| Autor: |
Proskurina EY; Almazov National Medical Research Centre, 2 Akkuratova Street, 197341 St. Petersburg, Russia.; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 44 Toreza Prospekt, 194223 St. Petersburg, Russia., Chizhov AV; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 44 Toreza Prospekt, 194223 St. Petersburg, Russia.; Computational Physics Laboratory, Ioffe Institute, 26 Polytekhnicheskaya Street, 194021 St. Petersburg, Russia.; MathNeuro Team, Inria Centre at Universite Cote d'Azur, 06902 Sophia Antipolis, France., Zaitsev AV; Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 44 Toreza Prospekt, 194223 St. Petersburg, Russia. |
| Abstrakt: |
Low-frequency electrical stimulation is used to treat some drug-resistant forms of epilepsy. Despite the effectiveness of the method in suppressing seizures, there is a considerable risk of side effects. An optogenetic approach allows the targeting of specific populations of neurons, which can increase the effectiveness and safety of low-frequency stimulation. In our study, we tested the efficacy of the suppression of ictal activity in entorhinal cortex slices in a 4-aminopyridine model with three variants of low-frequency light stimulation (LFLS): (1) activation of excitatory and inhibitory neurons (on Thy1-ChR2-YFP mice), (2) activation of inhibitory interneurons only (on PV-Cre mice after virus injection with channelrhodopsin2 gene), and (3) hyperpolarization of excitatory neurons (on Wistar rats after virus injection with archaerhodopsin gene). Only in the first variant did simultaneous LFLS of excitatory and inhibitory neurons replace ictal activity with interictal activity. We suggest that LFLS caused changes in the concentration gradients of K + and Na + cations across the neuron membrane, which activated Na-K pumping. According to the mathematical modeling, the increase in Na-K pump activity in neurons induced by LFLS led to an antiepileptic effect. Thus, a less specific and generalized optogenetic effect on entorhinal cortex neurons was more effective in suppressing ictal activity in the 4-aminopyridine model. |
