Magnetogenetic closed-loop reduction of seizure activity in a rat model of epilepsy

Abstract

On-demand neurostimulation has shown success in epilepsy patients with pharmacoresistant seizures. Seizures produce magnetic fields that can be recorded using magnetoencephalography. We developed a new closed-loop approach to control seizure activity based on magnetogenetics using the electromagnetic perceptive gene (EPG) that encodes a protein that responds to magnetic fields. The EPG transgene was expressed in inhibitory interneurons under hDlx promoter and kainic acid was used to induce acute seizures. In vivo electrophysiological signals were recorded. We found that hDlx EPG rats exhibited a significant delay in the onset of first seizure (1142.72 ± 186.35s) compared to controls (644.03 ± 15.06s) and significantly less seizures (4.11 ± 1.03) compared to controls (8.33 ± 1.58). These preliminary findings suggest that on-demand activation of EPG expressed in inhibitory interneurons suppress seizure activity, and magnetogenetics via EPG may be an effective strategy to alleviate seizure severity in a minimally invasive, closed-loop and cell-specific fashion.

A putative design for the electromagnetic activation of split proteins for molecular and cellular manipulation

“…Several approaches have shown effective magnetic activation of cellular functions by ion channel interactions ( Huang et al, 2010 ; Stanley et al, 2012 ; Stanley et al, 2015 ; Wheeler et al, 2016 ). A novel electromagnetic perceptive gene (EPG) from the glass catfish Kryptopterus vitreolus has also been shown to have a response to changes in magnetic fields ( Krishnan et al, 2018 ; Cywiak et al, 2020 ; Hwang et al, 2020 ; Metto et al, 2022 ).…”