google Scholar 

  18. 18

    Engel, A. K., König, P., Kreiter, A. K. & Singer, W. Interhemispheric synchronization of oscillatory neuronal responses in cat visual cortex. Science 252, 1177–1179 (1991).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Traub, R. D., Whittington, M. A., Stanford, I. M. & Jefferys, J. G. A mechanism for generation of long-range synchronous fast oscillations in the cortex. Nature 383, 621–624 (1996).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Oades, R. D. & Halliday, G. M. Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res. 434, 117–165 (1987).

    CAS  Article  Google Scholar 

  21. 21

    Haring, J. H. & Wang, R. Y. The identification of some sources of afferent input to the rat nucleus basalis magnocellularis by retrograde transport of horseradish peroxidase. Brain Res. 366, 152–158 (1986).

    CAS  Article  Google Scholar 

  22. 22

    Kilgard, M. P. & Merzenich, M. M. Plasticity of temporal information processing in the primary auditory cortex. Nature Neursci. 1, 727–731 (1998).

    CAS  Article  Google Scholar 

  23. 23

    Bakin, J. S. & Weinberger, N. M. Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis. Proc. Natl Acad. Sci. USA 93, 11219–11224 (1996).

    ADS  CAS  Article  Google Scholar 

  24. 24

    Van Essen, D. C., Anderson, C. H. & Felleman, D. J. Information processing in the primate visual system: an integrated systems perspective. Science 255, 419–423 (1992).

    ADS  CAS  Article  Google Scholar 

  25. 25

    Tremblay, N., Warren, R. A. & Dykes, R. W. Electrophysiological studies of acetylcholine and the role of the basal forebrain in the somatosensory cortex of the cat. II. Cortical neurons excited by somatic stimuli. J. Neurophysiol. 64, 1212–1222 (1990).

    CAS  Article  Google Scholar 

  26. 26

    Sachdev, R. N., Lu, S. M., Wiley, R. G. & Ebner, F. F. Role of the basal forebrain cholinergic projection in somatosensory cortical plasticity. J. Neurophysiol. 79, 3216–3228 (1998).

    CAS  Article  Google Scholar 

  27. 27

    Jenkins, W. M., Merzenich, M. M., Ochs, M. T., Allard, T. & Guic-Robles, E. Functional reorganization of primary somatosensory cortex in adult owl monkeys after behaviorally controlled tactile stimulation. J. Neurophysiol. 63, 82–104 (1990).

    CAS  Article  Google Scholar 

  28. 28

    Recanzone, G. H., Schreiner, C. E. & Merzenich, M. M. Plasticity in the frequency representation of primary auditory cortex following discrimination training in adult owl monkeys. J. Neurosci. 13, 87–103 (1993).

    CAS  Article  Google Scholar 

  29. 29

    Nudo, R. J., Wise, B. M., SiFuentes, F. & Milliken, G. W. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science 272, 1791–1794 (1996).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Diamond, D. M. & Weinberger, N. M. Classical conditioning rapidly induces specific changes in frequency receptive fields of single neurons in secondary and ventral ectosylvian auditory cortical fields. Brain Res. 372, 357–360 (1986).

    CAS  Article  Google Scholar 

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We thank D. Blake for many informative suggestions; L. I. Zhang and F. Strata for discussions; and C. Garabedian and T. Moallem for comments on the manuscript. This work was supported by an NIH grant, the Coleman Fund, the Mental Insight Foundation, and Hearing Research.

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Correspondence to Michael M. Merzenich.

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Bao, S., Chan, V. & Merzenich, M. Cortical remodelling induced by activity of ventral tegmental dopamine neurons. Nature 412, 79–83 (2001).

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