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Connectomic reconstruction of the inner plexiform layer in the mouse retina

Nature volume 500, pages 168174 (08 August 2013) | Download Citation


  • A Corrigendum to this article was published on 15 October 2014


Comprehensive high-resolution structural maps are central to functional exploration and understanding in biology. For the nervous system, in which high resolution and large spatial extent are both needed, such maps are scarce as they challenge data acquisition and analysis capabilities. Here we present for the mouse inner plexiform layer—the main computational neuropil region in the mammalian retina—the dense reconstruction of 950 neurons and their mutual contacts. This was achieved by applying a combination of crowd-sourced manual annotation and machine-learning-based volume segmentation to serial block-face electron microscopy data. We characterize a new type of retinal bipolar interneuron and show that we can subdivide a known type based on connectivity. Circuit motifs that emerge from our data indicate a functional mechanism for a known cellular response in a ganglion cell that detects localized motion, and predict that another ganglion cell is motion sensitive.

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We thank J. Diamond, T. Euler, R. Masland, M. Meister and J. Sanes for discussions, J. Kornfeld and F. Svara for programming and continually improving KNOSSOS, M. Müller and J. Tritthardt for programming and building instrumentation, C. Roome for IT support, and A. Borst, M. Fee, T. Gollisch and A. Karpova for comments on the manuscript. We especially thank F. Isensee for help with synapse identification. We thank P. Bastians, A. Biasotto, F. Drawitsch, H. Falk, A. Gable, M. Grohmann, A. Gäbelein, J. Hanne, F. Isensee, H. Jakobi, M. Kotchourko, E. Möller, J. Pollmann, C. Röhrig, A. Rommerskirchen, L. Schreiber, C. Willburger, H. Wissler and J. Youm for reconstruction management and annotator training, and N. Abazova, S. Abele, O. Aderhold, C. Altbürger, T. Amberger, K. Aninditha, A. Antunes, E. Atsiatorme, H. Augenstein, I. Bartsch, I. Barz, P. Bastians, J. Bauer, H. Bauersachs, R. Bay, J. Becker, M. Beez, S. Bender, M. Berberich, I. Bertlich, J. Bewersdorf, A. Biasotto, P. Biti, M. Bittmann, K. Bretzel, J. Briegel, E. Buckler, A. Buntjer, C. Burkhardt, S. Bühler, S. Daum, N. Demir, E. Demirel, S. Dettmer, M. Diemer, J. Dietrich, S. Dittrich, C. Domnick, F. Drawitsch, C. Eck, L. Ehm, S. Ehrhardt, T. Eliguezel, K. Ernst, O. Eryilmaz, F. Euler, H. Falk, K. Fischer, K. Foerster, R. Foitzik, A. Foltin, R. Foltin, S. Freiß, A. Gable, P. Gallandi, K. Garbe, A. Gebhardt, F. Gebhart, S. Gottwalt, A. Greis, M. Grohmann, A. Gromann, S. Gröbner, E. Grün, M. Grün, K. Guo, A. Gäbelein, K. Haase, J. Hammerich, J. Hanne, B. Hauber, M. Hensen, F. Hentzschel, M. Herberz, M. Heumannskämper, C. Hilbert, L. Hofmann, P. Hofmann, T. Hondrich, U. Häusler, M. Höreth, J. Hügle, F. Isensee, A. Ivanova, F. Jahnke, H. Jakobi, M. Joel, M. Jonczyk, A. Joschko, A. Jünger, K. Kappler, S. Kaspar, C. Kehrel, J. Kern, K. Keßler, S. Khoury, M. Kiapes, M. Kirchberger, A. Klein, C. Klein, S. Klein, J. Kratzer, C. Kraut, P. Kremer, P. Kretzer, F. Kröller, D. Krüger, M. Kuderer, S. Kull, S. Kwakman, S. Laiouar, L. Lebelt, H. Lesch, R. Lichtenberger, J. Liermann, C. Lieven, J. Lin, B. Linser, S. Lorger, J. Lott, D. Luft, L. Lust, J. Löffler, C. Marschall, B. Martin, D. Maton, B. Mayer, S. Mayorca, de. Ituarte, M. Meleux, C. Meyer, M. Moll, T. Moll, L. Mroszewski, E. Möller, M. Müller, L. Münster, N. Nasresfahani, J. Nassal, M. Neuschwanger, C. Nguyen, J. Nguyen, N. Nitsche, S. Oberrauch, F. Obitz, D. Ollech, C. Orlik, T. Otolski, S. Oumohand, A. Palfi, J. Pesch, M. Pfarr, S. Pfarr, M. Pohrath, J. Pollmann, M. Prokscha, S. Putzke, E. Rachmad, M. Reichert, J. Reinhardt, M. Reitz, J. Remus, M. Richter, M. Richter, J. Ricken, N. Rieger, F. Rodriguez. Jahnke, A. Rommerskirchen, M. Roth, I. Rummer, J. Rätzer, C. Röhrig, J. Röther, V. Saratov, E. Sauter, T. Schackel, M. Schamberger, M. Scheller, J. Schied, M. Schiedeck, J. Schiele, K. Schleich, M. Schlösser, S. Schmidt, C. Schneeweis, K. Schramm, M. Schramm, L. Schreiber, D. Schwarz, A. Schürholz, L. Schütz, A. Seitz, C. Sellmann, E. Serger, J. Sieber, L. Silbermann, I. Sonntag, T. Speck, Y. Söhngen, T. Tannig, N. Tisch, V. Tran, J. Trendel, M. Uhrig, D. Vecsei, F. Viehweger, V. Viehweger, R. Vogel, A. Vogel, J. Volz, P. Weber, K. Wegmeyer, J. Wiederspohn, E. Wiegand, R. Wiggers, C. Willburger, H. Wissler, V. Wissdorf, S. Wörner, J. Youm, A. Zegarra, J. Zeilfelder, F. Zickgraf and T. Ziegler for cell reconstruction. This work was supported by the Max-Planck Society and the DFG (Leibniz prize to W.D.). H.S.S. is grateful for support from the Gatsby Charitable Foundation.

