A new window into the brain: visualising neural connections
To understand how the brain works, it is essential to map it out in detail. This appears to be possible with a microscopy technique in which Leiden physicists excel. This breakthrough could significantly advance the human quest to understand brain functions.
How does information flow through the brain? To understand this, researchers aim to map the brain—from small networks of cells to the entire nervous system. In doing so, they hope not only to gain insight into how our brains function, but also to understand possible abnormalities, such as when connections between cells become disrupted in disease.
The research group of Professor Sense Jan van der Molen uses a microscope that reveals how brain structure is organized, down to the level of a synapse—the tiny junction where one neuron communicates with another cell.
Introducing the PEEM microscope in brain research
A joint Chicago–Leiden project introduces Photoemission Electron Microscopy (PEEM) as a new tool for imaging brain tissue. PEEM uses the photoelectric effect to generate images of selected materials. The researchers applied the technique to ultrathin slices of a mouse brain.
The microscope produced high-resolution images faster and at lower cost than conventional imaging methods such as transmission electron microscopy (TEM) or scanning electron microscopy (SEM). Once a sequential series of thin slices has been photographed, a 3D model of that brain region can be reconstructed.
Tuesday Talk - Microscopy reinvented: peeking into living worlds
On the 9th of December 2025 professor Sense Jan van der Molen gives a Tuesday Talk at the Faculty of Science on his research.
Offering faster and cheaper 3D brain imaging
Brain research has long been hindered by imaging techniques that are slow, expensive, and technically demanding. In this proof-of-concept study, however, PEEM changes the playing field. Compared with traditional electron microscopy, it lowers both the cost and the technical barriers.
‘At the current image resolution—20 nanometres—we can already identify synapses, the sites where electrical or chemical signals pass from one neuron to another,’ Van der Molen explains. ‘Our new method opens the door to large-scale brain research in the near future. The challenge is to produce the best possible images as quickly as possible.’
Optimizing resolution and samples
Another encouraging result is that PEEM images can be further improved—both in resolution and contrast—by preparing samples in ways optimized for the PEEM technique. In the coming years, the team will continue its collaboration with the Chicago researchers. Leiden’s new postdoc, Simona Borrelli, will soon begin producing images with an upgraded PEEM microscope that delivers even sharper results.
A catalyst for multidisciplinary discoveries
Van der Molen’s lab has spent years developing advanced microscopy for cutting-edge fundamental research. ‘The potential of combining PEEM and related techniques with research in the physical, chemical, and biomedical sciences is enormous,’ says Van der Molen.
Proceedings of the National Academy of Sciences
Photoemission electron microscopy for connectomics
Auteurs: Gregg Wildenberg, Kevin M. Boergens, Amin Moradi, Rudolf Tromp, Sense Jan van der Molen, et al.
https://www.pnas.org/doi/10.1073/pnas.2521349122