Saturated Reconstruction of a Volume of Neocortex

Cell. 2015 Jul 30;162(3):648-61. doi: 10.1016/j.cell.2015.06.054.

Authors

Narayanan Kasthuri¹, Kenneth Jeffrey Hayworth², Daniel Raimund Berger³, Richard Lee Schalek², José Angel Conchello², Seymour Knowles-Barley², Dongil Lee², Amelio Vázquez-Reina⁴, Verena Kaynig⁴, Thouis Raymond Jones⁵, Mike Roberts⁴, Josh Lyskowski Morgan², Juan Carlos Tapia², H Sebastian Seung⁶, William Gray Roncal⁷, Joshua Tzvi Vogelstein⁸, Randal Burns⁷, Daniel Lewis Sussman⁹, Carey Eldin Priebe¹⁰, Hanspeter Pfister⁴, Jeff William Lichtman¹¹

Affiliations

¹ Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: bobby.kasthuri@gmail.com.
² Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
³ 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.
⁴ School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
⁵ 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.
⁶ Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218-2128, USA.
⁸ Department of Statistical Science and Neurobiology, Duke University, Durham, NC 27708, USA.
⁹ Department of Statistics, Harvard University, Cambridge, MA 02138, USA.
¹⁰ Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218-2682, USA.
¹¹ Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: jeff@mcb.harvard.edu.

PMID: 26232230
DOI: 10.1016/j.cell.2015.06.054

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Automation
Axons / ultrastructure
Dendrites / ultrastructure
Mice
Microscopy, Electron, Scanning / methods*
Microtomy / methods*
Neocortex / cytology
Neocortex / ultrastructure*
Neurons / ultrastructure*
Synapses / ultrastructure
Synaptic Vesicles / ultrastructure

Abstract

Publication types

MeSH terms

Grants and funding