Reconstruction of neocortex: Organelles, compartments, cells, circuits, and activity

Nicholas L Turner; Thomas Macrina; J Alexander Bae; Runzhe Yang; Alyssa M Wilson; Casey Schneider-Mizell; Kisuk Lee; Ran Lu; Jingpeng Wu; Agnes L Bodor; Adam A Bleckert; Derrick Brittain; Emmanouil Froudarakis; Sven Dorkenwald; Forrest Collman; Nico Kemnitz; Dodam Ih; William M Silversmith; Jonathan Zung; Aleksandar Zlateski; Ignacio Tartavull; Szi-Chieh Yu; Sergiy Popovych; Shang Mu; William Wong; Chris S Jordan; Manuel Castro; JoAnn Buchanan; Daniel J Bumbarger; Marc Takeno; Russel Torres; Gayathri Mahalingam; Leila Elabbady; Yang Li; Erick Cobos; Pengcheng Zhou; Shelby Suckow; Lynne Becker; Liam Paninski; Franck Polleux; Jacob Reimer; Andreas S Tolias; R Clay Reid; Nuno Maçarico da Costa; H Sebastian Seung

doi:10.1016/j.cell.2022.01.023

Reconstruction of neocortex: Organelles, compartments, cells, circuits, and activity

Cell. 2022 Mar 17;185(6):1082-1100.e24. doi: 10.1016/j.cell.2022.01.023. Epub 2022 Feb 24.

Authors

Nicholas L Turner¹, Thomas Macrina¹, J Alexander Bae², Runzhe Yang¹, Alyssa M Wilson³, Casey Schneider-Mizell⁴, Kisuk Lee⁵, Ran Lu³, Jingpeng Wu³, Agnes L Bodor⁴, Adam A Bleckert⁴, Derrick Brittain⁴, Emmanouil Froudarakis⁶, Sven Dorkenwald¹, Forrest Collman⁴, Nico Kemnitz³, Dodam Ih³, William M Silversmith³, Jonathan Zung¹, Aleksandar Zlateski⁷, Ignacio Tartavull³, Szi-Chieh Yu³, Sergiy Popovych¹, Shang Mu³, William Wong³, Chris S Jordan³, Manuel Castro³, JoAnn Buchanan⁴, Daniel J Bumbarger⁴, Marc Takeno⁴, Russel Torres⁴, Gayathri Mahalingam⁴, Leila Elabbady⁴, Yang Li⁴, Erick Cobos⁶, Pengcheng Zhou⁸, Shelby Suckow⁴, Lynne Becker⁴, Liam Paninski⁹, Franck Polleux¹⁰, Jacob Reimer⁶, Andreas S Tolias¹¹, R Clay Reid⁴, Nuno Maçarico da Costa⁴, H Sebastian Seung¹²

Affiliations

¹ Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Computer Science Department, Princeton University, Princeton, NJ 08544, USA.
² Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Electrical and Computer Engineering Department, Princeton University, Princeton, NJ 08544, USA.
³ Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA.
⁴ Allen Institute for Brain Science, Seattle, WA 98109, USA.
⁵ Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Brain & Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁶ Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Center for Neuroscience and Artificial Intelligence, Baylor College of Medicine, Houston, TX 77030, USA.
⁷ Electrical Engineering and Computer Science Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁸ Department of Statistics, Columbia University, New York, NY 10027, USA; Center for Theoretical Neuroscience, Columbia University, New York, NY 10027, USA; Grossman Center for the Statistics of Mind, Columbia University, New York, NY 10027, USA.
⁹ Department of Statistics, Columbia University, New York, NY 10027, USA; Center for Theoretical Neuroscience, Columbia University, New York, NY 10027, USA; Grossman Center for the Statistics of Mind, Columbia University, New York, NY 10027, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Neuroscience, Columbia University, New York, NY 10027, USA; Kavli Institute for Brain Science at Columbia University, New York, NY 10027, USA.
¹⁰ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Neuroscience, Columbia University, New York, NY 10027, USA; Kavli Institute for Brain Science at Columbia University, New York, NY 10027, USA.
¹¹ Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Center for Neuroscience and Artificial Intelligence, Baylor College of Medicine, Houston, TX 77030, USA; Department of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USA.
¹² Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Computer Science Department, Princeton University, Princeton, NJ 08544, USA. Electronic address: sseung@princeton.edu.

Abstract

We assembled a semi-automated reconstruction of L2/3 mouse primary visual cortex from ∼250 × 140 × 90 μm³ of electron microscopic images, including pyramidal and non-pyramidal neurons, astrocytes, microglia, oligodendrocytes and precursors, pericytes, vasculature, nuclei, mitochondria, and synapses. Visual responses of a subset of pyramidal cells are included. The data are publicly available, along with tools for programmatic and three-dimensional interactive access. Brief vignettes illustrate the breadth of potential applications relating structure to function in cortical circuits and neuronal cell biology. Mitochondria and synapse organization are characterized as a function of path length from the soma. Pyramidal connectivity motif frequencies are predicted accurately using a configuration model of random graphs. Pyramidal cells receiving more connections from nearby cells exhibit stronger and more reliable visual responses. Sample code shows data access and analysis.

Keywords: mouse, cortex, 3D reconstruction, electron microscopy, calcium imaging, pyramidal cell, mitochondria, synaptic connectivity, inhibitory cell, visual cortex.

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
Mice
Microscopy, Electron
Neocortex* / physiology
Organelles
Pyramidal Cells / physiology
Synapses / physiology

Abstract

Publication types

MeSH terms

Grants and funding