Progress in understanding the biochemical and structural basis of synaptic regulation has been rapid and exciting over the past few years. It has been fueled by the recognition among cell biologists that signaling specificity results from the formation of protein complexes that respond locally and discretely to signals from the membrane surface.
A few synaptic signaling ‘machines’ have now been identified, but many more remain to be characterized before we unravel the intricacies of signal processing in the brain.
We face two major challenges. The first is to understand to what extent the presence
and organization of signaling machinery varies among different synaptic types. This information is crucial because the complement of signaling complexes at a synapse determines the rules by which it integrates and encodes information. The second challenge is to understand how the different signaling pathways interact with and feed back on each other to maintain homeostasis while processing, integrating, and storing rapidly changing information. Efforts to meet this challenge will be aided by promising new strategies for creating and testing spatially accurate computer simulations of com-plex biochemical signaling machinery. We have come a long way toward understanding how synapses work, but we still have far to go.
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