Zentrale Abteilung für Mikroskopie - Imaging Core Facility

Synaptic Architecture (Stigloher)

Research: Synaptic architecture at the nano-scale

Neuronal synapses are highly efficient and complex cellular signaling machineries that achieve remarkable precision in signal transmission for a prolonged period of time, in some cases throughout the lifetime of an animal. The importance of synaptic efficiency is mirrored by many neural diseases but in particular by synaptopathies where synaptic organization and function is disrupted. In order to provide reliable signaling synaptic vesicles have to be retained close to the presynaptic active zone, the domain where vesicles are docked and fuse with the membrane after Ca influx in a nano-domain through voltage gated channels.
How are synaptic vesicles kept coherently close to the active zone to maintain efficient signaling? To shed light onto this question our team focuses on the cellular architecture using a combination of genetic tools and imaging techniques. In particular we apply electron tomography as ultra high 3D resolution method to dissect components and function of synaptic architecture. We use a synergistic combination of two highly tractable models where they are most appropriate: The C. elegans neuromuscular junctions for efficient candidate identification and manipulation and the neuromuscular junctions of the zebrafish larva as vertebrate model to test for evolutionary conservation of function.

2021[ to top ]
  • Britz, S., Markert, S. M., Witvliet, D., Steyer, A. M., Tröger, S., Mulcahy, B., Kollmannsberger, P., Schwab, Y., Zhen, M., & Stigloher, C. Structural Analysis of the Caenorhabditis elegans Dauer Larval Anterior Sensilla by Focused Ion Beam-Scanning Electron Microscopy. Frontiers in Neuroanatomy, 15, 80. https://doi.org/10.3389/fnana.2021.732520
  • Peters, S., Kaiser, L., Fink, J., Schumacher, F., Perschin, V., Schlegel, J., Sauer, M., Stigloher, C., Kleuser, B., Seibel, J., & Schubert-Unkmeir, A. Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria. Scientific Reports, 11(1), 4300-. https://doi.org/10.1038/s41598-021-83813-w
2020[ to top ]
  • Strobel, M., Helmprobst, F., Pauli, M., Heckmann, M., Lillesaar, C., & Stigloher, C. Advancing Array Tomography to Study the Fine Ultrastructure of Identified Neurons in Zebrafish (Danio rerio). Springer Protocols, Neuromethods(155), 59-78. https://link.springer.com/protocol/10.1007%2F978-1-0716-0691-9_4
  • Wen, H., Eckenstein, K., Weihrauch, V., Stigloher, C., & Brehm, P. Primary and secondary motoneurons use different calcium channel types to control escape and swimming behaviors in zebrafish. Proceedings of the National Academy of Sciences, 117(42), 26429-26437. https://doi.org/10.1073/pnas.2015866117
  • Markert, S. M., Skoruppa, M., Yu, B., Mulcahy, B., Zhen, M., Gao, S., Sendtner, M., & Stigloher, C. Overexpression of an {ALS}-associated {FUS} mutation in C. elegans disrupts {NMJ} morphology and leads to defective neuromuscular transmission. Biology Open, 9(12), bio055129. https://doi.org/10.1242/bio.055129
2018[ to top ]
  • D’Alessandro, M., Richard, M., Stigloher, C., Vincent, G., Boulin, T., Richmond, J. E., & Bessereau, J.-L. CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors. ELife, 7(e39649), Article e39649. https://doi.org/10.7554/eLife.39649
  • Kaltdorf, K. V., Theiss, M., Markert, S. M., Zhen, M., Dandekar, T., Stigloher, C., & Kollmannsberger, P. Automated classification of synaptic vesicles in electron tomograms of C. elegans using machine learning. PLOS ONE, 13(10), 1-22. https://doi.org/10.1371/journal.pone.0205348
2017[ to top ]
  • Berger, C., Helmprobst, F., Chapouton, P., Lillesaar, C., & Stigloher, C. sept8a and sept8b mRNA expression in the developing and adult zebrafish. Gene Expression Patterns, 25-26, 8-21. https://doi.org/https://doi.org/10.1016/j.gep.2017.04.002
  • Schieber, N. L., Machado, P., Markert, S. M., Stigloher, C., Schwab, Y., & Steyer, A. M. Chapter 4 - Minimal resin embedding of multicellular specimens for targeted FIB-SEM imaging. In T. Müller-Reichert & P. Verkade (Eds.), Correlative Light and Electron Microscopy III (Vols. 140, pp. 69-83). Academic Press. https://doi.org/https://doi.org/10.1016/bs.mcb.2017.03.005
  • Markert, S. M., Bauer, V., Muenz, T. S., Jones, N. G., Helmprobst, F., Britz, S., Sauer, M., Rössler, W., Engstler, M., & Stigloher, C. Chapter 2 - 3D subcellular localization with superresolution array tomography on ultrathin sections of various species. In T. Müller-Reichert & P. Verkade (Eds.), Correlative Light and Electron Microscopy III (Vols. 140, pp. 21-47). Academic Press. https://doi.org/https://doi.org/10.1016/bs.mcb.2017.03.004
  • Kaltdorf, K. V., Schulze, K., Helmprobst, F., Kollmannsberger, P., Dandekar, T., & Stigloher, C. FIJI Macro 3D ART VeSElecT: 3D Automated Reconstruction Tool for Vesicle Structures of Electron Tomograms. PLOS Computational Biology, 13(1), 1-21. https://doi.org/10.1371/journal.pcbi.1005317
  • Helmprobst, F., Lillesaar, C., & Stigloher, C. Expression of sept3, sept5a and sept5b in the Developing and Adult Nervous System of the Zebrafish (Danio rerio). Frontiers in Neuroanatomy, 11. https://doi.org/10.3389/fnana.2017.00006
2016[ to top ]
  • Markert, S. M., Britz, S., Proppert, S., Lang, M., Witvliet, D., Mulcahy, B., Sauer, M., Zhen, M., Bessereau, J.-L., & Stigloher, C. Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome. Neurophotonics, 3(4), 041802. https://doi.org/10.1117/1.nph.3.4.041802
2015[ to top ]
  • Helmprobst, F., Frank, M., & Stigloher, C. Presynaptic architecture of the larval zebrafish neuromuscular junction. Journal of Comparative Neurology, 523(13), 1984-1997. https://doi.org/10.1002/cne.23775