Abstract
Synapses are specialized cell-cell junctions that underlie the function of neural circuits by mediating communication between neurons. Both the formation and function of synapses require tight coordination of signaling between pre- and post-synaptic neurons. Trans-synaptic organizing molecules are important mediators of such signaling. Here we discuss how the EphB and ephrin-B families of trans-synaptic organizing proteins direct synapse formation during early development and regulate synaptic function and plasticity at mature synapses. Finally, we highlight recent evidence linking the synaptic organizing role of EphBs and ephrin-Bs to diseases of maladaptive synaptic function and plasticity.