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Updated: Apr 21, 2026
Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Streamlined correlative live-confocal and SBF-SEM imaging reveals early inflammatory dendritic changes induced by
Christoph Jähnig1, Nikola Tomov1, Adolfo Odriozola1
1Institute of Anatomy, University of Bern, Baltzerstrasse 2, Bern 3012, Switzerland.
Background:
As cells that constantly survey their environment, microglia rely on contact with neurons, non-neuronal cells and extracellular substances. The diversity of microglial receptors allows them to elicit either localized or widespread responses to developmental cues, functional states, tissue damage, or pathogens. These responses primarily affect microglia immediate vicinity. In neuroinflammation, aberrantly activated microglia are considered to damage adjacent neurons and impair their function. Understanding the dynamic relationship between microglia and neurons is essential for elucidating the full spectrum of functional and transcriptional microglial states.
New Methods:
This study presents a straightforward yet effective workflow correlative live-cell confocal microscopy and serial block-face scanning electron microscopy (SBF-SEM) to visualize microglia-neuron contacts in cell culture. This approach enables the identification and three-dimensional high-resolution imaging of sites of intense cellular interaction.
Results:
We visualized initial membrane contact zones and early organelle alterations at of microglia-neuron interfaces. Our data showed that stimulation with Gram-positive bacterial lysates (from Streptococcus pneumoniae) or Gram-negative lipopolysaccharide (from Escherichia coli) induced distinct patterns of microglial activation. These were characterized by increased adherence to neurites and reduced motility. Notably, local mitochondrial swelling and dendrite shrinkage, were observed shortly after microglial attachment.
Comparison With Existing Methods:
Our workflow substantially improves the resolution to study microglia-neuron interactions at and enables detection of changes unvisualizable by light microscopy.
Conclusion:
The proposed method provides a powerful platform for investigating functional states of microglia and their interactions with surrounding cells, and it is readily adaptable to research context beyond neuroinflammation.
Insights
Microglia interact closely with neurons, and this study reveals how bacterial stimulation alters these contacts, causing neuronal damage. Our new imaging method visualizes these crucial microglia-neuron interactions in detail.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia are immune cells in the brain that constantly monitor their environment.
- Their interactions with neurons are crucial for brain function and can be altered in neuroinflammation.
- Understanding these dynamic relationships is key to understanding microglial states.
Purpose of the Study:
- To develop and apply a novel workflow for visualizing microglia-neuron contacts.
- To investigate the impact of bacterial stimuli on microglia-neuron interactions at high resolution.
Main Methods:
- Correlative live-cell confocal microscopy and serial block-face scanning electron microscopy (SBF-SEM).
- This workflow enables high-resolution, 3D imaging of cellular interactions.
- Allows visualization of changes previously undetectable by light microscopy.
Main Results:
- Visualized initial membrane contact zones and organelle changes at microglia-neuron interfaces.
- Bacterial lysate and LPS stimulation induced distinct microglial activation patterns, including increased adherence to neurites and reduced motility.
- Observed local mitochondrial swelling and dendrite shrinkage following microglial attachment.
Conclusions:
- The developed workflow provides a powerful platform for studying microglia-neuron interactions.
- This method enhances the investigation of microglial functional states.
- The technique is adaptable for research beyond neuroinflammation.
