Epilepsy affects over 50 million people worldwide, yet 30% of patients have seizures refractory to current treatments. Precision therapies like optogenetics, chemogenetics, and photopharmacology offer the potential for more targeted, effective treatments. This project aims to systematically evaluate these cutting-edge approaches in well-established preclinical models of epilepsy. We will test therapeutic effects of expressing and/or activating DREADDs, opsins and/or photoactive drugs using video-EEG monitoring inj rodents. Cognitive and behavioral side effects will also be examined.We hypothesize that focal inhibition of the seizure focus will suppress seizure activity with high spatiotemporal precision while minimizing off-target effects. This preclinical evaluation of feasibility, efficacy and safety is a critical step towards translating these novel therapies into improved treatment options for patients with refractory epilepsy.