Molecules, maps and synapse specificity

A striking feature of the mature central nervous system is the precision of the synaptic circuitry. In contemplating the mature circuitry, it is impos sible to-imagine how more than 20 billion neurons in the human brain become precisely connected through trillions of synapses. Remarkably, much of the final wiring can be established in the absence of neural activity or exper ience; so the algorithms that allow precise connectivity must be encoded la rgely by the genetic programme. This programme, honed over nearly one billi on years of evolution, generates networks with the flexibility to respond t o a wide range of physiological challenges. There are several contemporary models of how synapse specificity is achieved, many of them proposed before the identification of guidance or recognition molecules. Here we review a selection of models as frameworks for defining the nature and complexity of synaptogenesis, and evaluate their validity in view of progress made in id entifying the molecular underpinnings of axon guidance, targeting and synap se formation.