Innovative Protein 'Barcodes' Revolutionize Large-Scale Brain Circuit Mapping

Researchers from E11 Bio, a nonprofit focused on advanced neuroscience tools, have unveiled a groundbreaking technology that significantly enhances the accuracy and cost-efficiency of mapping neural connections in the brain. This new approach utilizes unique protein 'barcodes' to label individual neurons, enabling precise reconstruction of their shapes from microscopy images.

Traditionally, creating detailed connectomic maps—comprehensive wiring diagrams of neural networks—has been prohibitively expensive and time-consuming, with costs reaching into billions of dollars for a single mouse brain. The main challenge lies in converting high-resolution microscopy images into digital neuron reconstructions, a process hampered by errors that require extensive manual correction.

E11 Bio’s innovation involves genetically engineering neurons to express hundreds of thousands of distinct protein barcode combinations. These barcodes serve as unique identifiers for each neuron, allowing artificial intelligence algorithms to reconstruct neuronal structures with nearly ten times more accuracy than existing methods. This approach, named PRISM, integrates these barcodes with multiplexed expansion microscopy and advanced machine learning for automated, scalable neuron tracing.

The team envisions expanding the barcode diversity to include millions or even billions, which could reduce the mapping costs by over 100 times. The barcode system also facilitates the localization of natural proteins within neurons, offering insights into synaptic structures and signaling pathways. In their recent preprint, the researchers demonstrated the ability to identify five pre- and post-synaptic proteins and uncovered new organizational principles in complex synaptic formations.

This technological advancement holds the potential to transform neuroscience, similar to how the Human Genome Project revolutionized genetics. By enabling detailed mapping of mammalian brain circuits at a fraction of current costs, it could accelerate understanding of brain function, aid in diagnosing and treating neurological disorders, and inspire innovations in artificial intelligence and neural network design.

More information can be found in the bioRxiv preprint: DOI: 10.1101/2025.09.26.678648.

Source: https://medicalxpress.com/news/2025-10-protein-barcodes-brain-circuits-scale.html