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Brain-wide neuronal dynamics during motor adaptation in zebrafish

Nature volume 485, pages 471–477 (2012)Cite this article

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Abstract

A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.

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Figure 1: Experimental setup and fictive motor adaptation.
Figure 2: Functional imaging during adaptive motor control in larval zebrafish.
Figure 3: Low-dimensional representation of neural network dynamics.
Figure 4: Four types of neural dynamics during adaptive motor control.
Figure 5: Anatomical locations of neurons and neuropil regions.
Figure 6: Effect of inferior olive lesions on visually induced motor adaptation.

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Acknowledgements

We are grateful to D. Schoppik for teaching M.B.A. the fictive swimming preparation, to K.-H. Huang for carrying out spinal calcium green injections, and to M. Concha, R. Baker and L.-H. Ma for advice on anatomy. We thank M. Meister, B. Ölveczky, D. Wolpert, E. Mukamel, M. Yartsev, D. Schoppik, D. Hildebrand, E. Naumann, A. Kampff, P. Latham, T. Dunn and members of the Engert laboratory for useful discussions and comments on the manuscript. We thank P. Oteiza and R. Hellmiss for help with anatomy and figures, and A. Viel for use of laboratory space. M.B.A. thanks D. Wolpert and E. Santos for support. This work was supported by a Sir Henry Wellcome Fellowship from the Wellcome Trust (M.B.A.), a K99 grant no. 5K99NS62780-2 (M.B.O.) and National Institutes of Health grants 5R01EY014429 and RC2NS069407 (F.E.).

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA,

    Misha B. Ahrens, Jennifer M. Li, Drew N. Robson, Alexander F. Schier, Florian Engert & Ruben Portugues

  2. Department of Engineering, Computational and Biological Learning Laboratory, Cambridge University, Trumpington Street, Cambridge CB2 1PZ, UK,

    Misha B. Ahrens

  3. Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Avenida Brasília, Doca de Pedrouços, 1400-038 Lisboa, Portugal ,

    Michael B. Orger

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Contributions

M.B.A. developed the fictive virtual-reality paradigm, carried out the experiments, analysed the data, and built the setup and software. M.B.A., F.E. and R.P. conceived the experiments. M.B.O., D.N.R., J.M.L. and A.F.S. generated the transgenic elavl3:GCaMP2 fish line. M.B.O. generated the transgenic alpha tubulin:C3PA–GFP fish line. All authors discussed the data and the manuscript. M.B.A. wrote the manuscript with the assistance of R.P., M.B.O. and F.E.

Corresponding author

Correspondence to Florian Engert.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text 1-4, Supplementary Figures 1-28 and additional references. (PDF 5762 kb)

Supplementary Movie

This movie shows motor adaptation. In this example, the fish ceases most locomotion during stimulus replay. (MOV 11398 kb)

Supplementary Movie 2

In this movie we see an example of calcium imaging during behavior and it shows the hindbrain including some cerebellum. (MOV 1561 kb)

Supplementary movie 3

This movie shows an example of registration of two-photon imaged plane to reference brain. (MOV 1540 kb)

Supplementary Movie 4

This movie shows anatomy stacks with functional data superimposed as in Fig. 6. (MOV 11524 kb)

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Ahrens, M., Li, J., Orger, M. et al. Brain-wide neuronal dynamics during motor adaptation in zebrafish. Nature 485, 471–477 (2012). https://doi.org/10.1038/nature11057

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