title: A platform for brain-wide imaging and reconstruction of individual neurons.
abstract: The structure of axonal arbors controls how signals from individual neurons are routed within the mammalian brain. However, the arbors of very few long-range projection neurons have been reconstructed in their entirety, as axons with diameters as small as 100 nm arborize in target regions dispersed over many millimeters of tissue. We introduce a platform for high-resolution, three-dimensional fluorescence imaging of complete tissue volumes that enables the visualization and reconstruction of long-range axonal arbors. This platform relies on a high-speed two-photon microscope integrated with a tissue vibratome and a suite of computational tools for large-scale image data. We demonstrate the power of this approach by reconstructing the axonal arbors of multiple neurons in the motor cortex across a single mouse brain.
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Economo
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Nathan G
authors.initials: NG
authors.lastname: Clack
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Lavis
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.|Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, United States.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Gerfen
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Karel
authors.initials: K
authors.lastname: Svoboda
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Eugene W
authors.initials: EW
authors.lastname: Myers
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Jayaram
authors.initials: J
authors.lastname: Chandrashekar
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D051379:Mice; D009474:Neurons / Q000166:cytology*; D061848:Optical Imaging / Q000379:methods*
keywords: Axonal reconstruction; Neuroanatomy; Neuroinformatics; Tissue clearing; Whole-brain imaging; mouse; neuroscience