, 2006) demonstrates that our single-neuron representations accurately reproduce the EAP waveform even though their reconstruction was optimized to reproduce intracellular rather than extracellular events (Hay et al., 2011). In fact, accurate simulation of the EAP waveform can be used as an selleck compound additional (and often stricter) measure for the quality of the reconstruction of a

neuron, especially for perisomatic compartments (Gold et al., 2007). The prevailing view is that the LFP primarily reflects postsynaptic currents for frequencies lower than approximately 100–150 Hz (Nunez and Srinivasan, 2006), which stems from the recognition that extracellular currents from many individual compartments must overlap in time to induce a measurable signal, with such overlap primarily occurring for synaptic events (Elul, 1971 and Logothetis and Wandell, 2004). This assumption, in turn, has motivated the study of LFPs using models that account for morphologically realistic but passive neurons with the statistics of postsynaptic currents and their spatial distribution emulating experimental observations. Yet, the presence of active conductances along the neural membrane is a highly nonlinear (either Vorinostat voltage- or ion-dependent) contributor of extracellular

currents that cannot be accounted for via passive elements. Figure 2 shows the outcome of a large-scale simulation in which slow (1 Hz) external excitatory (AMPA and NMDA) and inhibitory (GABAA) synaptic activity impinged along both L4 and L5 pyramidal neurons (Figure 2A). For the active membrane simulation, this elicits spiking (Figure 2B), Ketanserin which, in turn, gives rise to local and global postsynaptic activity (Figures 2C and 2D). We define the depolarizing (hyperpolarizing) part of the external 1 Hz stimulation as UP (DOWN) state. The spike frequency (Figure 2D) of the different cell types considered in our simulations agrees with experimental observations in rodents during SWA (Fanselow and Connors, 2010, Haider et al.,

2006, Luczak et al., 2007, Luczak et al., 2009 and Sanchez-Vives and McCormick, 2000). To understand the different components contributing to the LFP, we considered three scenarios, each of which has identical spatiotemporal postsynaptic currents (PSC). We define the PSC to be the postsynaptic membrane current flowing at the synapse in response to the synaptic-associated conductance change, Isyn(t) = gsyn(t)(Vm-Vrev), with gsyn being the synaptic conductance, Vm is the membrane potential, and Vrev is the reversal potential (Koch, 1999). In the first scenario, we only consider the LFP caused by these currents from the roughly 15 million synapses (Figure 2E) by ignoring all nonsynaptic currents in the calculation of the LFP.