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Multiscale model of primary motor cortex circuits reproduces in vivo cell type-specific dynamics associated with behavior

View ORCID ProfileSalvador Dura-Bernal, Samuel A Neymotin, Benjamin A Suter, Joshua Dacre, Julia Schiemann, Ian Duguid, Gordon MG Shepherd, William W Lytton
doi: https://doi.org/10.1101/2022.02.03.479040
Salvador Dura-Bernal
1Department. of Physiology and Pharmacology, State University of New York Downstate Health Sciences University, United States
2Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, United States
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  • ORCID record for Salvador Dura-Bernal
  • For correspondence: salvadord.dura-bernal@downstate.edu
Samuel A Neymotin
2Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, United States
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Benjamin A Suter
3Department of Physiology, Northwestern University, United States
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Joshua Dacre
4Centre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, United Kingdom
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Julia Schiemann
4Centre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, United Kingdom
5Center for Integrative Physiology and Molecular Medicine, Saarland University, Germany
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Ian Duguid
4Centre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, United Kingdom
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Gordon MG Shepherd
3Department of Physiology, Northwestern University, United States
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William W Lytton
1Department. of Physiology and Pharmacology, State University of New York Downstate Health Sciences University, United States
6Department of Neurology, Kings County Hospital Center, Brooklyn, USA
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Abstract

Understanding cortical function requires studying its multiple scales: molecular, cellular, circuit and behavior. We developed a biophysically detailed multiscale model of mouse primary motor cortex (M1) with over 10,000 neurons, 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity and dendritic synapse locations were derived from experimental data. The model includes long-range inputs from 7 thalamic and cortical regions, and noradrenergic inputs from locus coeruleus. Connectivity depended on cell class and cortical depth at sublaminar resolution. The model reproduced and predicted in vivo layer- and cell type-specific responses (firing rates and LFP) associated with behavioral states (quiet and movement) and experimental manipulations (noradrenaline receptor blocking and thalamus inactivation), and enabled us to evaluate different hypotheses of the circuitry and mechanisms involved. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the M1 cell type-specific multiscale dynamics associated with a range of experimental conditions and behaviors.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 06, 2022.
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Multiscale model of primary motor cortex circuits reproduces in vivo cell type-specific dynamics associated with behavior
Salvador Dura-Bernal, Samuel A Neymotin, Benjamin A Suter, Joshua Dacre, Julia Schiemann, Ian Duguid, Gordon MG Shepherd, William W Lytton
bioRxiv 2022.02.03.479040; doi: https://doi.org/10.1101/2022.02.03.479040
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Multiscale model of primary motor cortex circuits reproduces in vivo cell type-specific dynamics associated with behavior
Salvador Dura-Bernal, Samuel A Neymotin, Benjamin A Suter, Joshua Dacre, Julia Schiemann, Ian Duguid, Gordon MG Shepherd, William W Lytton
bioRxiv 2022.02.03.479040; doi: https://doi.org/10.1101/2022.02.03.479040

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