Article

Brain-wide neuronal dynamics during motor adaptation in zebrafish

  • Nature volume 485, pages 471477 (24 May 2012)
  • doi:10.1038/nature11057
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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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References

  1. 1.

    , & Dorsal horn cells in spinal and in freely moving rats. Exp. Neurol. 19, 519–529 (1967)

  2. 2.

    et al. High-speed, miniaturized fluorescence microscopy in freely moving mice. Nature Methods 5, 935–938 (2008)

  3. 3.

    , , , & Monitoring neural activity with bioluminescence during natural behavior. Nature Neurosci. 13, 513–520 (2010)

  4. 4.

    , , , & Functional imaging of hippocampal place cells at cellular resolution during virtual navigation. Nature Neurosci. 13, 1433–1440 (2010)

  5. 5.

    , & Active flight increases the gain of visual motion processing in Drosophila. Nature Neurosci. 13, 393–399 (2010)

  6. 6.

    et al. Two-photon calcium imaging from head-fixed Drosophila during optomotor walking behavior. Nature Methods 7, 535–540 (2010)

  7. 7.

    , , & Visual control of flight speed in Drosophila melanogaster. J. Exp. Biol. 212, 1120–1130 (2009)

  8. 8.

    Short-term learning during flight control in Locusta migratoria. J. Comp. Physiol. 163, 803–812 (1988)

  9. 9.

    , , , & Can a fly ride a bicycle? Phil. Trans. R. Soc. Lond. B 337, 261–269 (1992)

  10. 10.

    , , & Learning and memory in the vestibulo-ocular reflex. Annu. Rev. Neurosci. 18, 409–441 (1995)

  11. 11.

    , & The cerebellum: a neuronal learning machine? Science 272, 1126–1131 (1996)

  12. 12.

    & Purkinje cell activity during motor learning. Brain Res. 128, 309–328 (1977)

  13. 13.

    & Bayesian integration in sensorimotor learning. Nature 427, 244–247 (2004)

  14. 14.

    & Adaptive locomotor behavior in larval zebrafish. Front. Syst. Neurosci. 5, 72 (2011)

  15. 15.

    & The optomotor response and induced motion of the self. Perception 15, 497–502 (1986)

  16. 16.

    , , & Perception of Fourier and non-Fourier motion by larval zebrafish. Nature Neurosci. 3, 1128–1133 (2000)

  17. 17.

    , , & Evidence for a widespread brain stem escape network in larval zebrafish. J. Neurophysiol. 87, 608–614 (2002)

  18. 18.

    , , , & Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex. Nature 433, 597–603 (2005)

  19. 19.

    , & Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990)

  20. 20.

    , , & Imaging neuronal activity during zebrafish behavior with a genetically encoded calcium indicator. J. Neurophysiol. 90, 3986–3997 (2003)

  21. 21.

    et al. Filtering of visual information in the tectum by an identified neural circuit. Science 330, 669–673 (2010)

  22. 22.

    , , , & Escape behavior elicited by single, channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons. Curr. Biol. 18, 1133–1137 (2008)

  23. 23.

    and Drapeau, P. Interaction between hindbrain and spinal networks during the development of locomotion in zebrafish. Dev. Neurobiol. 67, 933–947 (2007)

  24. 24.

    , , , & Control of visually guided behavior by distinct populations of spinal projection neurons. Nature Neurosci. 11, 327–333 (2008)

  25. 25.

    , & Imaging the functional organization of zebrafish hindbrain segments during escape behaviors. Neuron 17, 1145–1155 (1996)

  26. 26.

    , , , & Imaging large-scale neural activity with cellular resolution in awake, mobile mice. Neuron 56, 43–57 (2007)

  27. 27.

    & Fictive swimming motor patterns in wild type and mutant larval zebrafish. J. Neurophysiol. 93, 3177–3188 (2005)

  28. 28.

    & The neuronal correlate of locomotion in fish. “fictive swimming” induced in an in vitro preparation of the lamprey spinal cord. Exp. Brain Res. 41, 11–18 (1980)

  29. 29.

    et al. Imaging cellular signals in the heart in vivo: cardiac expression of the high-signal Ca2+ indicator GCaMP2. Proc. Natl Acad. Sci. USA 103, 4753–4758 (2006)

  30. 30.

    et al. Analysis of upstream elements in the HuC promoter leads to the establishment of transgenic zebrafish with fluorescent neurons. Dev. Biol. 227, 279–293 (2000)

  31. 31.

