How see-through brains could transform neuroscience

We talk with Wu Tsai Neuro Faculty Scholar Guosong Hong about how insights from glass frogs and our own eyes could help engineer transparent brains
Nicholas Weiler
From Our Neurons to Yours Wu Tsai Neuro Podcast

What if we could make the brain see-through? 

It sounds like science fiction, but it could revolutionize how we study the brain. So many techniques in neuroscience today depend on getting light in and out of the brain. Scientists use high-powered microscopes to watch brain cells light up as they fire. They use lasers to turn specific neurons on or off, mapping how different regions connect and communicate. 

But there's a fundamental problem: light doesn't penetrate very deep into biological tissue—typically less than a millimeter in the brain. It scatters, bends, and gets absorbed. That's just physics... or is it?

Actually, we know some tissues are already transparent, like the belly of a glass frog or the jelly within our eyes. And as wild as it sounds, scientists are now learning how to make the brain transparent too.

Today on the show, we're talking with Guosong Hong, a faculty scholar here at the Wu Tsai Neurosciences Institute and assistant professor of materials science and engineering at Stanford Engineering. 

Guosong has a unique reputation for developing creative techniques that literally shed light on the brain—from using fluorescent nanomaterials and focused ultrasound to create a virtual flashlight inside the skull, to discovering a common food dye that temporarily makes skin, muscle, and even parts of the brain transparent. He has recently won numerous awards for his work, including the MIND Prize, Sloan Research Fellowship, and a Vilcek Prize for Creative Promise in Biomedical Science.

Now, Guosong is teaming up with Stanford biologists Lauren O'Connell and Xiaoke Chen to take this work to the next level through a Wu Tsai Neuro Big Ideas grant, genetically engineering mice to have see-through brains from birth. 

We discuss the physics of transparency, the creative chemistry behind these breakthrough techniques, and how transparent brains could transform our understanding of how neural circuits work.
 

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Guosong Hong
Wu Tsai Neuro Faculty Scholar Guosong Hong is an assistant professor in the department of materials science and engineering at the Stanford Engineering.

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Glossary

Optical Transparency The property of a material that allows light to pass through it without significant scattering or absorption, making objects visible through it.

Scattering The phenomenon where light bounces off particles or structures in tissue, changing direction rather than traveling straight through. This is the main reason biological tissues aren't naturally transparent.

Refractive Index A measure of how much light bends when passing through a material. Mismatches in refractive index between different components of tissue cause light scattering.

Lipids Fatty molecules that make up cell membranes and are a major source of light scattering in biological tissues due to their different refractive index compared to water.

Optogenetics A neuroscience technique that uses light to control the activity of specific neurons that have been genetically modified to respond to light.

Fluorescence The emission of light by a substance (like certain proteins in neurons) that has absorbed light of a different wavelength. This is used to visualize active neurons under a microscope.

Two-Photon Microscopy An advanced imaging technique that uses focused laser light to see deeper into tissue than conventional microscopy, but still limited to about 1 millimeter in the brain.

Clearing Methods Chemical techniques that remove lipids or match refractive indices in tissue to make it transparent, but typically require fixing (killing) the tissue first.

Tartrazine A common yellow food dye (also known as FD&C Yellow 5) that Guosong's lab discovered can temporarily make living tissue transparent by absorbing scattered light.

Nanomaterials Extremely small particles (on the scale of billionths of a meter) that can be engineered to have special properties, like emitting light when stimulated by ultrasound.

Focused Ultrasound Sound waves at frequencies beyond human hearing that can be focused to a specific point deep in tissue, used in Guosong's work to activate light-emitting nanoparticles inside the brain.

Neural Circuits Networks of interconnected neurons that work together to process information and generate behavior.

Big Ideas in Neuroscience Wu Tsai Neurosciences Institute's flagship program that funds ambitious, collaborative research projects aimed at transforming our understanding of the brain.

Episode credits

This episode was produced by Michael Osborne at 14th Street Studios, with sound design by Mark Bell . Social media strategy is by Julia Diaz, and additional editing by Nathan Collins. Our logo is by Aimee Garza. The show is hosted by Nicholas Weiler at Stanford's Wu Tsai Neurosciences Institute and supported in part by the Knight Initiative for Brain Resilience. 

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Episode Transcript

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