Skull optical clearing window for in vivo imaging of the mouse cortex at synaptic resolution

A non-invasive approach for creating an optical window in the skull to enable the brains of living mice to be imaged has been demonstrated. Dan Zhu and co-workers from Huazhong University of Science and Technology, China, tested the use of optical clearing agents that they applied to the bare skulls (hair and skin removed) of living mice. The agents, which include collagenase, EDTA disodium and glycerol, were used to soften the skull and reduce optical scattering by refractive index matching. A water-immersion lens was then used to perform in vivo, two-photon imaging of neurons, microglia and the microvasculature in the mouse brain. The easy handling and safety of this method make it promising for use in neuroscience research.