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Wiring specificity in the direction-selectivity circuit of the retina

Nature volume 471, pages 183–188 (2011)Cite this article

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Abstract

The proper connectivity between neurons is essential for the implementation of the algorithms used in neural computations, such as the detection of directed motion by the retina. The analysis of neuronal connectivity is possible with electron microscopy, but technological limitations have impeded the acquisition of high-resolution data on a large enough scale. Here we show, using serial block-face electron microscopy and two-photon calcium imaging, that the dendrites of mouse starburst amacrine cells make highly specific synapses with direction-selective ganglion cells depending on the ganglion cell’s preferred direction. Our findings indicate that a structural (wiring) asymmetry contributes to the computation of direction selectivity. The nature of this asymmetry supports some models of direction selectivity and rules out others. It also puts constraints on the developmental mechanisms behind the formation of synaptic connections. Our study demonstrates how otherwise intractable neurobiological questions can be addressed by combining functional imaging with the analysis of neuronal connectivity using large-scale electron microscopy.

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Figure 1: Functional characterization of DSGCs and their localization within the SBEM volume.
Figure 2: Skeleton reconstructions of DSGCs and SACs.
Figure 3: Contact geometries.
Figure 4: Specificity of SAC outputs.
Figure 5: Specificity of DSGC inputs.
Figure 6: Dendrite-angle distribution.

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Acknowledgements

We thank T. Euler for many useful discussions and help with the functional imaging experiments. We also thank H. Horstmann and S. Mikula for help with staining procedures; J. Kornfeld and F. Svara for programming KNOSSOS; J. Tritthardt for developing electronic circuits and M. Müller for help with the acquisition software; J. Hanne, H. Jakobi and H. Wissler for help with training tracers; M. Feller and Z. J. Zhou for discussion of their results; and J. Bollmann, A. Karpova and S. Seung for comments on the manuscript. We thank N. Abazova, E. Abs, A. Antunes, P. Bastians, M. Beining, J. Buhmann, F. Drawitsch, L. Ehm, F. Isensee, H. Jakobi, S. Kaspar, A. Khan, M. Kiapes, A. Klein, S. Laiouar, E. Möller, J. Trendel, P. Weber, K. Weiß, E. Wiegand and H. Wissler for the tracing work.

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  1. Department of Biomedical Optics, Max Planck Institute for Medical Research, Heidelberg, 69120, Germany

    Kevin L. Briggman, Moritz Helmstaedter & Winfried Denk

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  1. Kevin L. Briggman
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  3. Winfried Denk
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Contributions

K.L.B. and W.D. designed the study; W.D. designed the microtome; K.L.B. performed the calcium imaging and SBEM experiments, K.L.B. and M.H. analysed data; K.L.B., M.H. and W.D. wrote the paper.

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Correspondence to Kevin L. Briggman.

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Competing interests

W.D. receives license income for SBEM technology.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-7 with legends. (PDF 3959 kb)

Supplementary Image Stacks

This zip file contains five small image stacks viewable in ImageJ corresponding to the examples in Figure 3. The centre of the stacks (64,64,64) coincides with the dendritic contact or proximity between a SAC and DSGC. Slice 64 in each stack contains colour-coded dots corresponding to the cell identities in Figure 3. (ZIP 11568 kb)

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Briggman, K., Helmstaedter, M. & Denk, W. Wiring specificity in the direction-selectivity circuit of the retina. Nature 471, 183–188 (2011). https://doi.org/10.1038/nature09818

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