Matching of pre- and postsynaptic specializations during synaptogenesis.

Formation of chemical synapses in the central nervous system is a highly regulated, multistep process that requires bidirectional communication across the synaptic cleft. Neurotransmitter receptors, scaffolding proteins, and signaling molecules need to be concentrated in the postsynaptic density, a specialized membrane microdomain apposed to the active zone of presynaptic terminals, where transmitter release occurs. This precise, synapse-specific matching implicates that sorting and targeting mechanisms exist for the molecular constituents of different types of synapses to ensure correct formation of neuronal circuits in the brain. There is considerable evidence from in vitro and in vivo studies that neurotransmitter signaling is not required for proper sorting during synapse formation, whereas active neurotransmission is essential for long-term synapse maintenance. Here, the authors review recent studies on the role of cell adhesion molecules in synaptogenesis and on possible mechanisms ensuring correct matching of pre- and postsynaptic sites. They discuss the role of neurotransmitter receptors and scaffolding proteins in these processes, focusing on fundamental differences between synapse formation during development and synapse maintenance and plasticity in adulthood.