Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy

Michael W Reimann; Sirio Bolaños-Puchet; Jean-Denis Courcol; Daniela Egas Santander; Alexis Arnaudon; Benoît Coste; Fabien Delalondre; Thomas Delemontex; Adrien Devresse; Hugo Dictus; Alexander Dietz; András Ecker; Cyrille Favreau; Gianluca Ficarelli; Mike Gevaert; Joni Herttuainen; James B Isbister; Lida Kanari; Daniel Keller; James King; Pramod Kumbhar; Samuel Lapere; Jᾱnis Lazovskis; Huanxiang Lu; Nicolas Ninin; Fernando Pereira; Judit Planas; Christoph Pokorny; Juan Luis Riquelme; Armando Romani; Ying Shi; Jason Smith; Vishal Sood; Mohit Srivastava; Werner Van Geit; Liesbeth Vanherpe; Matthias Wolf; Ran Levi; Kathryn Hess; Felix Schürmann; Eilif B Muller; Henry Markram; Srikanth Ramaswamy

doi:10.7554/elife.99688.2

Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy

Michael W Reimann^* (Corresponding Author)
, Sirio Bolaños-Puchet
, Jean-Denis Courcol
, Daniela Egas Santander
, Alexis Arnaudon
, Benoît Coste
, Fabien Delalondre
, Thomas Delemontex
, Adrien Devresse
, Hugo Dictus
, Alexander Dietz
, András Ecker
, Cyrille Favreau
, Gianluca Ficarelli
, Mike Gevaert
, Joni Herttuainen
, James B Isbister
, Lida Kanari
, Daniel Keller
, James King

Pramod Kumbhar, Samuel Lapere, Jᾱnis Lazovskis, Huanxiang Lu, Nicolas Ninin, Fernando Pereira, Judit Planas, Christoph Pokorny, Juan Luis Riquelme, Armando Romani, Ying Shi, Jason Smith, Vishal Sood, Mohit Srivastava, Werner Van Geit, Liesbeth Vanherpe, Matthias Wolf, Ran Levi, Kathryn Hess, Felix Schürmann, Eilif B Muller, Henry Markram^* (Corresponding Author), Srikanth Ramaswamy^* (Corresponding Author)

^*Corresponding author for this work

Mathematical Science

Research output: Contribution to journal › Article › peer-review

Abstract

The function of the neocortex is fundamentally determined by its repeating microcircuit motif, but also by its rich, interregional connectivity. We present a data-driven computational model of the anatomy of non-barrel primary somatosensory cortex of juvenile rat, integrating whole-brain scale data while providing cellular and subcellular specificity. The model consists of 4.2 million morphologically detailed neurons, placed in a digital brain atlas. They are connected by 14.2 billion synapses, comprising local, mid-range and extrinsic connectivity. We delineated the limits of determining connectivity from neuron morphology and placement, finding that it reproduces targeting by Sst+ neurons, but requires additional specificity to reproduce targeting by PV+ and VIP+ interneurons. Globally, connectivity was characterized by local clusters tied together through hub neurons in layer 5, demonstrating how local and interegional connectivity are complicit, inseparable networks. The model is suitable for simulation-based studies, and a 211,712 neuron subvolume is made openly available to the community.

Original language	English
Article number	99688
Number of pages	95
Journal	eLife
Volume	13
DOIs	https://doi.org/10.7554/elife.99688.2
Publication status	Published - 26 Nov 2024

Bibliographical note

The authors would like to thank Giuseppe Chindemi, Javier DeFelipe and Rajnish Ranjan for help with the scientific development of the model; Tristan Carel, James Dynes, Stefan Eilemann, Bruno Magalhães, Juan Hernando Vieites and Arseny Povolotsky for contributions and support to the engineering challenges; the BBP Core Services team for responding to IT requests and services surrounding the research; Marwan Abdellah, Elvis Boci and Nadir Roman Guerrero for help with visualizations of the model; Zoltán Kisvárday for supervision of morphology reconstruction efforts; Eva Kenny, Silvia Scarabelli and Riccardo Sinsi for help with project management; and Karin Holm, Akiko Sato and Georges Khazen for support of manuscript development and helpful discussions.

Funding

This study was supported by funding to the Blue Brain Project, a research center of the École polytechnique fédérale de Lausanne (EPFL), from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology. RL, JPS and JL were supported by EPSRC under grant number EP/P025072/1. RL was supported by a collaboration grant from EPFL. S.R. is supported by a Marie Sklodowska-Curie Global Fellowship Agreement 842492; Newcastle University Academic Track (NUAcT) Fellowship; Fulbright Research Scholarship; Lister Institute Prize Fellowship; Academy of Medical Sciences Springboard Award; Research grant from the Air Force Office of Scientific Research (FA9550-23-1-0533); International Brain Research Organization (IBRO) Earlycareer Award; Theoretical Sciences Visiting Program (TSVP) at the Okinawa Institute of Science and Technology (OIST).

