Broken or disrupted circuits in the brain contribute to many neurological disorders. A new custom-built biological "wire" developed at Duke University School of Medicine points the way toward a new treatment approach — bypassing broken brain connections, rather than relying on long-term medication or external stimulation.
Researchers led by Kafui Dzirasa, MD, PhD , developed a technology called LinCx that allows scientists to create new electrical connections between carefully chosen neurons. Unlike existing tools that often influence many cells at once, this approach enables selective, long‑lasting changes in how defined brain circuits function. The study is published in Nature on May 13, 2026.
"By introducing a way to plug in new electrical connections with cellular‑level precision, our study marks a major step forward in the ability to edit brain circuitry and understand how neural networks give rise to behavior," said Dzirasa, the A. Eugene and Marie Washington Presidential Distinguished Professor of Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences.
Rather than repairing faulty synapses, the technique installs a new electrical "bypass" between specific neurons, strengthening communication without directly modifying existing connections.
The technology is based on proteins originally found in fish that naturally form electrical synapses. Using protein engineering, the researchers redesigned these molecules so they dock only with a matching engineered partner and not with native brain proteins. Laboratory screening, including a newly developed fluorescence‑based assay, identified pairs with high specificity that reliably passed electrical signals between cells.
In mice, targeted electrical connections strengthened communication within specific circuits, reshaped brain‑wide activity patterns, and produced measurable changes in behavior, including social interaction and stress responses.
The team demonstrated the system's versatility in both worms and mice. In worms, adding new connections altered temperature‑seeking behavior. In mice, targeted electrical connections strengthened communication within specific circuits, reshaped brain‑wide activity patterns, and produced measurable changes in behavior, including social interaction and stress responses.
"For decades, neuroscience has lacked tools that can precisely control communication between specific cell types," Dzirasa said. Drugs, electrical stimulation, and optogenetics typically affect broad populations of cells, while prior attempts to use electrical synapses often resulted in unintended connections. LinCx overcomes these limitations and may be able to improve on these tools without requiring external stimulation.
"We will next test whether LinCx is powerful enough to override synaptic deficits induced by lifelong genetic disruptions," he said.
Other Duke authors: Elizabeth Ransey, Gwenaëlle E. Thomas, Ryan Bowman, Elise Adamson, Kathryn K. Walder-Christensen, Hannah Schwennesen, Caly Ferguson, Stephen D. Mague, Nenad Bursac.
Funding: The Burroughs Wellcome Fund, the Ernest E. Just Life Science Institute, the Hartwell Foundation, Hope for Depression Research Foundation, Howard Hughes Medical Institute, and the National Institutes of Health.
