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Seeing the forest tree by tree: super-resolution light microscopy meets the neurosciences

Nature Neuroscience volume 16, pages 790–797 (2013)Cite this article

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Abstract

Light microscopy can be applied in vivo and can sample large tissue volumes, features crucial for the study of single neurons and neural circuits. However, light microscopy per se is diffraction-limited in resolution, and the substructure of core signaling compartments of neuronal circuits—axons, presynaptic active zones, postsynaptic densities and dendritic spines—can be only insufficiently characterized by standard light microscopy. Recently, several forms of super-resolution light microscopy breaking the diffraction-imposed resolution limit have started to allow highly resolved, dynamic imaging in the cell-biologically highly relevant 10–100 nanometer range ('mesoscale'). New, sometimes surprising answers concerning how protein mobility and protein architectures shape neuronal communication have already emerged. Here we start by briefly introducing super-resolution microscopy techniques, before we describe their use in the analysis of neuronal compartments. We conclude with long-term prospects for super-resolution light microscopy in the molecular and cellular neurosciences.

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Figure 1: Principles of main super-resolution techniques.
Figure 2: Super resolution microscopy reveals the structure of axonal cytoskeleton and active zone cytomatrix of Drosophila synapses.
Figure 3: Dynamic changes in spine morphology and actin distribution.
Figure 4: Examples of single-particle-tracking PALM and three-dimensional STORM imaging.

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Acknowledgements

We would like to thank D. Choquet, T. Kuner and S. Smith for sharing unpublished data and for scientific discussions. We thank T.A. Blanpied, H. Ewers, S. Hell, V. Nägerl, O. Shupliakov and X. Zhuang for permission to use their work. The authors are supported by grants from the Deutsche Forschungsgemeinschaft (TP A3/SFB 958; SI849 7-1).

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  1. Department of Genetics, Institute for Biology, Free University Berlin, Berlin, Germany

    Marta Maglione & Stephan J Sigrist

  2. NeuroCure Cluster of Excellence, Charité Berlin, Berlin, Germany

    Stephan J Sigrist

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Maglione, M., Sigrist, S. Seeing the forest tree by tree: super-resolution light microscopy meets the neurosciences. Nat Neurosci 16, 790–797 (2013). https://doi.org/10.1038/nn.3403

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