title: Saturated Reconstruction of a Volume of Neocortex.
abstract: We describe automated technologies to probe the structure of neural tissue at nanometer resolution and use them to generate a saturated reconstruction of a sub-volume of mouse neocortex in which all cellular objects (axons, dendrites, and glia) and many sub-cellular components (synapses, synaptic vesicles, spines, spine apparati, postsynaptic densities, and mitochondria) are rendered and itemized in a database. We explore these data to study physical properties of brain tissue. For example, by tracing the trajectories of all excitatory axons and noting their juxtapositions, both synaptic and non-synaptic, with every dendritic spine we refute the idea that physical proximity is sufficient to predict synaptic connectivity (the so-called Peters' rule). This online minable database provides general access to the intrinsic complexity of the neocortex and enables further data-driven inquiries.
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: bobby.kasthuri@gmail.com.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Kasthuri
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Kenneth Jeffrey
authors.initials: KJ
authors.lastname: Hayworth
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Daniel Raimund
authors.initials: DR
authors.lastname: Berger
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Richard Lee
authors.initials: RL
authors.lastname: Schalek
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: José Angel
authors.initials: JA
authors.lastname: Conchello
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Seymour
authors.initials: S
authors.lastname: Knowles-Barley
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Dongil
authors.initials: D
authors.lastname: Lee
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Amelio
authors.initials: A
authors.lastname: Vázquez-Reina
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Verena
authors.initials: V
authors.lastname: Kaynig
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Thouis Raymond
authors.initials: TR
authors.lastname: Jones
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Roberts
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Josh Lyskowski
authors.initials: JL
authors.lastname: Morgan
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Tapia
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: H Sebastian
authors.initials: HS
authors.lastname: Seung
authors.affiliation: Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218-2128, USA.
authors.forename: William Gray
authors.initials: WG
authors.lastname: Roncal
authors.affiliation: Department of Statistical Science and Neurobiology, Duke University, Durham, NC 27708, USA.
authors.forename: Joshua Tzvi
authors.initials: JT
authors.lastname: Vogelstein
authors.affiliation: Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218-2128, USA.
authors.forename: Randal
authors.initials: R
authors.lastname: Burns
authors.affiliation: Department of Statistics, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Daniel Lewis
authors.initials: DL
authors.lastname: Sussman
authors.affiliation: Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218-2682, USA.
authors.forename: Carey Eldin
authors.initials: CE
authors.lastname: Priebe
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Pfister
authors.affiliation: Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: jeff@mcb.harvard.edu.
authors.forename: Jeff William
authors.initials: JW
authors.lastname: Lichtman
mesh_terms: D000818:Animals; D001331:Automation; D001369:Axons / Q000648:ultrastructure; D003712:Dendrites / Q000648:ultrastructure; D051379:Mice; D008855:Microscopy, Electron, Scanning / Q000379:methods*; D008867:Microtomy / Q000379:methods*; D019579:Neocortex / Q000166:cytology / Q000648:ultrastructure*; D009474:Neurons / Q000648:ultrastructure*; D013569:Synapses / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000648:ultrastructure