Piret Kleis: Low frequency stimulation for seizure control in experimental epilepsy
| When |
Jul 09, 2024
from 05:15 PM to 05:45 PM |
|---|---|
| Where | Bernstein Center, Lecture Hall, ground floor, Hansastr. 9a |
| Contact Name | Gundel Jaeger |
| Contact Phone | 0761 203 9549 |
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Abstract
Mesial temporal lobe epilepsy (MTLE) is the most common form of drug-resistant epilepsies in adults, characterized by focal seizures originating from the hippocampus and surrounding structures. Neurostimulation provides an alternative to surgery-ineligible patients with intractable seizures. However, commonly applied high-frequency stimulation tends to have variable outcomes on seizure reduction, outlining the need for refining stimulation parameters and targets. Hippocampal low-frequency stimulation (LFS) has shown antiepileptic effects in animal studies and small clinical cohorts, yet the optimal cellular targets, long-term effects, and mechanisms of LFS remain unclear.
To systematically investigate the effects of LFS, we use the intrahippocampal kainate mouse model that recapitulates the main pathological features of MTLE: recurrent spontaneous seizures, hippocampal sclerosis, and cognitive comorbidities. We first applied optogenetic stimulation at four different neuron populations to determine the optimal target in the entorhinal-hippocampal circuit for suppressing seizures by LFS. Next, we used clinically translatable electrical LFS in the sclerotic hippocampus, identified as the best LFS target in the last step. We compared three stimulation modes, continuous, discontinuous, and on-demand, and picked the continuous LFS to examine its long-term effects. Our newest results delineate how long-term LFS in chronically epileptic mice affects focal and generalized seizures, spatial learning and memory, and structural plasticity at the perforant path-dentate granule cell synapse.