Author information

Author notes

    • Moritz Helmstaedter
    • , Kevin L. Briggman
    • , Srinivas C. Turaga
    •  & Viren Jain

    Present addresses: Max-Planck Institute of Neurobiology, D-82152 Martinsried, Germany (M.H.); National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA (K.L.B.); Gatsby Computational Neuroscience Unit, London WC1N 3AR, UK (S.C.T.); Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147, USA (V.J.).


  1. Max-Planck Institute for Medical Research, D-69120 Heidelberg, Germany

    • Moritz Helmstaedter
    • , Kevin L. Briggman
    •  & Winfried Denk
  2. Department of Brain and Cognitive Sciences, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Srinivas C. Turaga
    • , Viren Jain
    •  & H. Sebastian Seung


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M.H. and W.D. designed the study. K.L.B. prepared the samples and acquired the data using a microtome designed by W.D. M.H. analysed the data, with minor contributions from W.D. S.C.T., V.J. and H.S.S. developed the boundary classifier. M.H., K.L.B. and W.D. wrote the paper.

Competing interests

W.D. receives licensing income from Gatan Inc.

Corresponding author

Correspondence to Moritz Helmstaedter.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains full descriptions of Supplementary Data sets 1-8.

  2. 2.

    Supplementary Data

    This file contains Supplementary Data 1, a gallery of cell types, depth profiles, and contact area plots (see Supplementary Information for detailed description).

Zip files

  1. 1.

    Supplementary Data

    This zipped file contains Supplementary Data files 2, 4, 5, 7 and 8 (see Supplementary Information for detailed description).

  2. 2.

    Supplementary Data

    This zipped file contains Supplementary Data files 3a and b, which contain volume data samples from the conventionally stained sample (see Supplementary Information for detailed description).

  3. 3.

    Supplementary Data

    This zipped file contains Supplementary Data files 3c, d and e containing volume data samples of EM data from the main data set (e2006), X-direction component of the classifier output for the same region, and segmentation before skeleton-based object collection (see Supplementary Information for detailed description).

  4. 4.

    Supplementary Data

    This zipped file contains Supplementary Data 6 a and b, 6a contains a gallery of 36 Ganglion cells, 6b contains Gallery of 190 small-field Amacrine cells (see Supplementary Information for detailed description).

  5. 5.

    Supplementary Data

    This zipped file contains Supplementary Data 6c, which contains a gallery of 163 medium- and wide-field Amacrine cells (see Supplementary Information for detailed description).

  6. 6.

    Supplementary Data

    This zipped file contains Supplementary Data 6d which contains a gallery of 307 cone bipolar cells (see Supplementary Information for detailed description).

  7. 7.

    Supplementary Data

    This zipped file contains Supplementary Data 6e and f, 6e contains a gallery of 144 rod bipolar cells and 6f contains a gallery of 110 cells from the “orphan” category (see Supplementary Information for detailed description).

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