Fiber tract stimulation can reduce epileptiform activity in an in-vitro bilateral hippocampal slice preparation

Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease that has been treated with electrical stimulation of gray matter with limited success. However, stimulation of a white matter tract connecting the hippocampi could maximize treatment efficacy and extent. We tested low-frequency stimulation (LFS) of a novel target that enables simultaneous targeting of bilateral hippocampi: the ventral hippocampal commissure (VHC) with a novel in-vitro slice preparation containing bilateral hippocampi connected by the VHC. The goal of this study is to understand the role of hippocampal interplay in seizure propagation and reduction by commissural fiber tract stimulation. LFS is applied to the VHC as extracellular and intracellular recording techniques are combined with signal processing to estimate several metrics of epilepsy including: (1) total time occupied by seizure activity (%); (2) seizure duration (s); (3) seizures per minute (#); and (4) power in the ictal (V(2)Hz(-1)); as well as (5) interictal spectra (V(2)Hz(-1)). Bilateral epileptiform activity in this preparation is highly correlated between hippocampi. Application of LFS to the VHC reduces all metrics of epilepsy during treatment in an amplitude and frequency dependent manner. This study lends several insights into the mechanisms of bilateral seizure reduction by LFS of the VHC, including that depolarization blocking, LTD/LTP and GABA(A) are not involved. Importantly, enhanced post-stimulation 1-Hz spiking correlates with long-lasting seizure reduction and both are heightened by targeting bilateral hippocampi via the VHC. Therefore, stimulating bilateral hippocampi via a single electrode in the VHC may provide an effective MTLE treatment.