Simplified biochemical model of synaptic plasticity, extended with Calcium-Induced Calcium Release

Abstract

Synaptic plasticity is a cellular process that leads to strengthening (LTP) or weakening(LTD) of a neuronal synapse and is highly associated with learning and memory. These events are dependent on calcium entering the cell: high calcium influx activates the CaMKII pathway that leads to LTP, whereas low influx triggers the calcineurin pathway that leads to LTD. The outcome of these cascades is represented by phosphorylation of AMPA receptors, prevalent feature of LTP. This model represents the aforementioned biochemical mechanisms based on calcium concentrations and it is a simplified version of Li et al (2012)* model of synaptic plasticity. Additionally, it was extended by the addition of a pathway activated by glutamate binding to mGluR5 that leads to calcium-induced calcium release, through activation of IP3 receptors. This extended version better depicts calcium dynamics in the cell. Both models can be found as SBML files and they were originally created to run in COPASI software. Simulations can be run as time courses (here of 500 sec) or parameter scans for various molecular concentrations. Apart from my co-authors whom I'd like to thank for their support and contribution to this model, I am very grateful to Richard Fitzpatrick for his precious advice and help during my project. *Li et al. (2012) "Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII". PLoS One. 2012; 7(9): e43810. doi: 10.1371/journal.pone.0043810