Genetically encoded, nature-inspired transparency in the mammalian brain

Imagine if we could watch the brain in action – deep inside – without surgery or implants. That bold vision drives our Big Ideas in Neuroscience project. Inspired by animals like glass frogs, whose organs are naturally see-through, we are developing a new kind of laboratory mouse with a transparent brain. This transformative approach combines cutting-edge physics and biology to eliminate the intrinsic opacity of brain tissue in live mammals. In most mammals, such as rodents and humans, the brain scatters light, making it difficult to see what lies beneath the surface. In contrast, glass frogs produce special proteins that match the optical properties of their tissues, allowing light to pass through with minimal distortion. We aim to replicate this level of transparency in the mammalian brain by introducing proteins with similar optical properties using safe genetic techniques. The ability to achieve transparency in the brain holds significance for neuroscience, as many of the brain’s important control centers – including those for hunger, thirst, stress, emotion, memory, and social behavior – are buried deep beneath the surface. Our approach would enable scientists to observe and influence these circuits in real time, in awake, behaving animals, without the need for invasive procedures. This research has the potential to fundamentally change how we study the brain and treat neurological diseases. It paves the way for safer, more precise therapies and a deeper understanding of how the brain drives behavior. Much like the discovery of fluorescent proteins revolutionized biology, transparent brains could transform the future of neuroscience.