A universal workflow for creation, validation, and generalization of detailed neuronal models.

Detailed single-neuron modeling is widely used to study neuronal functions. While cellular and functional diversity across the mammalian cortex is vast, most of the available computational tools focus on a limited set of specific features characteristic of a single neuron. Here, we present a generalized automated workflow for the creation of robust electrical models and illustrate its performance by building cell models for the rat somatosensory cortex. Each model is based on a 3D morphological reconstruction and a set of ionic mechanisms. We use an evolutionary algorithm to optimize neuronal parameters to match the electrophysiological features extracted from experimental data. Then we validate the optimized models against additional stimuli and assess their generalizability on a population of similar morphologies. Compared to the state-of-the-art canonical models, our models show 5-fold improved generalizability. This versatile approach can be used to build robust models of any neuronal type.

A calcium-based plasticity model for predicting long-term potentiation and depression in the neocortex.

Pyramidal cells (PCs) form the backbone of the layered structure of the neocortex, and plasticity of their synapses is thought to underlie learning in the brain. However, such long-term synaptic changes have been experimentally characterized between only a few types of PCs, posing a significant barrier for studying neocortical learning mechanisms. Here we introduce a model of synaptic plasticity based on data-constrained postsynaptic calcium dynamics, and show in a neocortical microcircuit model that a single parameter set is sufficient to unify the available experimental findings on long-term potentiation (LTP) and long-term depression (LTD) of PC connections. In particular, we find that the diverse plasticity outcomes across the different PC types can be explained by cell-type-specific synaptic physiology, cell morphology and innervation patterns, without requiring type-specific plasticity. Generalizing the model to in vivo extracellular calcium concentrations, we predict qualitatively different plasticity dynamics from those observed in vitro. This work provides a first comprehensive null model for LTP/LTD between neocortical PC types in vivo, and an open framework for further developing models of cortical synaptic plasticity.