A Versatile Synthetic Affinity Probe Reveals Inhibitory Synapse Ultrastructure and Brain Connectivity**

Vladimir Khayenko, Clemens Schulte, Sara L. Reis, Orly Avraham, Cataldo Schietroma, Rafael Worschech, Noah F. Nordblom, Sonja Kachler, Carmen Villmann, Katrin G. Heinze, Andreas Schlosser, Ora Schueler-Furman, Philip Tovote, Christian G. Specht*, Hans M. Maric*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Visualization of inhibitory synapses requires protocol tailoring for different sample types and imaging techniques, and usually relies on genetic manipulation or the use of antibodies that underperform in tissue immunofluorescence. Starting from an endogenous ligand of gephyrin, a universal marker of the inhibitory synapse, we developed a short peptidic binder and dimerized it, significantly increasing affinity and selectivity. We further tailored fluorophores to the binder, yielding “Sylite”—a probe with outstanding signal-to-background ratio that outperforms antibodies in tissue staining with rapid and efficient penetration, mitigation of staining artifacts, and simplified handling. In super-resolution microscopy Sylite precisely localizes the inhibitory synapse and enables nanoscale measurements. Sylite profiles inhibitory inputs and synapse sizes of excitatory and inhibitory neurons in the midbrain and combined with complimentary tracing techniques reveals the synaptic connectivity.

Original languageAmerican English
Article numbere202202078
JournalAngewandte Chemie - International Edition
Volume61
Issue number30
DOIs
StatePublished - 25 Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Keywords

  • Dimerization
  • Fluorescent Probes
  • Neuroscience
  • Peptides
  • Super-Resolution Microscopy

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