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Spatiotemporal molecular dynamics and synaptic plasticity
BMC Neuroscience volume 9, Article number: P103 (2008)
Calcium levels in spines play a significant role in determining the sign and magnitude of synaptic plasticity. Recent experiments using calcium sensitive dyes have allowed measurements of calcium transients in whole spines, however experimental resolution does not allow imaging of the spatial distribution of calcium within the spine [1, 2, 5]. Calcium can activate Calcineurin or bind to CaM and consequently activate CaMKII which is key mediator of synaptic plasticity. A main source of calcium influx into the spine is from the NMDA receptors. There are four different subtypes of NR2 subunits of NMDA receptors, NR2A/B/C/D. In the mature cortex the majority of the synaptic NMDA receptors are constituted by NR1/NR2A and in the immature cortex by NR1/NR2B. Experiments have shown that the subunit composition of NMDA receptors has an influence on the sign of synaptic plasticity, but different experiments resulted in different and possibly conflicting results [3, 4]. NR2B has slower kinetics and higher affinity for Glutamate than that of NR2A. In addition NR2B receptors have a binding site for CaMKII.
Abstract models for synaptic plasticity typically assume a single compartmental model for describing molecular dynamics and consequently for describing synaptic plasticity [5, 6]. The main question that we address in that paper is, "Is a single compartmental equation sufficient for describing calcium dynamics with respect to synaptic weight changes?"
For our purpose, we simulated the spatiotemporal dynamics of Calcium and Calmodulin by using a multi compartmental model of the spine head including the neck. We also simulated an intrinsic calcium buffer and calcium pumps on the surface of the spine. Calcium pumps and as well as NMDA receptors were simulated by Markov models . Using this model we can observe the spatiotemporal distribution of calcium and calcium-calmodulin transients. We find that the calcium pumps as well as the geometry of the neck affect the spatiotemporal dynamics of calcium and consequently of calmodulin, and that different NMDA receptor subunits differentially affect this distribution. Combining an abstract plasticity rule , which depends on calcium concentration, and the results of the calcium dynamics from our simulations, we demonstrate that a simple one compartmental ODE is usually sufficient for describing calcium dynamics at the spine for induction of plasticity.
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Kalantzis, G., Shouval, H.Z. Spatiotemporal molecular dynamics and synaptic plasticity. BMC Neurosci 9, P103 (2008). https://doi.org/10.1186/1471-2202-9-S1-P103
- NMDA Receptor
- Synaptic Plasticity
- Compartmental Model
- Spatiotemporal Dynamic
- NMDA Receptor Subunit