Public conference as part of a search committee in Anatomy.

Summary: Recently, excitation/inhibition (E/I) balance was recognized as an important player in brain disorders. Bioactive phospholipids like lysophosphatidic acid (LPA) are synthesized by the astrocytic enzyme autotaxin at the cortical synapse and modulate glutamatergic transmission, and eventually alter E/I balance of cortical networks. We could show that dysregulated LPA signaling alters E/I balance leading to an intermediate phenotype of mental disorders. Moreover, we could show that LPA-related signaling is a critical factor in stroke pathophysiology driving brain damage. Importantly, inhibition of LPA signaling restored E/I balance and significantly improved disease outcome. In addition, our data suggest that LPA signaling affects neuroimmunological disorders and that E/I balance is important in these diseases. In sum, we show that bioactive lipids are novel players in brain disorders.