A spatiotemporal model of spine calcium dynamics in the hippocampus
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KeywordsFinite Element Method Spatial Variation Signalling Cascade Synaptic Plasticity Biological Role
Ca2+-signalling in dendritic spines is required for NMDA receptor-dependent synaptic plasticity at glutamatergic synapses in the hippocampus . However, it is not clear whether plasticity induction is dependent solely on the global signal, i.e., the spine volume-averaged Ca2+ signal; or whether plasticity induction is also sensitive to Ca2+-channel nanodomain signaling . A working hypothesis of this work is that temporal and spatial variations in postsynaptic intracellular [Ca2+]-fields may be significant factors governing the signalling cascades that lead to either long-term synaptic potentiation or depression. Direct measurement of [Ca2+] distributions in dendritic spines is experimentally difficult but we can investigate this hypothesis using mathematical models of Ca2+ diffusion.
We have developed a spatio-temporal model of Ca2+ diffusion in three dimensions. We then study our model using finite element methods. The model allows predictions of intracellular [Ca2+]-field responses to combinations of pre- and post-synaptic spikes with nanometre and millisecond spatio-temporal resolution. Our results so far indicate that Ca2+ signalling is highly spatially non-uniform and that Ca2+ signal differences between induction protocols is dependent on location within the spine. This has implications for the ultimate biological role of the Ca2+ signal given that the relevant receptors in the spine are organised inhomogeneously .
Support for this work was provided by the EPSRC, UK (EP/I013717/1).
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