The direct relationship between inhibitory currents and local field potentials.

The frequency profiles of various extracellular field oscillations are known to reflect functional brain states, yet we lack detailed explanations of how these brain oscillations arise. Of particular clinical relevance are the high-frequency oscillations (HFOs) associated with interictal events and the onset of seizures. These time periods are also when pyramidal firing appears to be vetoed by high-frequency volleys of inhibitory synaptic currents, thereby providing an inhibitory restraint that opposes epileptiform spread (Trevelyan et al., 2006, 2007). The pattern and timing of this inhibitory volley is suggestive of a causal relationship between the restraint and HFOs. I show that at these times, isolated inhibitory currents from single pyramidal cells have a similarity to the extracellular signal that significantly exceeds chance. The ability to extrapolate from discrete currents in single cells to the extracellular signal arises because these inhibitory currents are synchronized in local populations of pyramidal cells. The visibility of these inhibitory currents in the field recordings is greatest when local pyramidal activity is suppressed: the correlation between the inhibitory currents and the field signal becomes worse when local activity increases, suggestive of a switch from one source of HFO to another as the restraint starts to fail. This association suggests that a significant component of HFOs reflects the last act of defiance in the face of an advancing ictal event.