Multiscale model of primary motor cortex circuits predicts in vivo dynamics (Dura-Bernal et al 2023)


Understanding cortical function requires studying multiple scales: molecular, cellular, circuit and behavior. We developed 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 were 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 predicted 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 generated 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. Publication: Dura-Bernal S, Neymotin SA, Suter BA, Dacre J, Moreira JVS, Urdapilleta E, Schiemann J, Duguid I, Shepherd GMG, Lytton WW. "Multiscale model of primary motor cortex circuits predicts in vivo cell type-specific, behavioral state-dependent dynamics." Cell Reports (In Press)

Model Type: Realistic Network; Spiking neural network

Region(s) or Organism(s): Neocortex; Mouse

Cell Type(s): Neocortex L2/3 pyramidal GLU cell; Neocortex M1 interneuron basket PV GABA cell; Neocortex M1 interneuron chandelier SOM GABA cell; Neocortex M1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex M1 L5B pyramidal pyramidal tract GLU cell; Neocortex M1 L6 pyramidal corticothalamic GLU cell; Neocortex L5/6 pyramidal GLU cell; Hodgkin-Huxley neuron; Neocortex primary motor area pyramidal layer 5 corticospinal cell; Neocortex layer 2-3 interneuron; Neocortex layer 5 interneuron

Currents: I Sodium; I Potassium; I Calcium; TASK channel

Receptors: GabaA; GabaB; NMDA; AMPA

Transmitters: Gaba; Glutamate; Norephinephrine

Model Concept(s): Multiscale; Motor control; Posture and locomotion; Oscillations

Simulation Environment: NEURON; NetPyNE

Implementer(s): Dura-Bernal, Salvador [salvadordura at gmail.com]

References:

Dura-Bernal S et al. (). Multiscale model of primary motor cortex circuits predicts in vivo cell type-specific, behavioral state-dependent dynamics Cell Rep..


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