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Russian
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Article
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530.182
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Effects of the dynamics of noise-induced calcium signals in a biophysical model of the astrocytic process

Autors: 
Ermolaeva Anastasia Viktorovna, Lobachevsky State University of Nizhny Novgorod
Kastalskiy Innokentiy A., Lobachevsky State University of Nizhny Novgorod
Kazantsev Viktor Borisovich, Institute of Applied Physics of the Russian Academy of Sciences
Gordleeva Susanna Yurevna, Lobachevsky State University of Nizhny Novgorod
Abstract: 

The purpose of this work is to study the effects of spatio-temporal dynamics of spontaneous calcium signaling in the morphological structure of an astrocyte at the subcellular level using biophysical mathematical modeling methods.

Methods. This work proposes a biophysical multicompartmental model of noise-induced calcium dynamics in the astrocytic process. The model describes the process of generation of spontaneous Ca2+ signals induced by the stochastic activation of voltage-dependent Ca2+ channels on the plasma membrane of the astrocyte. The model allows us to study the dynamics of the propagation of spontaneous local Ca2+ signals and the mechanisms of formation of spatial Ca2+ patterns in the astrocytic process.

Results. The developed model enables studying the influence of morphology and intracellular biophysical mechanisms on the characteristics of spontaneous noise-induced Ca2+ signaling in the astrocytic process. The parameter ranges at which the model qualitatively reproduces the spontaneous Ca2+ activity at the subcellular level observed in experimental studies have been specified. The characteristics of noise-induced Ca2+ patterns propagating along the process were investigated, depending on the internal structure of the process, its geometry, and the steady state concentration of inositol 1,4,5-triphosphate molecules.

