Light-sheet microscopy or Ultramicroscopy, stands out for its efficient and gentle 3D imaging of large samples, such as an entire mouse, compared to conventional epifluorescent microscopy techniques like widefield or confocal. In light-sheet microscopy, a transparent specimen is illuminated from the side with a thin light sheet. This technique allows for quick optical sectioning and minimal out-of-focus illumination. Photobleaching is reduced, and imaging speed is increased due to the exclusion of out-of-focus light through a pinhole. Modified from Dodt et al. 2007. Dodt et al. 2007. Selected literature Dodt, H.-U. et al. Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain. Nat. Methods 4, 331–336 (2007).Siedentopf, H. & Zsigmondy, R. U ̈ ber Sichtbarmachung und Gro ̈enbestimmung ultramikroskopischer Teilchen, mit besonderer Anwendung auf Goldrubingla ̈ser. Annalen der Physik 10, 1–39 (1903).Keller, P.J. & Dodt, H.U. Light sheet microscopy of living or cleared specimens. Curr. Opin. Neurobiol. 22, 138–143 (2012).Ueda, H. R. et al. Whole-Brain Profiling of Cells and Circuits in Mammals by Tissue Clearing and Light-Sheet Microscopy. Neuron 106, 369–387 (2020).Becker, K., Jährling, N., Kramer, E.R., Schnorrer, F. & Dodt, H.U. Ultramicroscopy: 3D reconstruction of large microscopical specimens. J. Biophotonics 1, 36–42 (2008). This article was published on 2024-09-09