Technical Report

An interactive framework for whole-brain maps at cellular resolution

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Abstract

To deconstruct the architecture and function of brain circuits, it is necessary to generate maps of neuronal connectivity and activity on a whole-brain scale. New methods now enable large-scale mapping of the mouse brain at cellular and subcellular resolution. We developed a framework to automatically annotate, analyze, visualize and easily share whole-brain data at cellular resolution, based on a scale-invariant, interactive mouse brain atlas. This framework enables connectivity and mapping projects in individual laboratories and across imaging platforms, as well as multiplexed quantitative information on the molecular identity of single neurons. As a proof of concept, we generated a comparative connectivity map of five major neuron types in the corticostriatal circuit, as well as an activity-based map to identify hubs mediating the behavioral effects of cocaine. Thus, this computational framework provides the necessary tools to generate brain maps that integrate data from connectivity, neuron identity and function.

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Acknowledgements

D.F. thanks J. Bernardi and J.H. Lee for fruitful discussions about the software or the paper. K.M. acknowledges financial support from the Swedish Research Council (VR 2012-02049), from the Karolinska Institutet (KID-funding supporting D.F., O.T., A.M.), from the Strategic Neuroscience Area at Karolinska Institutet (StratNeuro) for rabies virus production and from the Swedish Brain Foundation (Hjärnfonden). Additional financial support for the project was from a National Institute of Mental Health grant (MH109795 to G.R., K.M. and C.A.M.) and a National Institute on Drug Abuse grant (DA0036376, to C.A.M.).

Author information

Author notes

  1. Daniel Fürth and Konstantinos Meletis contributed equally to this work

Affiliations

  1. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

    • Daniel Fürth
    • , Ourania Tzortzi
    • , Yang Xuan
    • , Antje Märtin
    • , Iakovos Lazaridis
    • , Giada Spigolon
    • , Gilberto Fisone
    • , Marie Carlén
    •  & Konstantinos Meletis
  2. Department of Neuroscience, Scripps Research Institute, Jupiter, FL, USA

    • Thomas Vaissière
    • , Courtney A. Miller
    •  & Gavin Rumbaugh
  3. Department of Bioengineering, Stanford University, Stanford, CA, USA

    • Raju Tomer
    •  & Karl Deisseroth
  4. Department of Molecular Medicine, Scripps Research Institute, Jupiter, FL, USA

    • Courtney A. Miller

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Contributions

D.F. conceived and developed the computational framework, performed experiments and contributed to data collection, analyzed data and wrote the paper. T.V. contributed to the computational framework, performed experiments, collected data and contributed to writing of the paper. O.T., Y.X., A.M., I.L. and G.S. performed experiments and contributed to data collection. G.F. supervised experiments on corticostriatal tracing. R.T. and K.D. developed and performed COLM experiments. M.C. supervised experiments and contributed to writing of the paper. C.A.M. supervised experiments and contributed to the computational framework and to writing of the paper. G.R. supervised experiments and contributed to the computational framework and to writing of the paper. K.M. conceived and supervised the project and wrote the paper.

Competing interests

D.F. is a stakeholder in Histohub AB. The other authors declare no competing financial interests.

Corresponding author

Correspondence to Konstantinos Meletis.

Integrated Supplementary Information

Supplementary information

  1. Supplementary Text and Figures

    Supplementary Figures 1–11 and Supplementary Table 1

  2. Life Sciences Reporting Summary

    N/A

  3. Supplementary Table 1

    N/A

  4. Supplementary Video 1 – 3D reconstruction of sectioned tissue form a single mouse brain

    Green cells are presynaptic partners to D2-expressing striatal neurons labeled using monosynaptic cell-type specific rabies-EGFP virus in D2-cre mouse

  5. Supplementary Video 2 – 3D reconstruction of 161,294 neurons from five different mice

    Initially labeled neurons are color coded according to brain region, later (00:18) neurons are color coded according to transgenic mouse line (dark blue: D1-Cre, red: D2-Cre, light blue: Chat-Cre, yellow: Camk2a-Cre, green: Gad2-Cre)