From contact to connection: early events during synaptogenesis.

When neuronal processes first come into contact, chemical synapses can form rapidly. Many neurons synthesize synaptic machinery through intrinsic programs before cell-cell interactions. During the formation of chemical synapses, contact with appropriate targets has been found to trigger intracellular signals that induce the assembly of pre-existing synaptic machinery. We propose that 'promiscuous' neurons secrete transmitter before contacting their targets, and form over-abundant synapses, which undergo additional activity-dependent refinement; 'selective' neurons, which retain their original connectivity, require concerted retrograde and anterograde signaling to ensure their correct matching.