A novel method called Light-microscopy-based Connectomics (LICONN) allows researchers to map the brain’s complex neural networks at a nanoscale. LICONN will enable synapse-level phenotyping of brain tissue in biological experiments in a readily adoptable manner.
Over the years, researchers studying brain connectivity have encountered a challenging trade-off: They can either see the detailed physical structure of neural connections using electron microscopy (EM) or identify specific molecules using light microscopy. However, it is not possible to do both simultaneously at the resolution needed to trace individual connections.
LICONN offers a solution to this limitation by combining conventional light microscopy with hydrogel expansion techniques and AI. The researchers behind this believe that this is the first tool beyond electron microscopy capable of reconstructing brain tissue with all synaptic connections between neurons.
The research group outlined their methods in a Nature publication titled: “Light-microscopy-based connectomic reconstruction of mammalian brain tissue.” They explained that the technology expands brain tissue samples around 16-fold while maintaining structural integrity. Next, machine learning analyses the expanded samples and reconstructs their detailed cellular structure.
This method achieves an increase in resolution through hydrogel expansion instead of optical super-resolution. Thus, this innovation exploits the speed, optical sectioning, and availability of standard disk confocal microscopes.
The most significant advantage of LINCONN is that it makes high-resolution brain mapping accessible to more researchers. While electron microscopy requires specialised equipment and expertise, LICONN can be integrated with standard lab microscopes.
The authors of this study said: “LICONN is highly accessible. Acquisition is driven by broadly available conventional light-microscopy hardware… although LICONN sample preparation introduces new strategies to achieve high-fidelity tissue expansion, the protocol is not fundamentally more complex than previous expansion techniques that have been widely adopted.”
As neurologists continue to reveal the complex wiring of the brain, technologies like LICONN that bridge the gap between physical connections and molecular function promise to accelerate our understanding of how the brain works.