(2011). Briefly, neurons were KRX 0401 represented as a compartmental, conductance-based model using reconstructed morphologies from rat S1. The compartments were separated in four zones: axon initial segment (AIS), soma, basal dendrites, and apical dendrites (Figure 1). The

full axon was not simulated; only the AIS was simulated (Figure 1, bottom row). Synapses at the postsynaptic cells were activated after spike detection in AIS in the control case and prerecorded spike trains otherwise. A conduction delay based on axonal path distance to the soma (assuming spike conduction velocity was 300 μm/ms; Stuart et al., 1997) was accounted for. Passive membrane capacitance was 1 μF/cm2 for the soma, AIS, and dendrites, whereas for pyramids it was 2 μF/cm2 for basal and apical dendrites to correct for dendritic spine area. Axial resistance was 100 Ω cm for all compartments. Input resistance Rin was 225 ± 41 MΩ for L4 pyramids and 74 ± 35 MΩ for L5 pyramids. For basket cells, Rin = 379 ± 210 MΩ. The resting potential was −74.1 ± 0.1 mV for L4 pyramids, −73.8 ± 0.1 mV for L5 pyramids, and −71.6 ± 1.4 mV for basket cells. Up to ten active membrane conductance types were accounted for with kinetics taken from the published ion channel models or from published experimental

data (Hay et al., 2011). The reversal potentials for sodium and potassium were 50 and −85 mV, respectively, and −45 mV was used for the Ih current. Ion currents were modeled using the Hodgkin-Huxley formalism. Connectivity patterns were implemented as presented in Hill et al. (2012). Briefly, reconstructed cells from L4 and L5 were placed in a hexagonal volume with a radius of 320 μm, matching biological PD0332991 solubility dmso densities

of approx. 240,000 per mm3 in L4 and 90,000 per mm3 in L5 (J. Gonzalez-Soriano, J. DeFelipe, L. Alonso-Nanclares, personal communication). Every axonal part closer than 3 μm to a dendrite is detected, and synapses are placed at a 5% subset of these appositions. The subset is chosen such that the number of synapses per connection and synaptic bouton densities match biological values. Spatial distributions of synapses placed in such manner are known to match biological distribution for Endonuclease a number of intracortical pathways with a mean error <8%. All 15,137,757 synapses were modeled using conductance changes. AMPA- and NMDA-type synapses accounted for excitation. For AMPA receptor (AMPAR) kinetics, the synaptic conductance was 0.3 ± 0.2 nS. The rise and decay time constants were 0.2 ± 0.05 ms and 1.7 ± 0.18 ms, respectively. For NMDAR kinetics, conductance was 0.2 ± 0.1 nS with rise and decay times, 0.29 ± 0.23 ms and 43 ± 1.2 ms, respectively. The reversal potential of AMPAR and NMDAR was 0 mV. For inhibitory GABAA synapses, the mean conductance was 0.66 ± 0.2 nS with the rise and decay time constants, 0.2 ± 0.05 ms and 8.3 ± 2.2 ms. Time constant for recovery from depression and time constant for recovery from facilitation were adopted (Angulo et al.