A new window into the brain: laser powered electron microscopy accelerates connectome mapping
Dec 9, 2025
Mapping the brain’s wiring is one of neuroscience’s toughest challenges, limited by slow and costly imaging tools. A new PEEM-based method could speed up whole-brain mapping, deepen our understanding of brain function and disease, and make connectomics accessible to far more researchers.
A worldwide multidisciplinary team consisting of scientists from Diamond Light Source University of Chicago, University of Illinois, Leiden University and Okinawa Institute of Science and Technology have joined forces to tackle one of the grand challenges in neuroscience: understanding how billions of neurons connect to form the brain’s intricate networks. To do this, the team employed Photoemission Electron Microscopy (PEEM), a more that 50 years-old technique that’s been primarily used to study the magnetic, chemical and electronic properties of materials and according to the authors, could now transform brain mapping. The study, published in PNAS, introduces PEEM as a new tool for connectomics, the field that seeks to chart every connection between neurons. By adapting a surface-science microscope for neuroscience, the team demonstrated that they could image brain tissue at synaptic resolution, hundreds of times faster than conventional techniques.
- (A) PEEM combines the advantages of SEM and TEM for high-throughput volume electron microscopy (vEM). (B) High-resolution PEEM image of a UTBS. (Top Right) We can visualize multiple synapses (red square) as evidenced by the presence of postsynaptic densities (PSD) and presynaptic vesicle clouds. (Bottom Right) Line cut resolution measurement. Field of view: 4.27 μm. (C) Dependence of PEEM images on illumination wavelength. Field of view: 20 μm.
Why it matters
Understanding how billions of neurons connect and communicate is one of the biggest challenges in modern science. Current electron microscopy methods, while powerful, are slow and costly when scaled to entire mammalian brains. Mapping a cubic millimetre of brain tissue can take months or even years. The new approach enhances PEEM’s capabilities by employing a state-of-the-art continuous waver laser and offers a way to dramatically accelerate this process, potentially reducing costs and time while maintaining the ultra-high resolution needed to trace neural circuits.
Using ultra-thin sections of mouse brain tissue stained with osmium and mounted on gold-coated silicon wafers, the researchers achieved 20-nanometre resolution, sufficient to clearly resolve individual synapses, the junctions between neurons. By employing ultraviolet laser illumination, they reached gigavoxel-per-second imaging speeds, vastly surpassing traditional transmission and scanning electron microscopy (TEM and SEM). Crucially, Diamond’s advanced laser-PEEM facility, part of the I06 beamline, showed that these rapid imaging rates could be achieved without damaging delicate brain samples, pointing towards large-scale, high-throughput brain mapping.
What makes this breakthrough so exciting is that advanced laser-driven electron microscopy allows us to peer into the heart of modern neuroscience, capturing vast areas of brain tissue with extraordinary detail and doing so far faster than traditional electron microscopy. For the first time, we can realistically imagine mapping large portions of a mammalian brain on a timescale that genuinely supports real scientific discovery.
Gabriel Karras, laser beamline scientist at Diamond
By bridging the worlds of physics and biology, the laser-PEEM approach opens the door to fast, high-resolution imaging across many fields. In neuroscience, it could enable the rapid mapping of entire mouse brains, a task that would take decades with current technologies, within just a few years using multiple parallel instruments.
Such datasets could transform our understanding of how neural circuits underlie thought, memory, and disease, paving the way for advances in artificial intelligence and brain-inspired computing. Beyond the brain, the same high-throughput imaging principles could benefit pathology, materials science and nanotechnology, offering new ways to study tissues, catalysts, and interfaces at unprecedented speed and scale.
To find out more about the I06 beamline or discuss potential applications, please contact Principal Beamline Scientist Larissa Ishibe-Veiga: larissa.ishibe-veiga@diamond.ac.uk.
Related publication
Wildenberg, G., Boergens, K. M., Lambert, L., Li, R., Craig, A., Man, M. K. L., Moradi, A., Rieger, J., Duan, H., Dhesi, S. S., Karras, G., Maccherozzi, F., Dani, K., Tromp, R., van der Molen, S. J., King, S. B., & Kasthuri, N. (2025). Photoemission electron microscopy for connectomics. Proceedings of the National Academy of Sciences, 122(48), e2521349122.
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
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