Skilled reaching tasks for head-fixed mice using a robotic manipulandum

Abstract

Skilled forelimb behaviors are among the most important for studying motor learning in multiple species including humans. This protocol describes learned forelimb tasks for mice using a two-axis robotic manipulandum. Our device provides a highly compact adaptation of actuated planar two-axis arms that is simple and inexpensive to construct. This paradigm has been dominant for decades in primate motor neuroscience. Our device can generate arbitrary virtual movement tracks, arbitrary time-varying forces or arbitrary position- or velocity-dependent force patterns. We describe several example tasks permitted by our device, including linear movements, movement sequences and aiming movements. We provide the mechanical drawings and source code needed to assemble and control the device, and detail the procedure to train mice to use the device. Our software can be simply extended to allow users to program various customized movement assays. The device can be assembled in a few days, and the time to train mice on the tasks that we describe ranges from a few days to several weeks. Furthermore, the device is compatible with various neurophysiological techniques that require head fixation.

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Fig. 1: Actuated two-axis rodent manipulandum design and assembly.
Fig. 2: Detailed manipulandum assembly.
Fig. 3: Nested controllers used to operate the manipulandum behavioral experiments.
Fig. 4: Example behavioral tasks, performance and learning.
Fig. 5: Custom LabVIEW software and user interface.

Data availability

An example raw data file is provided in Supplementary Data 1. Additional data are available upon reasonable request.

Code availability

LabVIEW code used for operating the robotic manipulandum is available from GitHub: https://GitHub.com/mjwagner/haptic-for-mice.

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Acknowledgements

M.J.W. is supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. M.J.S. and L.L. are HHMI investigators. This work was supported by NIH and NSF grants.

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Affiliations

Authors

Contributions

M.J.W. and J.S. designed the manipulandum. M.J.W. designed and implemented the electronics and software code for robot control and designed and implemented behavioral tasks and training strategies. T.H.K. designed the mouse-restraining tube and contributed to robot assembly design. M.J.S. and L.L. supervised the project. All authors contributed to the manuscript writing.

Corresponding authors

Correspondence to Mark J. Wagner or Mark J. Schnitzer or Liqun Luo.

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Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Protocols thanks Silvestro Micera and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

Key references using this protocol

Wagner, M. J. et al. Cell 177, 669–682 (2019): https://doi.org/10.1016/j.cell.2019.02.019

Wagner, M. J. et al. Nature 544, 96–100 (2017): https://doi.org/10.1038/nature21726.

Supplementary information

Supplementary Information

Supplementary Fig. 1.

Reporting Summary

Supplementary Video 1

Mouse executing a task in which it is required to reach to one of three target regions (as in Fig. 4e).

Supplementary Data 1

Example raw data set from which Fig. 4f and the right-most panel of Fig. 4g are derived.

Supplementary Data 2

STL files that can be used directly to print the custom manipulandum parts, and the aluminum flange STP file for machining services.

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Wagner, M.J., Savall, J., Kim, T.H. et al. Skilled reaching tasks for head-fixed mice using a robotic manipulandum. Nat Protoc 15, 1237–1254 (2020). https://doi.org/10.1038/s41596-019-0286-8

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