PROJECT SUMMARY Epilepsy, a condition characterized by chronic, spontaneous seizures, is the fourth most common neurological disorder, affecting nearly 1 in 27 individuals in the United States. In addition to the seizures themselves, chronic epilepsy is associated with cognitive deficits, structural changes, and devastating negative outcomes. For as many as half of all epilepsy patients, seizures are not controlled with current treatment options. There is an urgent need to uncover how chronic epilepsy impacts overall function as well as advance new avenues for therapeutic intervention. Despite not being traditionally associated with epilepsy, the cerebellum is emerging as a potentially critical node in the seizure network; cerebellar structural alterations in epilepsy are associated with comorbidities and negative outcomes, and interventions targeting the cerebellum can powerfully attenuate hippocampal seizures in a mouse model of temporal lobe epilepsy. This bi-directional influence of seizures on the cerebellum and vice versa clearly outline the cerebellum area as a potentially key player in epilepsy, whose yet unknown exact role carries major implications for patients. This proposal leverages a novel technique for mesoscale imaging of the cerebellar cortex to probe how diverse seizure networks alter cerebellar activity, as well as determine whether targeting cerebellar outputs can attenuate seizures arising in structures beyond the hippocampus. By uncovering how the cerebellum interacts with different seizure foci, we will not only gain critical insight into the impact of seizures and chronic epilepsy on cerebellar function, but also potentially uncover new targets for therapeutic modulation in the treatment of different epilepsies. My overarching research interest is to understand computations performed by the cerebellar cortex and how they contribute to healthy behavior and disease. My career goals include becoming an independent researcher studying cerebellar network dynamics and interactions with forebrain structures during motor and non-motor behavior, as well as epilepsy and seizures. My previous training background has given me a solid foundation in electrophysiological recordings, behavioral analyses, optogenetic manipulations, and the implementation of rodent models of epilepsy. However, to fully realize my independent research goals, the training outlined in this K99 will equip me with new skills in experimental techniques and analysis strategies to characterize cellular and network dynamics using calcium imaging. In addition to new technical expertise, this K99 will provide me with a broadened scientific network, improved laboratory management skills, and augmented grant writing expertise. Combined with my prior experience, the additional training and expertise provided by this K99 provides key additions that will help me establish a successful, independent laboratory incorporating innovative, cutting edge research techniques to exp...