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Identification of optimal stimulation targets to suppress seizures in a mouse model of epilepsy

Funded by the German Research Foundation (HA 1443/12-1)

Funding to Prof. Dr. Carola Haas

Project Description

Mesial temporal lobe epilepsy (MTLE) is a common form of drug-resistant epilepsy in adults, characterized by focal seizures originating from the hippocampus or entorhinal cortex. Deep brain stimulation shows promise for alleviating intractable seizures. However, commonly applied high-frequency stimulation tends to have low efficacy in patients with hippocampal sclerosis (HS), showing the need for refining stimulation parameters and targets. Our previous research demonstrated that low-frequency stimulation (LFS) of entorhinal afferents in the sclerotic hippocampus reduced seizures in epileptic mice with HS (Paschen et al., eLife, 2020). In this project, we aim to identify the critical cell population responsible for this anti-epileptic effect. Our study compares the seizure-suppressive potential of optogenetic LFS in four targets: (1) entorhinal afferents in the sclerotic dorsal hippocampus, (2) principal cells in the medial entorhinal cortex (mEC), (3) dentate granule cells (DGCs) in the sclerotic dorsal hippocampus, and (4) DGCs in the non-sclerotic intermediate hippocampus. To induce chronic epilepsy, we administer unilateral intrahippocampal kainate injections in mice and target specific cell populations using Channelrhodopsin2 (ChR2) and optic fiber implantation. We record intracranial activity from freely moving epileptic mice for three hours with and without optogenetic LFS.