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Sunday, July 19 • 9:00pm - 10:00pm
P116: Astrocyte simulations with realistic morphologies reveal diverse calcium transients in soma and processes

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Zoom: https://tuni.zoom.us/j/63203945445


Ippa Seppala
, Laura Keto, Iiro Ahokainen, Nanna Förster, Tiina Manninen, Marja-Leena Linne

The role of astroglia has long been overlooked in the field of computational neuroscience. Lately their involvement in multiple higher-level brain functions, including neurotransmission, plasticity, memory, and neurological disorders, has been found to be more significant than previously thought. It has been hypothesised that astrocytes fundamentally affect the information processing power of the mammalian brain. As the glia to neuron ratio increases when moving from simpler organisms to those more complex, it is clear that more attention should be directed to glial involvement. Despite the recent advances in neuroglial research there still exists a lack of glia-specific computational tools. Astroglia differ considerably from neurons in their morphology as well as their biophysical functions [1], making it difficult to acquire reliable simulation results with simulators made for studying neuronal behaviour. As the differences in cellular dynamics of astrocytes compared to those of neurons are significant, there clearly exists a need for tailored methods for simulating the behaviour of glial cells.

One such astrocyte specific simulator has been developed [2]. In simulations ASTRO uses MATLAB and NEURON environments [3] and is capable of representing various biologically relevant astroglial mechanisms such as calcium waves and diffusion. In this work we used ASTRO to simulate several astrocytic functions with the help of existing in vivo morphologies from various brain areas. We concentrated on calcium transients, as calcium-mediated signaling is thought to be the main mechanism of intra- and intercellular messaging between astroglia and other neural cell types. The time-scales of these calcium- mediated events have recently been shown to differ considerably in different spatial locations of astrocytes. We were able to reproduce these results in silico by simulating a morphologically detailed computational model that we developed based on previous work [4,5]. This was partly due to ASTRO’s capability to analyse the microscopic calcium dynamics in fine processes, branches and leaves.

With our model ASTRO proved to be a promising tool in simulating astrocytic functions and could potentially offer novel insights to glia-neuron interactions also in future work.

Acknowledgements: The work was supported by Academy of Finland through grants (297893, 326494, 326495) and the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2).

References:

1 Calì C, Agus M, Kare K, Boges DJ, Lehväslaiho H, Hadwiger M, Magistretti PJ. 3D cellular reconstruction of cortical glia and parenchymal morphometric analysis from Serial Block-Face Electron Microscopy of juvenile rat. Progress in Neurobiology 2019 Sep 21; 183: 101696.

2 Savtchenko LP, Bard L, Jensen TP, Reynolds JP, Kraev I, Medvedev N, Stewart MG, Henneberger C, Rusakov DA. Disentangling astroglial physiology with a realistic cell model in silico. Nature Communications 2018 Sep 3; 9(1), pp.1-15.

3 Carnevale T, Hines M. The NEURON Book. Cambridge University Press, Cambridge, UK; 2016.

4 Manninen T, Havela R, Linne M-L. Reproducibility and comparability of computational models for astrocyte calcium excitability. Frontiers in Neuroinformatics 2017 Feb 21;11:11.

5 Manninen T, Havela R, Linne M-L. Computational models for calcium-mediated astrocyte functions. Frontiers in Computational Neuroscience 2018 Apr 4;12:14.

Speakers
avatar for Ippa Seppala

Ippa Seppala

Medicine and Health Sciences, Tampere University



Sunday July 19, 2020 9:00pm - 10:00pm CEST
Slot 08