Acknowledgments: 
This work was supported in part by the Ministry of Science and Higher Education of the Russian Federation according to research project No. FSWR-2023-0029 (conceptual model of astrocytic process and model dynamics) and in part by RFBR research project No. 20-32-90151 (development of software for numerical simulations and data analysis).
Reference: 
  1. Semyanov A. Spatiotemporal pattern of calcium activity in astrocytic network // Cell calcium. 2019. Vol. 78. P. 15–25. DOI: 10.1016/j.ceca.2018.12.007.
  2. Li Y. X, Rinzel J. Equations for InsP3 receptor-mediated [Ca2+]i oscillations derived from a detailed kinetic model: a Hodgkin-Huxley like formalism // Journal of theoretical Biology. 1994. Vol. 166, no. 4. P. 461–73. DOI: 10.1006/jtbi.1994.1041.
  3. Ullah G., Jung P., Cornell-Bell A. H. Anti-phase calcium oscillations in astrocytes via inositol (1, 4, 5)-trisphosphate regeneration // Cell calcium. 2006. Vol. 39, no. 3. P. 197–208. DOI: 10.1016/ j.ceca.2005.10.009.
  4. Nett W. J., Oloff S. H., Mccarthy K. D. Hippocampal astrocytes in situ exhibit calcium oscillations that occur independent of neuronal activity // Journal of neurophysiology. 2002. Vol. 87, no. 1. P. 528–37. DOI: 10.1152/jn.00268.2001.
  5. Volterra A., Liaudet N., Savtchouk I. Astrocyte Ca2+ signalling: an unexpected complexity // Nature Reviews Neuroscience. 2014. Vol. 15, no. 5. P. 327–35. DOI: 10.1038/nrn3725.
  6. Skupin A., Kettenmann H., Falcke M. Calcium signals driven by single channel noise // PLoS computational biology. 2010. Vol. 6, no. 8. P. e1000870. DOI: 10.1371/journal.pcbi.1000870.
  7. Oschmann F., Mergenthaler K., Jungnickel E., Obermayer K. Spatial separation of two different pathways accounting for the generation of calcium signals in astrocytes // PLoS computational biology. 2017. Vol. 13, no. 2. P. e1005377. DOI: 10.1371/journal.pcbi.1005377.
  8. De Pitta M., Goldberg M., Volman V., Berry H., Ben-Jacob E. Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes // Journal of biological physics. 2009. Vol. 35. P. 383–411. DOI: 10.1007/s10867-009-9155-y.
  9. Matrosov V. V, Kazantsev V. B. Bifurcation mechanisms of regular and chaotic network signaling in brain astrocytes // Chaos: An Interdisciplinary Journal of Nonlinear Science. 2011. Vol. 21, no. 2. DOI: 10.1063/1.3574031.
  10. Kang M., Othmer H. G. Spatiotemporal characteristics of calcium dynamics in astrocytes // Chaos: An Interdisciplinary Journal of Nonlinear Science. 2009. Vol. 19, no. 3. DOI: 10.1063/1.3206698.
  11. Kazantsev V. B. Spontaneous calcium signals induced by gap junctions in a network model of astrocytes //Physical Review E. 2009. Vol. 79, no. 1. P. 010901. DOI:10.1103/PhysRevE.79.010901. 
  12. Gordleeva S. Y., Stasenko S. V., Semyanov A. V., Dityatev A. E., Kazantsev V. B. Bi-directional astrocytic regulation of neuronal activity within a network // Frontiers in computational neuroscience. 2012. Vol. 6. P. 92. DOI: 10.3389/fncom.2012.00092.
  13. De Pitta M., Volman V., Berry H., Ben-Jacob E. A tale of two stories: astrocyte regulation of synaptic depression and facilitation // PLoS computational biology. 2011. Vol. 7, no. 12. P. e1002293. DOI: 10.1371/journal.pcbi.1002293.
  14. Volman V., Ben-Jacob E., Levine H. The astrocyte as a gatekeeper of synaptic information transfer // Neural computation. 2007. Vol. 19, no. 2. P. 303–26. DOI: 10.1162/neco.2007.19.2.303.
  15. Postnov D. E., Koreshkov R. N., Brazhe N. A., Brazhe A. R., Sosnovtseva O. V. Dynamical patterns of calcium signaling in a functional model of neuron–astrocyte networks // Journal of biological physics. 2009. Vol. 35. P. 425–45. DOI: 10.1007/s10867-009-9156-x.
  16. Bindocci E., Savtchouk I., Liaudet N., Becker D., Carriero G., Volterra A. Three-dimensional Ca2+ imaging advances understanding of astrocyte biology // Science. 2017. Vol. 356, no. 6339. P. eaai8185. DOI: 10.1126/science.aai8185.
  17. Brazhe A., Verisokin A., Verveyko D., Postnov D. Astrocytes: new evidence, new models, new roles // Biophysical Reviews. 2023. P. 1–31. DOI: 10.1007/s12551-023-01145-7.
