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The honeycomb maze provides a novel test to study hippocampal-dependent spatial navigation

Nature volume 554, pages 102105 (01 February 2018) | Download Citation

Abstract

Here we describe the honeycomb maze, a behavioural paradigm for the study of spatial navigation in rats. The maze consists of 37 platforms that can be raised or lowered independently. Place navigation requires an animal to go to a goal platform from any of several start platforms via a series of sequential choices. For each, the animal is confined to a raised platform and allowed to choose between two of the six adjacent platforms, the correct one being the platform with the smallest angle to the goal-heading direction. Rats learn rapidly and their choices are influenced by three factors: the angle between the two choice platforms, the distance from the goal, and the angle between the correct platform and the direction of the goal. Rats with hippocampal damage are impaired in learning and their performance is affected by all three factors. The honeycomb maze represents a marked improvement over current spatial navigation tests, such as the Morris water maze1,2,3, because it controls the choices of the animal at each point in the maze, provides the ability to assess knowledge of the goal direction from any location, enables the identification of factors influencing task performance and provides the possibility for concomitant single-cell recording.

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Acknowledgements

We thank M. Bertelli, A. Hastings, D. Howett, N. Khan, P. Mumford, A. O’Leary, B. Potter, S. Richards and R. Wu for their contribution to this work, and D. Farquharson and D. Halpin for their input to the design, building and testing of maze prototypes. This work was supported by grants from the Wellcome Trust and the Gatsby Charitable Foundation to J.O. R.A.W. is an MRC Clinical Research Training Fellow, J.K. is a Wellcome Trust/Royal Society Sir Henry Dale Fellow and is supported by the Kavli Foundation Dream Team project and the Isaac Newton Trust. D.C. is funded by the Cambridge NIHR Biomedical Research Centre and by the Wellcome Trust.

Author information

Author notes

    • Ruth A. Wood
    • , Marius Bauza
    •  & Julija Krupic

    These authors contributed equally to this work.

Affiliations

  1. Sainsbury Wellcome Centre, UCL, London W1T 4JG, UK

    • Ruth A. Wood
    • , Marius Bauza
    • , Stephen Burton
    •  & John O’Keefe
  2. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK

    • Julija Krupic
  3. Cell & Developmental Biology, UCL, London WC1E 6BT, UK

    • Julija Krupic
    •  & John O’Keefe
  4. DZNE German Centre for Neurodegenerative Diseases, Bonn 53127, Germany

    • Andrea Delekate
  5. Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 2PY, UK

    • Dennis Chan

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Contributions

J.O. conceived the maze and the study. J.O., M.B., J.K. and S.B. were instrumental in designing, building and testing prototypes of the maze. J.K. and M.B. designed the custom-made software used to operate the maze. R.A.W. designed testing schedule 1 for the control experiment, and A.D. and J.O. designed testing schedule 2 for the lesion experiment. A.D. and S.B. performed the hippocampal lesion and sham lesion surgeries. R.A.W. acquired the behavioural data. R.A.W. and A.D. performed the histology for the lesion experiment, and R.A.W. measured hippocampal lesion volumes. R.A.W. conducted the data management and performed the statistical analyses. J.K., S.B. and J.O. collected the single-unit data and J.K. and J.O. analysed these data. J.O. and R.A.W. wrote the manuscript, with contributions to later drafts from all other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John O’Keefe.

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    Supplementary Information

    This file contains a Supplementary Discussion and additional references.

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    Life Sciences Reporting Summary

Videos

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    Control rat navigating the Honeycomb Maze

    A control rat making a series of choices as it navigates to the goal on the Honeycomb Maze.

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https://doi.org/10.1038/nature25433

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