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A spatiotemporal model of spine calcium dynamics in the hippocampus

Ca2+-signalling in dendritic spines is required for NMDA receptor-dependent synaptic plasticity at glutamatergic synapses in the hippocampus [1]. 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 [2]. 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 [3].

References

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    Malenka RC, Bear MF: LTP and LTD: an embarrassment of riches. Neuron. 2004, 44 (1): 5-21.

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    Chen Y, Sabatini BL: Signaling in dendritic spines and spine microdomains. Current Opinion in Neurobiology. 2012, 22 (3): 389-396.

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    Mori MX, Erickson MG, Yue DT: Functional stoichiometry and local enrichment of calmodulin interacting with Ca2+ channels. Science. 2004, 304 (5669): 432-435.

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Acknowledgements

Support for this work was provided by the EPSRC, UK (EP/I013717/1).

Author information

Correspondence to Thom Griffith.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Keywords

  • Finite Element Method
  • Spatial Variation
  • Signalling Cascade
  • Synaptic Plasticity
  • Biological Role