During puerility and adolescence, our encephalon goes done a batch of changes. But studying those changes successful juvenile mice is challenging because scientists don't person a measurement to many times image nan aforesaid animal's neural pathways arsenic they grow.
Now, by simply rubbing a solution into a juvenile mouse's scalp, researchers astatine Stanford tin make nan tegument transparent to each visible light, allowing them to image nan processing connections successful a surviving mouse's brain. And because nan method is reversible and non-invasive, nan researchers tin return to nan aforesaid animal complete days and weeks. The work, published Aug. 26 in PNAS, creates caller opportunities for investigation connected nan processing encephalon that could amended our knowing of neurodevelopmental disorders and lead to caller interventions.
This opens a literal model to peek into nan brain's development. Not only tin we image nan structures of these neurons, but we tin besides image nan neural activity complete clip successful an animal model. In nan future, this attack could alteration america to look astatine really these circuits shape during nan improvement of an animal."
Guosong Hong, adjunct professor of materials subject and engineering and elder writer connected nan paper
Harnessing basal laws for caller discoveries
Normally, ray scatters erstwhile it hits skin. Light scattering occurs whenever ray waves brushwood interfaces betwixt materials pinch different optical properties. So, nether nan skin, it besides scatters arsenic it encounters lipids, proteins, and molecules wrong tissue. Like trying to spot done sunlit fog, ray scattering causes akin challenges erstwhile they effort to peek wrong aliases done tissues.
"From a physics perspective, we're fundamentally a container of h2o pinch biomaterials," said Mark Brongersma, nan Stephen Harris Professor and professor of materials subject and engineering and co-author connected nan paper. "And nan mismatch successful their optical properties is why we can't spot done nan tegument aliases scalp."
The cardinal to making tegument transparent is by making nan h2o and biomaterials much akin successful their optical properties. This tin beryllium accomplished by raising nan refractive scale of nan h2o – really overmuch it bends ray – to lucifer nan refractive scale of nan remainder of nan biomaterials successful nan body. The researchers recovered that by mixing a compound called ampyrone into h2o and rubbing it connected nan tegument of a mouse, they could raise nan refractive scale of nan h2o successful nan mouse's skin, turning it transparent. And because ampyrone almost exclusively absorbs ultraviolet light, nan wrong of nan rodent tin beryllium seen pinch nan full visible spectrum.
"The truth that specified basal optics laws tin beryllium applied and activity successful a biologic strategy is conscionable astonishing to me," Brongersma said. "It wasn't clear whether nan physics and nan chemistry and nan biology would each statement up to make this happen."
The activity builds connected nan team's groundbreaking discovery of a compound that turns tegument transparent to reddish light, allowing them to position a mouse's soul organs without making an incision. Now, because ampyrone permits nan full visible spectrum of light, nan squad tin spot nan colors of greenish and yellowish fluorescent proteins that are commonly utilized to people neural activity. Young mice person very bladed skulls, truthful this fluorescence tin beryllium seen until nan rodent is astir 4 weeks aged (the balanced of a quality teen aliases early adult). The researchers were capable to many times image nan neurons of sedated juvenile mice and spot really neural activity changed successful awake mice responding to a puff of aerial connected their whiskers.
Source:
Journal reference:
Keck, C. H. C., et al. (2025). Color-neutral and reversible insubstantial transparency enables longitudinal deep-tissue imaging successful unrecorded mice. Proceedings of nan National Academy of Sciences. doi.org/10.1073/pnas.2504264122