Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics.

Autor:	Dura-Bernal S; Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, USA; Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA. Electronic address: salvador.dura-bernal@downstate.edu., Neymotin SA; Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA; Department of Psychiatry, Grossman School of Medicine, New York University (NYU), New York, NY, USA., Suter BA; Department of Physiology, Northwestern University, Evanston, IL, USA., Dacre J; Centre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh, UK., Moreira JVS; Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, USA., Urdapilleta E; Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, USA., Schiemann J; Centre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh, UK; Center for Integrative Physiology and Molecular Medicine, Saarland University, Saarbrücken, Germany., Duguid I; Centre for Discovery Brain Sciences, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh, UK., Shepherd GMG; Department of Physiology, Northwestern University, Evanston, IL, USA., Lytton WW; Department of Physiology and Pharmacology, State University of New York (SUNY) Downstate Health Sciences University, Brooklyn, NY, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA; Department of Neurology, Kings County Hospital Center, Brooklyn, NY, USA.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Jun 27; Vol. 42 (6), pp. 112574. Date of Electronic Publication: 2023 Jun 09.
DOI:	10.1016/j.celrep.2023.112574
Abstrakt:	Understanding cortical function requires studying multiple scales: molecular, cellular, circuit, and behavioral. We develop a multiscale, biophysically detailed model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity, and dendritic synapse locations are constrained by experimental data. The model includes long-range inputs from seven thalamic and cortical regions and noradrenergic inputs. Connectivity depends on cell class and cortical depth at sublaminar resolution. The model accurately predicts in vivo layer- and cell-type-specific responses (firing rates and LFP) associated with behavioral states (quiet wakefulness and movement) and experimental manipulations (noradrenaline receptor blockade and thalamus inactivation). We generate mechanistic hypotheses underlying the observed activity and analyzed low-dimensional population latent dynamics. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the cell-type-specific multiscale dynamics associated with several experimental conditions and behaviors. Competing Interests: Declaration of interests The authors declare no competing interests. (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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