synapse formation · Molecular mechanisms of synapse formation and physiology

The present study aims to elucidate how bidirectional signaling systems regulate synapse formation and activity, in vivo. In particular, I will address how repulsive actions of Eph/ephrin signaling during axon pathfinding are overcome and turned into adhesive actions, required for synapse formation and functioning. Therefore, I will study the effects of either stimulation or inhibition of Eph receptor clustering in two different in vivo models and, in an inducible way. Live-imaging of Eph receptors in the zebrafish retinotectal system will enable study of their localization and trafficking, as well as the effect of clustering modulations on the ensuing cellular response. Four different aspects of retinotectal system formation will be evaluated, including topographic mapping and arborization of retinoganglion cells as well as synapse formation and stability. Furthermore, an EphA4 knock-in mouse will be generated to study the effect of clustering during synaptic transmission and on synapse stability in the hippocampus. Therefore morphological, electrophysiological and functional approaches will be used. A final part of this project aims to find downstream signaling effectors that are specifically recruited or activated by lower- or higher order Eph receptor clusters.