Synapses are not static, but change in strength dependent on their activity. These processes form the cellular basis of learning and memory. Within the postsynaptic neuron, they rely on Calcium influx and the activation of Calcium signalling pathways that can induce either a strengthening or a weakening of the synapse. The balance between strenghtening and weakening is finely tuned. Several of the proteins involved in synaptic Calcium signalling have complex regulatory mechanisms that involve several levels of regulation (e.g.  conformational change, modulator binding, post-translational modifications, localisation).

These different regulation mechanisms co-exist and combine to fine-tune protein activity. Modelling this in detail raises the problem of combinatorial explosion, which can be addressed using rule-based modelling. Here, I present the general problem, discuss different methods for rule-based modelling, and show some results from rule-based models of synaptic protein regulation.