Modeling a layer 4-to-layer 2/3 module of a single column in rat neocortex: Interweaving in vitro and in vivo experimental observations

We report a step in constructing an in silico model of a neocortical column, focusing on the synaptic connection between layer 4 (L4) spiny neurons and L2/3 pyramidal cells in rat barrel cortex. It is based first on a detailed morphological and functional characterization of synaptically connected pairs of L4–L2/3 neurons from in vitro recordings and second, on in vivo recordings of voltage responses of L2/3 pyramidal cells to current pulses and to whisker deflection. In vitro data and a detailed compartmental model of L2/3 pyramidal cells enabled us to extract their specific membrane resistivity (≈16,000 ohms·cm2) and capacitance (≈0.8 μF/cm2) and the spatial distribution of L4–L2/3 synaptic contacts. The average peak conductance per L4 synaptic contact is 0.26 nS for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and 0.2 nS for NMDA receptors. The in vivo voltage response for current steps was then used to calibrate the model for in vivo conditions in the Down state. Consequently, the effect of a single whisker deflection was modeled by converging, on average, 350 ± 20 L4 axons onto the modeled L2/3 pyramidal cell. Based on values of synaptic conductance, the spatial distribution of L4 synapses on L2/3 dendrites, and the average in vivo spiking probability of L4 spiny neurons, the model predicts that the feed-forward L4-L2/3 connection on its own does not fire the L2/3 neuron. With a broader distribution in the number of L4 neurons or with slight synchrony among them, the L2/3 model does spike with low probability.