23 February 2006
John Lisman
Volen Center for Complex Systems
Brandeis University
The problem of the molecular basis of memory is a fundamental unsolved problem in neuroscience. It now appears very likely that memory is encoded by changes in the strength of synapses and that the strength of synapses is determined by the size of the synapse. The diameter of synapses is graded over a large range, varying from 200nm to a micron. The problem is thus how to achieve stability of information storage and how a graded variable can be stored. CaMKII is the major protein of the postsynaptic density. We have explored how bidirectional bistable molecular switches can be contructed through the interaction of the autocatalytic properties of CaMKII and the saturable activity of the PP1 that is also held in the postsynaptic density. We suspect that structural gradation in the size of the synapse is determined by the number of such bistable switches. This hypothesis is being explored by computational, biochemical and anatomical methods.
P Miller, A M Zhabotinsky, J E Lisman, X J Wang,"The stability of a stochastic CaMKII switch: dependence on the number of enzyme molecules and protein turnover", PLoS Biology 3:e107 2005. PubMed