Migraine is a disabling brain disorder with major consequences to patients and society. Diverse genetic and physiological factors predispose for attacks, stressing the need for a multidisciplinary approach. In the host team at the LUMC, the Netherlands, migraine research led to identification of the first migraine genes and generation of transgenic mice harboring mutations that cause hemiplegic migraine in patients. An important focus of research at the host is on cortical spreading depression (CSD), the correlate of a migraine aura capable of triggering pain. The migraine mouse models of the host revealed increased neurotransmission resulting in enhanced susceptibility to CSD and other migraine-relevant phenotypes. Underlying mechanisms are not well understood, in regarding neuronal network function in migraine. A Marie Curie CIG will provide excellent support to use my expertise with monitoring neuronal network function and brain pH in these migraine mice in the multidisciplinary research setting of the host. The central question to my research is how sudden changes in brain physiology culminate in a migraine attack. My specific objectives are to (i) gain insight in changes in cortical network activity underlying CSD in freely moving migraine mice and study the role of external influences such as stress and sleep (ii) identify changes in sensory processing that make migraine mice susceptible to CSD, and (iii) investigate whether increased susceptibility to CSD in migraine mouse mutants relates to metabolic disturbances at the network and cellular level. My research will provide insight on changes in cortical function and sensory processing preceding and following CSD events in migraine mice which will help understand how pain mechanisms are activated in migraine. Such knowledge is needed to improve therapeutic strategies. To ensure coherent translation of our experimental findings to the patient, my research will be tightly regulated by feedback from the clinic.