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A cellular mechanism of reward-related learning

Abstract

Positive reinforcement helps to control the acquisition of learned behaviours. Here we report a cellular mechanism in the brain that may underlie the behavioural effects of positive reinforcement. We used intracranial self-stimulation (ICSS) as a model of reinforcement learning1, in which each rat learns to press a lever that applies reinforcing electrical stimulation to its own substantia nigra2,3. The outputs from neurons of the substantia nigra terminate on neurons in the striatum in close proximity to inputs from the cerebral cortex on the same striatal neurons4. We measured the effect of substantia nigra stimulation on these inputs from the cortex to striatal neurons and also on how quickly the rats learned to press the lever. We found that stimulation of the substantia nigra (with the optimal parameters for lever-pressing behaviour) induced potentiation of synapses between the cortex and the striatum, which required activation of dopamine receptors. The degree of potentiation within ten minutes of the ICSS trains was correlated with the time taken by the rats to learn ICSS behaviour. We propose that stimulation of the substantia nigra when the lever is pressed induces a similar potentiation of cortical inputs to the striatum, positively reinforcing the learning of the behaviour by the rats.

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Figure 1: Intracranial self-stimulation of the nigrostriatal system.
Figure 2: Effect of treatment protocols on corticostriatal responses.
Figure 3: Group average effect of ICSS-like stimulation on corticostriatal responses and cellular properties.
Figure 4: Relationship between changes in synaptic efficacy and ICSS learning and performance.

References

  1. Olds, J. & Milner, P. Positive reinforcement produced by electrical stimulation of septal and other regions of the rat brain. J. Comp. Physiol. Psychol. 47, 419–427 (1954).

    CAS  Article  Google Scholar 

  2. Beninger, R. J., Bellisle, F. & Milner, P. M. Schedule control of behavior reinforced by electrical stimulation of the brain. Science 196, 547–549 (1977).

    ADS  CAS  Article  Google Scholar 

  3. Major, R. & White, N. Memory facilitation by self-stimulation reinforcement mediated by the nigro-neostriatal bundle. Physiol. Behav. 20, 723–733 (1978).

    CAS  Article  Google Scholar 

  4. Smith, A. D. & Bolam, J. P. The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones. Trends Neurosci. 13, 259–265 (1990).

    CAS  Article  Google Scholar 

  5. Schultz, W. Multiple reward signals in the brain. Nature Rev. Neurosci. 1, 199–207 (2000).

    CAS  Article  Google Scholar 

  6. Mirenowicz, J. & Schultz, W. Importance of unpredictability for reward responses in primate dopamine neurons. J. Neurophysiol. 72, 1024–1027 (1994).

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

  8. Matsumoto, N., Hanakawa, T., Maki, S., Graybiel, A. M. & Kimura, M. Role of nigrostriatal dopamine system in learning to perform sequential motor tasks in a predictive manner. J. Neurophysiol. 82, 978–998 (1999).

    CAS  Article  Google Scholar 

  9. Aosaki, T., Graybiel, A. M. & Kimura, M. Effect of the nigrostriatal dopamine system on acquired neural responses in the striatum of behaving monkeys. Science 265, 412–415 (1994).

    ADS  CAS  Article  Google Scholar 

  10. Hodos, W. & Valenstein, E. S. An evaluation of response rate as a measure of rewarding intracranial stimulation. J. Comp. Physiol. Psychol. 55, 80–84 (1962).

    CAS  Article  Google Scholar 

  11. Reynolds, R. W. The relationship between stimulation voltage and rate of hypothalamic self-stimulation in the rat. J. Comp. Physiol. Psychol. 51, 193–198 (1958).

    CAS  Article  Google Scholar 

  12. Wilson, C. J. & Kawaguchi, Y. The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons. J. Neurosci. 16, 2397–2410 (1996).

    CAS  Article  Google Scholar 

  13. Stern, E. A., Jaeger, D. & Wilson, C. J. Membrane potential synchrony of simultaneously recorded striatal spiny neurons in vivo. Nature 394, 475–478 (1998).

