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Three-dimensional Computational Modeling of Cellular Calcium Dynamics in Healthy and Pathological Neurons

Markus Breit1, Anna Hagenston2, Andrea Hellwig2, Peter Bengtson2, Hilmar Bading2 and Gillian Queisser1*
  • 1 University of Frankfurt, Goethe-Center for Scientific Computing, Germany
  • 2 University of Heidelberg, Interdisciplinary Center for Neuroscience, Germany

In the light of pathological diseases, such as Alzheimer’s, more and more significance has been attributed to cellular calcium signaling in neurons in the last years. Cellular calcium is regulated by a complex system of channels which allow the exchange of calcium between extracellular space and the cytosol and the exchange between cytosol and endoplasmic reticulum (ER) (Berridge, 2002) (or other organelles such as mitochondria). Further sources of intracellular calcium are active synapses which regulate NMDA-gated calcium levels and produce enzymatically regulated inositol-3-phosphate (IP3). This molecule interacts with the calcium relevant IP3-receptor embedded in the ER-membrane (Foskett et al. 2007). Pathologies like Alzheimer’s can disrupt this delicate system at multiple levels.We are currently developing a cellular calcium model including the realistic three-dimensional morphology of neurons (using automatic reconstruction methods (Broser et al., 2004, Queisser et al., 2008) and their calcium-relevant components, such as calcium-regulating channels on the plasma membrane, calcium-exchange mechanisms on the endoplasmic membrane, the biophysics of cytosolic and endoplasmic calcium, as well as the cell nucleus. The biophysical model is based on continuum mechanics derived systems of partial differential equations which are solved on the simulation platform uG (Ref). This work is based on previous calcium modeling studies within neuron nuclei, (Wittmann et al., 2010).This cellular model is intended to describe the nuclear response to a wide range of cellular configurations. In particular one is able to extract differences in nuclear responses between healthy and pathological neurons.

References

Berridge MJ (2002) The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 32: 235-249.

Foskett JK, White C, Cheung K-H and Mak DOD (2007) Inositol Trisphosphate Receptor Ca2+ Release Channels. Physiol. Rev. 87:593-658

Broser PJ, Schulte R, Lang S, Roth A, Helmchen F, Waters J, Sakmann B and Wittum G (2004) Nonlinear anisotropic diffusion filtering of three- dimensional image data from two-photon microscopy. J Biomed Opt 9:1253–1264

Queisser, G., Wittmann, M., Bading, H., and Wittum, G (2008) Filtering, reconstruction, and measurement of the geometry of nuclei from hippocampal neurons based on confocal microscopy data. Journal of Biomedical Optics 13, 014009

Bastian, P., and Wittum, G. (1994). Robustness and adaptivity: The UG concept. In P. Hemker, P. Wesseling (Eds.), Mul- tigrid Methods IV. Proceedings of the Fourth European Multigrid Conference, Amsterdam 1993. Basel: Birkhäuser.

Wittmann, M., Queisser, G., Eder, A., Wiegert, J.S., Bengtson, C.P., Hellwig, A., Wittum, G., and Bading, H (2009) Synaptic Activity Induces Dramatic Changes in the Geometry of the Cell Nucleus: Interplay Between Nuclear Structure, Histone H3 Phosphorylation, and Nuclear Calcium Signaling. The Journal of Neuroscience 29(47):14687-14700

Keywords: computational neuroscience

Conference: Bernstein Conference on Computational Neuroscience, Berlin, Germany, 27 Sep - 1 Oct, 2010.

Presentation Type: Presentation

Topic: Bernstein Conference on Computational Neuroscience

Citation: Breit M, Hagenston A, Hellwig A, Bengtson P, Bading H and Queisser G (2010). Three-dimensional Computational Modeling of Cellular Calcium Dynamics in Healthy and Pathological Neurons. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference on Computational Neuroscience. doi: 10.3389/conf.fncom.2010.51.00076

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Received: 14 Sep 2010; Published Online: 23 Sep 2010.

* Correspondence: Dr. Gillian Queisser, University of Frankfurt, Goethe-Center for Scientific Computing, Frankfurt, Germany, gillian.queisser@gcsc.uni-frankfurt.de