, 2000) and assigned to each putative inhibitory synaptic location identified by the collision-detection algorithm. The GABAA reversal was −80 mV. External GSK1210151A mw input is mediated by distributing additional excitatory and inhibitory synapses randomly (uniform distribution) across all cells and activating them independently with a temporally modulated frequency. External synapses accounted

for approximately 5% of the total number of synapses. To measure spiking synchrony, we calculated the mean of the normalized joint peristimulus time (PST) histogram at a lag of 0 ms, i.e., the mean cross-covariance of PST histograms of cell pairs, normalized by the product of their SD. To generate the histograms, we used a bin width of 1 ms. As the covariance would be affected by the change in firing rates between simulated UP and DOWN, we limited the analysis to spikes elicited during UP. To remove synchrony from the simulation (uncorrelated case), we first generated artificial spike trains by moving all spikes of the control case

to times randomly chosen between 0 and 4,000 ms. This generated independent stationary Poisson spike trains with the same number SCH727965 price of spikes as in the control case. This spike train was then used to drive synapses in a simulation. The external input was also present but with a constant rate equal to the mean of the rate in the control case. To increase synchrony (supersynchronized case), we moved all spike times of the control case to the nearest multiple of 5 ms. External input in this case was identical to the control case. The extracellular contribution of transmembrane currents of all neural compartments (approx. 410 compartments per cell, >5,000,000 in total) was calculated via the line source approximation, LSA (Holt and Koch, 1999). Briefly, assuming a purely homogeneous and resistive (3.5 Ω m) extracellular medium, Laplace’s equation applies ∇2Ve = 0. At the boundaries, (1/ρ)Ve = Jm with ρ being the resistivity and Jm the transmembrane current density. LSA assumes each cylindrical compartment of the spatially discretized neuron as a line (a cylinder of infinitesimally small diameter) with a constant current density along the line. The Ve

contributed by Resminostat current I  j of each neural compartment j   evenly distributed over the line segment of length Δs  j and the overall extracellular voltage Ve(r→,t) becomes Ve(r→,t)=∑j=1NρIj(t)4πΔsjloghj2+rj2−hjlj2+rj2−lj,with rj being the radial distance from line segment, hj the longitudinal distance from the end of the line segment, and lj = Δsj+hj the distance from the start of the line segment. The LSA was found to be accurate, except at very small distances (a few micrometers) from the cable. Calculation of Ve using the LSA took place on a separate computer cluster (SGI) and took approx. 1 hr. The CSD was estimated as the negative second spatial derivative along the depth axis. We also calculated the CSD via iCSD (Łęski et al., 2011), and the outcome remained very similar.