Dissociation between mossy fiber sprouting and rapid kindling with low-frequency stimulation of the amygdala

Abstract

In an attempt to determine whether sprouting of mossy fibers is invariably correlated with kindling of seizures, we subjected rats to rapid kindling with long trains of low-frequency stimulation of the amygdala that resulted in development of generalized seizures within a mean of five stimulations. For comparison, we subjected other rats to conventional kindling with short trains of high-frequency stimulation of the amygdala that resulted in development of generalized seizures within a mean of 13 stimulations. We found no evidence of mossy fiber sprouting in the dentate gyrus of rats killed one day after completion of rapid kindling, as compared to yoked controls, although significant sprouting was seen in rats killed one day after completion of conventional kindling. When we examined tissue from rats killed 20 days after rapid kindling, however, we did find significant sprouting, suggesting that mossy fiber sprouting can be triggered by rapid kindling if sufficient survival time is allowed. The observed disparity between completion of rapid low-frequency kindling and detection of mossy fiber sprouting suggests that mossy fiber sprouting may be associated more with sustained survival time after neuronal activation than with kindling per se. Furthermore, the similar time course of conventional kindling and of mossy fiber sprouting obscures the determination of a causal role of mossy fiber sprouting in conventional kindling.