  18. Wu Y. W., Gordleeva S., Tang X., Shih P. Y., Dembitskaya Y., Semyanov A. Morphological profile determines the frequency of spontaneous calcium events in astrocytic processes // Glia. 2019. Vol. 67, no. 2. P. 246-62. DOI: 10.1002/glia.23537.
  19. Savtchenko L. P., Bard L., Jensen T. P., Reynolds J. P., Kraev I., Medvedev N., Stewart M. G., Henneberger C., Rusakov D. A. Disentangling astroglial physiology with a realistic cell model in silico // Nature communications. 2018. Vol. 9, no. 1. P. 3554. DOI: 10.1038/s41467-018-05896-w.
  20. Gordleeva S. Y., Lebedev S. A., Rumyantseva M. A., Kazantsev V. B. Astrocyte as a detector of synchronous events of a neural network // JETP Letters. 2018. Vol. 107. P. 440–5. DOI: 10.1134/ S0021364018070032.
  21. Gordleeva S. Y., Ermolaeva A. V., Kastalskiy I. A., Kazantsev V. B. Astrocyte as spatiotemporal integrating detector of neuronal activity // Frontiers in physiology. 2019. Vol. 10. P. 294. DOI: 10.3389/fphys.2019.00294.
  22. Kastalskiy I., Ermolaeva A., Kazantsev V., Gordleeva S. Impact of the steady state IP3 level on the intracellular Ca2+ signaling in spatially distributed model of astrocyte // 2020 4th Scientific School on Dynamics of Complex Networks and their Application in Intellectual Robotics (DCNAIR). 2020. P. 120–123. DOI: 10.1109/DCNAIR50402.2020.9216749.
  23. Zeng S., Li B., Zeng S., Chen S. Simulation of spontaneous Ca2+ oscillations in astrocytes mediated by voltage-gated calcium channels // Biophysical journal. 2009. Vol. 97, no. 9. P. 2429– 37. DOI: 10.1016/j.bpj.2009.08.030.
  24. Yaguchi T., Nishizaki T. Extracellular high K+ stimulates vesicular glutamate release from astrocytes by activating voltage-dependent calcium channels // Journal of Cellular Physiology. 2010. Vol. 225, no. 2. P. 512-8. DOI: 10.1002/jcp.22231.
  25. Letellier M., Park Y. K., Chater T. E., Chipman P. H., Gautam S. G., Oshima-Takago T., Goda Y. Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks // Proceedings of the National Academy of Sciences. 2016. Vol. 113, no. 19. P. E2685-94. DOI: 10.1073/pnas. 1523717113.
  26. Zamora N. N., Cheli V. T., Santiago Gonzalez D. A., Wan R., Paez P. M. Deletion of Voltage-Gated Calcium Channels in Astrocytes during Demyelination Reduces Brain Inflammation and Promotes Myelin Regeneration in Mice. The Journal of Neuroscience. 2020. Vol. 40, no. 17. P. 3332–3347. DOI: 10.1523/JNEUROSCI.1644-19.2020. 
  27. Hodgkin A. L., Huxley A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve // The Journal of physiology. 1952. Vol. 117, no. 4. P. 500–544. DOI: 10.1113/jphysiol.1952.sp004764.
  28. Dupont G., Goldbeter A. One-pool model for Ca2+ oscillations involving Ca2+ and inositol 1,4,5-trisphosphate as co-agonists for Ca2+ release // Cell calcium. 1993. Vol. 14, no. 4. P. 311–22. DOI: 10.1016/0143-4160(93)90052-8.
  29. Gordleeva SY, Matrosov VV, Kazantsev VB. Calcium oscillations in astrocytes. Part 1 Astrocyte as generator of calcium oscillations. Izvestiya VUZ. Applied Nonlinear Dynamics. 2012;20(3):29–39. DOI: 10.18500/0869-6632-2012-20-3-29-39.
  30. Cresswell-Clay E., Crock N., Tabak J. and Erlebacher G. A Compartmental Model to Investigate Local and Global Ca2+ Dynamics in Astrocytes // Frontiers in Computational Neuroscience. 2018. Vol. 12. P. 94. DOI: 10.3389/fncom.2018.00094.
  31. Verisokin A. Y., Verveyko D. V., Postnov D. E., Brazhe A. R. Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics // Frontiers in Cellular Neuroscience. 2021. Vol. 15. P. 645068. DOI: 10.3389/fncel.2021.645068.
  32. Santello M., Toni N., Volterra A. Astrocyte function from information processing to cognition and cognitive impairment // Nature neuroscience. 2019. Vol. 22, no. 2. P. 154–66. DOI: 10.1038/s41593- 018-0325-8.
  33. Popov A., Brazhe A., Denisov P., Sutyagina O., Li L., Lazareva N., Verkhratsky A., Semyanov A. Astrocyte dystrophy in ageing brain parallels impaired synaptic plasticity // Aging cell. 2021. Vol. 20, no. 3. P. e13334. DOI: 10.18500/0869-6632-2012-20-3-29-39.
  34. Olabarria M., Noristani H. N., Verkhratsky A., Rodrıguez J. J. Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer’s disease // Glia. 2010. Vol. 58, no. 7. P. 831–8. DOI: 10.1002/glia.20967.
Received: 
01.03.2024
Accepted: 
21.05.2024
Available online: 
24.09.2024