Epileptiform activity in the dentate gyrus during low-calcium perfusion and exposure to transient electric fields

1. The dentate gyrus fails to develop epileptiform activity in many experimental models of epilepsy, including the in vitro low-Ca2+ model. Although manipulating the K+ concentration or osmolality of normal low-Ca2+ perfusion mediums can enhance the propensity of the dentate gyrus to develop seizure activity, the specific mechanisms contributing to this change are still under investigation. Identification of these mechanisms should improve our understanding of epileptogenesis and of the factors contributing to the propensity for seizure discharge in other tissues. 2. In the present experiments we used externally generated electric fields to depolarize the somata of large populations of dentate granule cells during exposure to a perfusion medium with no added Ca2+ (low-Ca2+ medium). Uniform electric fields were generated across an individual slice by passing current between two parallel AgCl-coated silver wires placed on the surface of the artificial cerebral spinal fluid. The wires were positioned to straddle the slice such that the current flow was parallel to the dendrosomatic axis of the cell population under investigation. 3. Under control conditions (low-Ca2+ medium, no applied field), stimulation of the dentate hilus evoked a single antidromic population spike in 89% of the slices studied (n = 27). During application of electric fields the same stimulus evoked epileptiform activity in all trials. Well-formed bursts first occurred at an average field intensity of +22.9 +/- 2.5 (SE) mV/mm (n = 24). The amplitude of individual spikes and the total number of spikes, within a burst increased in a graded fashion as the magnitude of the applied field was increased. 4. High field intensities evoked epileptiform activity in the absence of a synchronizing antidromic stimulus. These field-induced bursts occurred after a progressive buildup of rhythmic activity recorded in the extrasomatic space and could persist for the entire duration of an applied field, lasting for several seconds. The average field intensity required to produce a threshold burst was +84.6 +/- 3.6 mV/mm (n = 24). 5. In 11% of trials (3 of 27) the dentate gyrus exhibited poorly developed antidromic bursting without the application of depolarizing electric fields. These bursts were completely suppressed by hyperpolarizing fields in the range of -10 to -20 mV/mm. 6. The results of this investigation support the hypothesis that granule cell sensitivity to nonsynaptic interactions is adequate to support bursting in a normal low-Ca2+ medium, but bursting fails to occur because these cells are normally too hyperpolarized relative to their action potential threshold.(ABSTRACT TRUNCATED AT 400 WORDS)