PROJECT SUMMARY A major obstacle for the identification and characterization of new therapies for migraine and pain has been limitations of the animal models used to study these therapies. We have developed a novel approach that addresses this obstacle: a minimally invasive skull-attached microchip-based system and video recording/analysis system that enables continuous recording and triggering of neurovascular activity and behavior over months. We will further develop and validate this approach as a novel platform for the discovery and characterization of migraine therapies. We will: 1. Quantify a comprehensive set of neurovascular and behavioral responses to established human migraine triggers and cortical spreading depression (CSD) using the microchip/video platform. 2. Use the microchip/video platform to characterize the effects of acute migraine therapies on the response to established migraine triggers and CSD to validate the platform as a useful tool for the discovery and characterization of acute therapies 3. Use the microchip /video platform to characterize the effects of migraine preventive therapies. Key findings will be independently replicated at two different institutions. The platform described in this proposal represents a significant advance in our efforts to find new approaches to the treatment of migraine, a highly prevalent and disabling nervous system disorder.