Modeling and simulation of neocortical micro- and mesocircuitry (Part II, Physiology and experimentation)

Cortical dynamics underlie many cognitive processes and emerge from complex multiscale interactions, which are challenging to study in vivo. Large-scale, biophysically detailed models offer a tool that can complement laboratory approaches. We present a model comprising eight somatosensory cortex subregions, 4.2 million morphological and electrically detailed neurons, and 13.2 billion local and mid-range synapses. In silico tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. The model reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, how cortical activity is shaped by high-dimensional connectivity motifs in local and mid-range connectivity, and spatial targeting rules by inhibitory subpopulations. The latter was facilitated using a rewired connectome that included specific targeting rules observed for different inhibitory neuron types in electron microscopy. The model also predicted the role of inhibitory interneuron types and different layers in stimulus encoding. Simulation tools and a large subvolume of the model are made available to enable further community-driven improvement, validation, and investigation.

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Publication Details

Journal
eLife
Published
2026-01-20
DOI
https://doi.org/10.7554/elife.99693.3
Primary Topic
Neural dynamics and brain function
Type
article
Field-Weighted Citation Impact
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article

Modeling and simulation of neocortical micro- and mesocircuitry (Part II, Physiology and experimentation)

Giuseppe Chindemi, Alexis Arnaudon, Maria Reva, Omar Awile et al.
eLife
Neural dynamics and brain function
article

Modeling and simulation of neocortical micro- and mesocircuitry (Part II, Physiology and experimentation)

Giuseppe Chindemi, Alexis Arnaudon, Maria Reva, Omar Awile, Daniela Egas Santander, András Ecker, Srikanth Ramaswamy, Genrich Ivaska, Samuel Lapere, Tanguy Damart, Darshan Mandge, James B. Isbister, Rajnish Ranjan, Vishal Sood, Gianluca Ficarelli, Sirio Bolaños‐Puchet, Felix Schuermann, Joni Herttuainen, Christoph Pokorny, Pramod Kumbhar, Thomas Delemontex, Polina Litvak, James King, Aleksandra Teska, Weina Ji, Fernando Pereira, Anil M. Tuncel, Mike Gevaert, Judit Santilari Planas, Armando Romani, Daniel Keller, Henry Markram, Christian Rössert, Eilif B Muller, Elvis Boci, Matthias Wolf, Barros-Zulaica Natali, Jean-Denis Courcol, Jorge Blanco Alonso, Alexander Dietz, Wener Van Geit, Michael W Reimann
article en

Abstract

Cortical dynamics underlie many cognitive processes and emerge from complex multiscale interactions, which are challenging to study in vivo. Large-scale, biophysically detailed models offer a tool that can complement laboratory approaches. We present a model comprising eight somatosensory cortex subregions, 4.2 million morphological and electrically detailed neurons, and 13.2 billion local and mid-range synapses. In silico tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. The model reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, how cortical activity is shaped by high-dimensional connectivity motifs in local and mid-range connectivity, and spatial targeting rules by inhibitory subpopulations. The latter was facilitated using a rewired connectome that included specific targeting rules observed for different inhibitory neuron types in electron microscopy. The model also predicted the role of inhibitory interneuron types and different layers in stimulus encoding. Simulation tools and a large subvolume of the model are made available to enable further community-driven improvement, validation, and investigation.

eLifeVol. 13
University of Geneva (CH), Centre Hospitalier Universitaire Sainte-Justine (CA), École Polytechnique Fédérale de Lausanne (CH), Université de Montréal (CA), Newcastle University (GB)
Openalex Percentile: Top 84%
Neural dynamics and brain function
DOIOpen Access PDFOpenAlex
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