MODELLING THE INFLUENCE OF SPATIALLY DISTINCT CALCIUM SOURCES ON CAMODULIN AND CAMKII ACTIVITY

Synaptic plasticity, the change in the strength of communication between two neurons, is the foundational mechanism of learning in the brain. Experimental studies have identified several phenomena, including the Bienenstock-Cooper-Munroe model, STDP and BTSP, which build the basis for plasticity models in systems neuroscience. However, all these observations are caused by the activities of several intracellular proteins like Calmodulin (CaM) and CaMKII, which are dependent on the local calcium concentration. Therefore, not only is the temporal progression of calcium influx important for the underlying processes resulting in plastic changes of the synapse, but also its spatial gradient. Calcium can enter the postsynapse through calcium channels like NMDA- and VDCC-channels from the extracellular space. Another source of calcium is the endoplasmic reticulum through cascades involving its IP3- and RyR-receptors. In this computational project, we investigate the influence of these two spatially-distinct calcium sources, postsynaptic channels and intracellular stores, on the downstream protein activity within the plasticity cascade. We demonstrate that due to ER-recruitment and spatial co-location, protein activity and consequently plasticity predictions differ. Overall, this work shows that synaptic plasticity is subject to spatial-temporal calcium dynamics and is the first step towards a detailed characterisation of the signal transduction along the intracellular plasticity cascade.