Zhao, Y.-J. et al. Light: Science & Application 7, 17153 (2018).

Imaging neuronal structure or activity in vivo requires invasive window preparations because of the skull's opacity, but such approaches are technically demanding and associated with inflammation. Zhao et al. present an alternative method for obtaining a clear view of the mouse brain. The researchers found that application of either collagenase or the chelator EDTA (depending on the animal's age) followed by glycerol renders the mouse skull optically transparent. In mice up to one month old, the researchers could image neuronal morphology (including spines), microglia, vasculature and calcium activity through the cleared skull. For older animals, the technology could be combined with thinning of the skull for similar results. The method does not result in noticeable inflammation and can be repeated for longitudinal imaging studies.