title: Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain.
abstract: Visualizing entire neuronal networks for analysis in the intact brain has been impossible up to now. Techniques like computer tomography or magnetic resonance imaging (MRI) do not yield cellular resolution, and mechanical slicing procedures are insufficient to achieve high-resolution reconstructions in three dimensions. Here we present an approach that allows imaging of whole fixed mouse brains. We modified 'ultramicroscopy' by combining it with a special procedure to clear tissue. We show that this new technique allows optical sectioning of fixed mouse brains with cellular resolution and can be used to detect single GFP-labeled neurons in excised mouse hippocampi. We obtained three-dimensional (3D) images of dendritic trees and spines of populations of CA1 neurons in isolated hippocampi. Also in fruit flies and in mouse embryos, we were able to visualize details of the anatomy by imaging autofluorescence. Our method is ideally suited for high-throughput phenotype screening of transgenic mice and thus will benefit the investigation of disease models.
authors: Max Planck Institute of Psychiatry, Kraepelinstr. 2, 80804 Munich, Germany. dodt@mpipsykl.mpg.de
authors: Hans-Ulrich
authors: HU
authors: Dodt
authors: Ulrich
authors: U
authors: Leischner
authors: Anja
authors: A
authors: Schierloh
authors: Nina
authors: N
authors: Jährling
authors: Christoph Peter
authors: CP
authors: Mauch
authors: Katrin
authors: K
authors: Deininger
authors: Jan Michael
authors: JM
authors: Deussing
authors: Matthias
authors: M
authors: Eder
authors: Walter
authors: W
authors: Zieglgänsberger
authors: Klaus
authors: K
authors: Becker
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000648:ultrastructure*; D004331:Drosophila melanogaster / Q000648:ultrastructure*; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000295:instrumentation / Q000379:methods*; D009474:Neurons / Q000648:ultrastructure*