Letter | Published:

Dopamine neuron activity before action initiation gates and invigorates future movements

Nature volume 554, pages 244248 (08 February 2018) | Download Citation

Abstract

Deciding when and whether to move is critical for survival. Loss of dopamine neurons (DANs) of the substantia nigra pars compacta (SNc) in patients with Parkinson’s disease causes deficits in movement initiation and slowness of movement1. The role of DANs in self-paced movement has mostly been attributed to their tonic activity, whereas phasic changes in DAN activity have been linked to reward prediction2,3. This model has recently been challenged by studies showing transient changes in DAN activity before or during self-paced movement initiation4,5,6,7. Nevertheless, the necessity of this activity for spontaneous movement initiation has not been demonstrated, nor has its relation to initiation versus ongoing movement been described. Here we show that a large proportion of SNc DANs, which did not overlap with reward-responsive DANs, transiently increased their activity before self-paced movement initiation in mice. This activity was not action-specific, and was related to the vigour of future movements. Inhibition of DANs when mice were immobile reduced the probability and vigour of future movements. Conversely, brief activation of DANs when mice were immobile increased the probability and vigour of future movements. Manipulations of dopamine activity after movement initiation did not affect ongoing movements. Similar findings were observed for the initiation and execution of learned action sequences. These findings causally implicate DAN activity before movement initiation in the probability and vigour of future movements.

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Acknowledgements

We thank A. Vaz for mouse colony management, I. Vaz for the help during photoidentification experiments, L. Perry for help with stereological cell counts, A. Klaus, P. Zhou, L. Paninski for help with the application of the CNMF-E analysis, and the Champalimaud Hardware Platform (F. Carvalho, A. Silva, D. Bento) for help with the development of the motion sensors. This work was supported by fellowships from Gulbenkian Foundation to J.A.d.S. and Grants from Fundação para a Ciência e Tecnologia, Fronteras de la Ciencia-CONACyT-2022 and the IN226517 DGAPA-PAPIIT-UNAM to F.T. and from ERA-NET, European Research Council (COG 617142), and HHMI (IEC 55007415) to R.M.C.

Author information

Affiliations

  1. Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal

    • Joaquim Alves da Silva
    • , Fatuel Tecuapetla
    • , Vitor Paixão
    •  & Rui M. Costa
  2. Nova Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

    • Joaquim Alves da Silva
    •  & Rui M. Costa
  3. Neuropatologia molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico

    • Fatuel Tecuapetla
  4. Departments of Neuroscience and Neurology, Zuckerman Mind Brain Behavior Institute, Columbia University, New York, New York, USA

    • Rui M. Costa

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Contributions

J.A.d.S. and R.M.C. designed the experiments and analyses and wrote the paper, J.A.d.S. performed all experiments and analyses, F.T. helped with optogenetic and recording experiments, V.P. helped with accelerometer experiments and accelerometer data analyses.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Rui M. Costa.

Reviewer Information Nature thanks D. J. Surmeier and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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https://doi.org/10.1038/nature25457

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