    , , & Visual influence on rabbit horizontal vestibulo-ocular reflex presumably effected via the cerebellar flocculus. Brain Res. 65, 170–174 (1974)

  32. 32.

    & Transient dynamics versus fixed points in odor representations by locust antennal lobe projection neurons. Neuron 48, 661–673 (2005)

  33. 33.

    , , , & Transformation of odor representations in target areas of the olfactory bulb. Nature Neurosci. 12, 474–482 (2009)

  34. 34.

    et al. A structural and functional ground plan for neurons in the hindbrain of zebrafish. Proc. Natl Acad. Sci. USA 108, 1164–1169 (2011)

  35. 35.

    , , , & Mapping a sensory-motor network onto a structural and functional ground plan in the hindbrain. Proc. Natl Acad. Sci. USA 108, 1170–1175 (2011)

  36. 36.

    et al. Anatomy of zebrafish cerebellum and screen for mutations affecting its development. Dev. Biol. 330, 406–426 (2009)

  37. 37.

    et al. Proneural gene-linked neurogenesis in zebrafish cerebellum. Dev. Biol. 343, 1–17 (2010)

  38. 38.

    , , , & The zebrafish cerebellar upper rhombic lip generates tegmental hindbrain nuclei by long-distance migration in an evolutionary conserved manner. J. Comp. Neurol. 518, 2794–2817 (2010)

  39. 39.

    , & Neuroanatomy of the Zebrafish Brain: a Topological Atlas (Birkhäuser, 1996)

  40. 40.

    A theory of cerebellar cortex. J. Physiol. 202, 437–470 (1969)

  41. 41.

    A theory of cerebellar function. Math. Biosci. 10, 25–61 (1971)

  42. 42.

    & Active reversal of motor memories reveals rules governing memory encoding. Neuron 39, 1031–1042 (2003)

  43. 43.

    , & Effects of partial ablation of the cerebellum on sustained swimming in goldfish. Brain Behav. Evol. 70, 105–114 (2007)

  44. 44.

    , & The influence of cerebellar lesions on the swimming performance of the trout. J. Exp. Biol. 167, 171–178 (1992)

  45. 45.

    & Cerebellar-dependent learning in larval zebrafish. J. Neurosci. 31, 8708–8712 (2011)

  46. 46.

    , , & Mosaic hoxb4a neuronal pleiotropism in zebrafish caudal hindbrain. PloS ONE 4, e5944 (2009)

  47. 47.

    et al. Microcircuitry and function of the inferior olive. Trends Neurosci. 21, 391–400 (1998)

  48. 48.

    et al. Spatial gradients and multidimensional dynamics in a neural integrator circuit. Nature Neurosci. 14, 1150–1159 (2011)

  49. 49.

    Temperature and muscle. J. Exp. Biol. 115, 333–344 (1985)

  50. 50.

    , , , , & A dimorphic pheromone circuit in Drosophila from sensory input to descending output. Nature 468, 686–690 (2010)

  51. 51.

    , , & Induction of α1-tubulin gene expression during development and regeneration of the fish central nervous system. J. Neurobiol. 37, 429–440 (1998)

  52. 52.

    , & Automated analysis of cellular signals from large-scale calcium imaging data. Neuron 63, 747–760 (2009)

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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.).

Author information

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. Computational and Biological Learning Laboratory, Department of Engineering, 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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Florian Engert.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Text 1-4, Supplementary Figures 1-28 and additional references.

Videos

  1. 1.

    Supplementary Movie

    This movie shows motor adaptation. In this example, the fish ceases most locomotion during stimulus replay.

  2. 2.

    Supplementary Movie 2

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

  3. 3.

    Supplementary movie 3

    This movie shows an example of registration of two-photon imaged plane to reference brain.

  4. 4.

    Supplementary Movie 4

    This movie shows anatomy stacks with functional data superimposed as in Fig. 6.

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