ABIOLOGICAL CLOSED-LOOP SYSTEM IN OPTOGENETIC EXPERIMENTS FOR SUPPRESSION OF EPILEPTIC ACTIVITY
One of the promising options for treating pharmacoresistant forms of epilepsy is low-frequency stimulation of the brain. However, to avoid the side effects, it is required to minimize the stimulation of the brain. This can be achieved if stimulation occurs only at the time of increased probability of the ictal discharge and if it has a specific action on only one type of cells. A way to meet these conditions is to use a closed-loop system between the nervous tissue and a computer in the optogenetic experiment. We have developed a closed-loop system in the optogenetic experiment for effective and harmless suppression of epileptic activity and implemented it in slices of the rat hippocampus and the entorhinal cortex as well as in the primary hippocampal culture. First, we tested the closed-loop system in slices in 4-aminopyridine model of epilepsy. Epileptic activity was detected automatically via monitoring of spiking activity of a representative neuron in the entorhinal cortex. Since a neuron is firing only in response to synaptic input in the used epilepsy model, the spike threshold is a valid indicator of the beginning of epileptic discharge. The software realizing the closed-loop system starts the low-frequency stimulation in response to detection of an epileptic event. Next, we tested the developed system in an optogenetic experiment in culture after expression of channelrhodopsins. These results indicate the potential effectiveness of this approach for the suppression of ictal events