Molecules, Networks, and Memory
A profound evolution of modeling scope and scale has occurred in the field as we have sought to understand how memory works at the level of molecular networks. We have moved from an initial concept of a small number of relatively simple syn-aptic functions to the current appreciation of the complexity of function and cellular mechanisms that support these functions.
One of the initial triumphs of the field was to find a molecular correlate of the crucial property of Hebbian associativity . A list of further functional modules of the synapse might include the detection and selection of memory-triggering activity patterns; chemical circuits that store information through feedback and switching; presynaptic release control; movement of key molecules into and out of the synapse; and activity-triggered protein synthesis (Fig. 1). More recent data suggest further modules for the formation and maintenance of synaptic contacts and pre- and postsynaptic structure. This long list of synaptic functions may suggest a pessimistic view of our ability to either complete the list or understand the signaling mechanisms. I propose, instead, that the list is a roadmap, and hence a clear statement of where modeling studies need to go. The system is undoubtedly complex, and therein lies the challenge for the field. Typical models for these functional modules contain tens to hundreds of molecular species and reactions. In keeping with the theme of this symposium and book, I suggest that the challenge of biological complexity is best met squarely, by developing models that embrace the complexity but are not overwhelmed by it. This systematic process of model building, one synaptic function at a time, is the basis for an eventual quantitative understanding of the synapse and its role in memory.
KeywordsAMPA Receptor Functional Module Synaptic Function Pattern Selectivity Bistable Switch
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