High frequency stimulation can suppress globally seizures induced by 4-AP in the rat hippocampus: An acute in vivo study

Background: High frequency stimulation (HFS) on the hippocampus can locally suppress epileptiform activity in-vitro and decrease seizure frequency in vivo. In-vitro HFS on the ventral commissural tract, a novel target, was shown to block the axonal conduction and suppress activity in the CA1 and CA3 neuron. Objective: To study the spatial extent of seizure suppression by HFS applied on the tract and focus site in an in vivo experiment. Methods: Five adult Sprague-Dawley rats were used for the study. Six electrodes were placed on the septal, middle, and temporal hippocampus bilaterally to simultaneously record seizure activity in the entire hippocampus. Seizure activity was induced by injecting 4-aminopyridine (4-AP) into the right middle part of the hippocampus. Following induction, HFS (100 Hz) was applied to the tract and the focus site at 100, 300 and 500 μA. Results: The induced seizure activity was dominated by two patterns, high frequency spiking and pseudo-periodic spikes. Either tract or focus site stimulation could generate suppression of only the pseudo-periodic spikes. The suppression rates were dependent on stimulation amplitude (P < 0.005, chi square test). However, HFS also caused conversion of the seizure pattern. The conversion rates increased with higher stimulation amplitudes and were higher with focus site stimulation (P < 0.01, Fisher's exact test). Conclusions: The results of this study have two practical implications [1], both tract and focus site stimulation can produce global suppression of hippocampus and [2] the choice of stimulation parameters is critical in order to produce suppression, but not conversion, of seizure pattern.