Fox, John E., Marom Bikson, and John G. R. Jefferys. Tissue resistance changes and the profile of synchronized neuronal activity during ictal events in the low-calcium model of epilepsy. J Neurophysiol 92: 181-188, 2004. First published March 3, 2004 10.1152/ jn.00123.2004. Population spikes vary in size during prolonged epileptic ("ictal") discharges, indicating variations in neuronal synchronization. Here we investigate the role of changes in tissue electrical resistivity in this process. We used the rat hippocampal slice, lowCa 2ϩ model of epilepsy and measured changes in pyramidal layer extracellular resistance during the course of electrographic seizures. During each burst, population spike frequency decreased, whereas amplitude and spatial synchronization increased; after the main discharge, there could be brief secondary discharges that, in contrast with those in the primary discharge, started with high-amplitude population spikes. Mean resistivity increased from 1,231 ⍀.cm immediately before the burst to a maximum of 1,507 ⍀.cm during the burst. There was no significant increase during the first 0.5-1 s of the field burst, but resistance then increased ( ϳ 5 s), reaching its peak at the end of the burst, and then decayed slowly ( ϳ 10 s). In further experiments, we modulated the efficacy of electrical field effects by changing perfusate osmolarity. Reducing osmolarity by 40 -70 mOsm increased preburst resistivity by 19%; it reduced minimum population spike frequency (ϫ0.6 -0.7) and increased both maximum population spike amplitude (ϫ1.5-2.3) and spatial synchronization (ϫ1.4 -2.5, crosscorrelation over 0.5 mm) during bursts. Increasing osmolarity by 20 -40 mOsm had the opposite effects. These results suggest that, during each field burst, field effects between neurons gradually become more effective as cells swell, thereby modulating burst dynamics and facilitating the rapid synchronization of secondary discharges.