    ADS  CAS  Article  Google Scholar 

  14. Wilson, C. J. Postsynaptic potentials evoked in spiny neostriatal projection neurons by stimulation of ipsilateral and contralateral neocortex. Brain Res. 367, 201–213 (1986).

    CAS  Article  Google Scholar 

  15. Reynolds, J. N. J. & Wickens, J. R. Substantia nigra dopamine regulates synaptic plasticity and membrane potential fluctuations in the rat neostriatum, in vivo. Neuroscience 99, 199–203 (2000).

    CAS  Article  Google Scholar 

  16. Wilson, C. J. & Groves, P. M. Spontaneous firing patterns of identified spiny neurons in the rat neostriatum. Brain Res. 220, 67–80 (1981).

    CAS  Article  Google Scholar 

  17. Alexander, G. E. & Crutcher, M. D. Preparation for movement: neural representations of intended direction in three motor areas of the monkey. J. Neurophysiol. 64, 133–150 (1990).

    CAS  Article  Google Scholar 

  18. Kimura, M. Behaviorally contingent property of movement-related activity of the primate putamen. J. Neurophysiol. 63, 1277–1296 (1990).

    CAS  Article  Google Scholar 

  19. Corbett, D. & Wise, R. A. Intracranial self-stimulation in relation to the ascending dopaminergic systems of the midbrain: a moveable electrode mapping study. Brain Res. 185, 1–15 (1980).

    CAS  Article  Google Scholar 

  20. Fibiger, H. C., LePiane, F. G., Jakubovic, A. & Phillips, A. G. The role of dopamine in intracranial self-stimulation of the ventral tegmental area. J. Neurosci. 7, 3888–3896 (1987).

    CAS  Article  Google Scholar 

  21. Wise, R. A. Addictive drugs and brain stimulation reward. Annu. Rev. Neurosci. 19, 319–340 (1996).

    CAS  Article  Google Scholar 

  22. Bielajew, C. & Shizgal, P. Evidence implicating descending fibers in self-stimulation of the medial forebrain bundle. J. Neurosci. 6, 919–929 (1986).

    CAS  Article  Google Scholar 

  23. Swanson, L. W. The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res. Bull. 9, 321–353 (1982).

    CAS  Article  Google Scholar 

  24. Suri, R. E. & Schultz, W. A neural network model with dopamine-like reinforcement signal that learns a spatial delayed response task. Neuroscience 91, 871–890 (1999).

    CAS  Article  Google Scholar 

  25. 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 

  26. Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu. Rev. Neurosci. 9, 357–381 (1986).

    CAS  Article  Google Scholar 

  27. Charpier, S. & Deniau, J. M. In vivo activity-dependent plasticity at cortico-striatal connections: evidence for physiological long-term potentiation. Proc. Natl Acad. Sci. USA 94, 7036–7040 (1997).

    ADS  CAS  Article  Google Scholar 

  28. Miller, R. M. Meaning and Purpose in the Intact Brain 62–120 (Clarendon Press, Oxford, 1981).

    Google Scholar 

  29. Hunt, G. E., Atrens, D. M. & Jackson, D. M. Reward summation and the effects of dopamine D1 and D2 agonists and antagonists on fixed-interval responding for brain stimulation. Pharmacol. Biochem. Behav. 48, 853–862 (1994).

    CAS  Article  Google Scholar 

  30. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic, New York, 1998).

    Google Scholar 

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Acknowledgements

We thank A. Kean and C. Booker for technical assistance. This work was supported by the Health Research Council of New Zealand, Lottery Health Research and the New Zealand Neurological Foundation.

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Correspondence to Jeffery R. Wickens.

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Reynolds, J., Hyland, B. & Wickens, J. A cellular mechanism of reward-related learning. Nature 413, 67–70 (2001). https://doi.org/10.1038/35092560

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