PT  - JOURNAL ARTICLE
AU  - Beatriz Herrera
AU  - Amirsaman Sajad
AU  - Geoffrey F. Woodman
AU  - Jeffrey D. Schall
AU  - Jorge J. Riera
TI  - A Minimal Biophysical Model of Neocortical Pyramidal Cells: Implications for Frontal Cortex Microcircuitry and Field Potential Generation
AID  - 10.1101/2020.01.29.925180
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.29.925180
4099  - http://biorxiv.org/content/early/2020/01/30/2020.01.29.925180.short
4100  - http://biorxiv.org/content/early/2020/01/30/2020.01.29.925180.full
AB  - Ca2+ spikes initiated in the apical dendrites of layer-5 pyramidal cells (PC) underlie nonlinear dynamic changes in the gain of cellular response, which is critical for top-down cognitive control. Detailed models with several compartments and dozens of ionic channels have been proposed to account for this Ca2+ spike-dependent gain with its associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We present a minimal 2-compartment biophysical model, overcoming these limitations. In our model, a basal-dendritic/somatic compartment included typical Na+ and K+ conductances, while an apical-dendritic/trunk compartment included persistent Na+, hyperpolarization-activated cation (Ih), slow inactivation K+, muscarinic K+, and Ca2+ L-type. The model replicated the Ca2+ spike morphology and its critical frequency plus three other defining features of layer-5 PC synaptic integration: linear frequency-current relationships, backpropagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking Ih. Simulating 1,000 synchronized layer-5 PCs, we reproduced the current source density patterns evoked by Ca2+-spikes both with and without Ih current. Thus, a 2-compartment model with five non-classic ionic currents in the apical-dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials such as the error-related negativity.Significance Statement A tractable model of layer-5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. This minimal model enables new multi-scale investigations of microcircuit functions with associated current flows measured by intracranial local field potentials. It thus establishes a foundation for the future computational evaluation of scalp electroencephalogram signatures imprinted by Ca2+ spikes in pyramidal cells, a phenomenon underlying many brain cognitive processes.