PT - JOURNAL ARTICLE AU - Esther Krook-Magnuson AU - Gergely G. Szabo AU - Caren Armstrong AU - Mikko Oijala AU - Ivan Soltesz TI - Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy AID - 10.1523/ENEURO.0005-14.2014 DP - 2014 Nov 01 TA - eneuro PG - ENEURO.0005-14.2014 VI - 1 IP - 1 4099 - http://www.eneuro.org/content/1/1/ENEURO.0005-14.2014.short 4100 - http://www.eneuro.org/content/1/1/ENEURO.0005-14.2014.full SO - eneuro2014 Nov 01; 1 AB - Cover Figure Krook-Magnuson et al. report a bidirectional functional connectivity between the hippocampus and the cerebellum in a mouse model of temporal lobe epilepsy, and demonstrate that cerebellar directed on-demand optogenetic intervention can stop seizures recorded from the hippocampus.Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizures. Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures during the chronic phase of the disorder. We further report that the direction of modulation as well as the location of intervention within the cerebellum can affect the outcome of intervention. Specifically, on-demand optogenetic excitation or inhibition of parvalbumin-expressing neurons, including Purkinje cells, in the lateral or midline cerebellum results in a decrease in seizure duration. In contrast, a consistent reduction in spontaneous seizure frequency occurs uniquely with on-demand optogenetic excitation of the midline cerebellum, and was not seen with intervention directly targeting the hippocampal formation. These findings demonstrate that the cerebellum is a powerful modulator of temporal lobe epilepsy, and that intervention targeting the cerebellum as a potential therapy for epilepsy should be revisited.