Funders	Funder number
Engineering & Physical Sciences Research Council (EPSRC)	EP/P025072/1
European Research Council	842492
Air Force Office of Scientific Research	FA9550-23-1-0533
École Polytechnique Fédérale de Lausanne
Newcastle University
Academy of Medical Sciences
Fulbright Commission
Lister Institute of Preventive Medicine
International Brain Research Organization
Okinawa Institute of Science and Technology

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Reimann, M. W., Bolaños-Puchet, S., Courcol, J.-D., Egas Santander, D., Arnaudon, A., Coste, B., Delalondre, F., Delemontex, T., Devresse, A., Dictus, H., Dietz, A., Ecker, A., Favreau, C., Ficarelli, G., Gevaert, M., Herttuainen, J., Isbister, J. B., Kanari, L., Keller, D., ... Ramaswamy, S. (2024). Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy. eLife, 13, Article 99688. https://doi.org/10.7554/elife.99688.2

Reimann, MW, Bolaños-Puchet, S, Courcol, J-D, Egas Santander, D, Arnaudon, A, Coste, B, Delalondre, F, Delemontex, T, Devresse, A, Dictus, H, Dietz, A, Ecker, A, Favreau, C, Ficarelli, G, Gevaert, M, Herttuainen, J, Isbister, JB, Kanari, L, Keller, D, King, J, Kumbhar, P, Lapere, S, Lazovskis, J, Lu, H, Ninin, N, Pereira, F, Planas, J, Pokorny, C, Riquelme, JL, Romani, A, Shi, Y, Smith, J, Sood, V, Srivastava, M, Van Geit, W, Vanherpe, L, Wolf, M, Levi, R, Hess, K, Schürmann, F, Muller, EB, Markram, H & Ramaswamy, S 2024, 'Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy', eLife, vol. 13, 99688. https://doi.org/10.7554/elife.99688.2

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title = "Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy",

abstract = "The function of the neocortex is fundamentally determined by its repeating microcircuit motif, but also by its rich, interregional connectivity. We present a data-driven computational model of the anatomy of non-barrel primary somatosensory cortex of juvenile rat, integrating whole-brain scale data while providing cellular and subcellular specificity. The model consists of 4.2 million morphologically detailed neurons, placed in a digital brain atlas. They are connected by 14.2 billion synapses, comprising local, mid-range and extrinsic connectivity. We delineated the limits of determining connectivity from neuron morphology and placement, finding that it reproduces targeting by Sst+ neurons, but requires additional specificity to reproduce targeting by PV+ and VIP+ interneurons. Globally, connectivity was characterized by local clusters tied together through hub neurons in layer 5, demonstrating how local and interegional connectivity are complicit, inseparable networks. The model is suitable for simulation-based studies, and a 211,712 neuron subvolume is made openly available to the community.",

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AU - Reimann, Michael W

AU - Bolaños-Puchet, Sirio

AU - Courcol, Jean-Denis

AU - Egas Santander, Daniela

AU - Arnaudon, Alexis

AU - Coste, Benoît

AU - Delalondre, Fabien

AU - Delemontex, Thomas

AU - Devresse, Adrien

AU - Dictus, Hugo

AU - Dietz, Alexander

AU - Ecker, András

AU - Favreau, Cyrille

AU - Ficarelli, Gianluca

AU - Gevaert, Mike

AU - Herttuainen, Joni

AU - Isbister, James B

AU - Kanari, Lida

AU - Keller, Daniel

AU - King, James

AU - Kumbhar, Pramod

AU - Lapere, Samuel

AU - Lazovskis, Jᾱnis

AU - Lu, Huanxiang

AU - Ninin, Nicolas

AU - Pereira, Fernando

AU - Planas, Judit

AU - Pokorny, Christoph

AU - Riquelme, Juan Luis

AU - Romani, Armando

AU - Shi, Ying

AU - Smith, Jason

AU - Sood, Vishal

AU - Srivastava, Mohit

AU - Van Geit, Werner

AU - Vanherpe, Liesbeth

AU - Wolf, Matthias

AU - Levi, Ran

AU - Hess, Kathryn

AU - Schürmann, Felix

AU - Muller, Eilif B

AU - Markram, Henry

AU - Ramaswamy, Srikanth

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JO - eLife

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M1 - 99688

ER -

Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy

Abstract

Bibliographical note

Funding

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