What is it about?
Neurons communicate through long-distance connections that must be precisely organized for the brain to function properly. In many neurodevelopmental and psychiatric disorders, this organization is disrupted, but it is difficult to understand why. In this study, we developed a “brain-on-chip” system that recreates key features of brain circuits in a controlled environment. Using this platform, we show that increasing the activity of cortical neurons alone is enough to disrupt the normal spatial organization of their connections. Instead of forming precise, targeted connections, hyperactive neurons extend too far and connect to inappropriate regions, creating abnormal overlap between pathways. Importantly, this rewiring does not change how individual neurons respond, but instead alters how groups of neurons are recruited at the network level. These findings suggest that changes in neuronal activity during development can directly reshape brain wiring, providing new insights into how circuit dysfunction may arise in neurological disorders.
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Why is it important?
Our findings shows how a brain-on-chip approach can bridge the gap between in vivo and in vitro neuroscience. By recreating the spatial organization and directional connectivity of brain circuits in a microfluidic chip, we preserved key features of brain architecture and function while gaining experimental access for mechanistic studies. This made it possible to directly demonstrate that neuronal activity alone can disrupt topographic organization, offering a powerful new framework to study brain wiring and its dysfunction in disease.
Perspectives
For me, this work highlights how powerful brain-on-chip systems can be for uncovering mechanisms that might remain hidden in more complex or less controlled models. By simplifying the system while preserving key architectural features, we were able to isolate a fundamental principle of how activity shapes brain wiring. It was also particularly enjoyable from an engineering perspective. We adapted a geometric concept originally proposed by Nikola Tesla in 1920 and translated it at the micrometer scale. It is a reminder that scientific innovation often builds on ideas from the past, reinterpreted with new tools and technologies. There is something quite satisfying (and amusing) about citing a 1920s reference in a 2026 neuroscience paper.
Maxim Cazorla
Aix-Marseille Universite
Read the Original
This page is a summary of: Biologically grounded on-chip model identifies selective topographic reorganization within hyperexcitable corticostriatal networks, Proceedings of the National Academy of Sciences, March 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2513459123.
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