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

Salvador Dura-Bernal*, Samuel A. Neymotin, Benjamin A. Suter, Joshua Dacre, Joao V.S. Moreira, Eugenio Urdapilleta, Julia Schiemann, Ian Duguid, Gordon M.G. Shepherd, William W. Lytton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number112574
JournalCell reports
Volume42
Issue number6
DOIs
StatePublished - Jun 27 2023

Keywords

  • CP: Neuroscience
  • cell type-specific
  • computational model
  • cortical circuits
  • local field potentials
  • motor cortex
  • motor thalamus
  • multiscale
  • neural dynamics
  • neural manifolds
  • noradrenaline

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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