Structural dynamics of synapses and synaptic components.

Learning and memory formation are apparently based on cascades of molecular and cellular processes with increasing time constants (ms to days and weeks), but even the most long-lasting effects are transient. Memory traces may permanently modify the behavior (activity patterns, gene expression) of neurons and neuronal networks. Therefore the question is raised whether our current view on the stability of synapses under normal conditions is tenable. Evidence is reviewed suggesting that as direct or indirect effects of modifications in bioelectrical activity and chemical trophicity, synapses may be remodeled and removed within days and weeks, and possibly within hours. Accordingly, species-specific connectivity patterns are not restricted to the standard architecture of the CNS, but (morpho-)genetics allow for a considerable number of alternative wiring patterns, which appear under unusual conditions during ontogenesis and in adulthood. Our present knowledge suggests that, rather than the formation of synapses, they are a selective process. Until now there is no direct method of measuring either synaptic reorganization or the average life span of synapses. Specific cases, however, allow to estimate synapse turnover during ontogenesis, at its lowest possible level. Such data suggest that each synapse is on average remodeled or replaced several to many times during normal developmental, e.g. in the cerebral cortex of Marmoset monkeys at the very least 5 to 10 times (corresponding to 250 million synapses eliminated per hour in area 17!). It is discussed how the consequences of synapse turnover could be utilized by learning processes. Conclusions are followed by an outlook.