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Connectomic reconstruction of the inner plexiform layer in the mouse retina

Nature volume 500, pages 168–174 (2013)Cite this article

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A Corrigendum to this article was published on 15 October 2014

Abstract

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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Figure 1: Raw data, skeletons and bipolar cell analysis.
Figure 2: Ganglion and amacrine cells.
Figure 3: Automatic segmentation and contact detection.
Figure 4: Contact matrices.
Figure 5: CBC5 subtypes.
Figure 6: Circuits originating from the XBC and ON/OFF cells.

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Acknowledgements

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.

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Author notes

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

    Present address: 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.).,

Authors and Affiliations

  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, 02139, Massachusetts, USA

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

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Contributions

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.

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Correspondence to Moritz Helmstaedter.

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W.D. receives licensing income from Gatan Inc.

Supplementary information

Supplementary Information

This file contains full descriptions of Supplementary Data sets 1-8. (PDF 523 kb)

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). (PDF 27686 kb)

Supplementary Data

This zipped file contains Supplementary Data files 2, 4, 5, 7 and 8 (see Supplementary Information for detailed description). (ZIP 26213 kb)

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). (ZIP 27921 kb)

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). (ZIP 27295 kb)

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). (ZIP 22023 kb)

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). (ZIP 16569 kb)

Supplementary Data

This zipped file contains Supplementary Data 6d which contains a gallery of 307 cone bipolar cells (see Supplementary Information for detailed description). (ZIP 26832 kb)

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). (ZIP 21656 kb)

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Helmstaedter, M., Briggman, K., Turaga, S. et al. Connectomic reconstruction of the inner plexiform layer in the mouse retina. Nature 500, 168–174 (2013). https://doi.org/10.1038/nature12346

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