CNS* 2019 Workshop, Barcelona, 16th of July, 2019
W21 – Modeling astrocyte functions:
From ion channels to calcium dynamics and beyond
Home page: https://sites.tuni.fi/cns2019-w21astro/
Overview
A fundamental question in neuroscience is how different mechanisms of glial cell function, particularly the astrocytes, are linked with cognitive functions and behavior in mammals, as well as in mechanisms of brain disease. Various evidence has accumulated on the roles of astrocytes in neuronal excitability, synaptic transmission, plasticity, and in higher cognitive functions. It is a disturbing reality that most of computational cellular neuroscience concentrates on modeling of the neuronal functions only, largely ignoring other brain cells in the models of neural circuits. Their roles in electrical, neuromodulatory and metabolic signaling is being elucidated daily, and their quantitative properties slowly emerge. The goal of the workshop is to present the state-of-the-art in quantitative aspects of astrocytic function and computational modeling of astrocytes in order to facilitate better understanding of the functions and dynamics of brain circuits. We concentrate on single astrocyte and small astrocyte networks, with an emphasis on methodological issues and principal difficulties for bridging the gap between the models and experimental studies.
Organizers
Marja-Leena Linne, Tampere University, Faculty of Medicine and Health Technology, Finland, marja-leena.linne@tuni.fi
Predrag Janjic, Macedonian Academy of Sciences and Arts (MANU), Skopje, North Macedonia, predrag.a.janjic@gmail.com
Workshop schedule: July 16th 2019, from 9:30h – 13:10h, venue to be decided
Registration information: All workshop participants need to register on CNS*2019 conference. Please visit registration pages.
Workshop program
9:30 – 9:40 Short introduction by the organizers (5-10 min):
Why is glioscience modeling neglected within the field of computational neuroscience?
– Where we would introduce the workshop and try to motivate an active participation
9:40-10:00 Marja-Leena Linne, Tampere University, Finland, marja-leena.linne@tuni.fi
Understanding the role of glial cells in brain functions through in vivo, in vitro and in silico approaches
In this talk, I will give a short introduction to astroglial cells. I will additionally discuss the partially controversial roles of astroglial cells in brain functions in health and disease. To solve the controversies a variety of modeling approaches, tools and roadmaps have been recently introduced. The good, well-validated models, however, remain scarce. I will highlight the previous work on modeling astrocytic calcium dynamics both in single cells and in in vitro networks as well as discuss the strengths and weaknesses of the models from the biological perspective.
10:00 – 10:25 Corrado Cali, King Abdullah University of Science and Technology, Saudi Arabia, corrado.cali@gmail.com
Morphological basis of brain energy metabolism in the mammalian brain: focus on astrocytes
Growing evidence suggests that the key to unveil mammalian brain’s computational efficiency represent relies in its complex energy management system. 3D reconstructions from serial electron microscopy can be used to analyze the morphological relationship between neurons, glia and vasculature. Finally, by inferring the distribution of glycogen, a major source of energy, within astrocytes, it is possible to voxelize the space and implement simulations using equations governing the astrocyte-neuron lactate shuttle (ANLS) with spatio-temporal accuracy.
10:25-10:50 Tiina Manninen, Tampere University, Finland & Stanford University, USA, tiina.manninen@tuni.fi
Computational models of astrocyte calcium dynamics and astrocyte-neuron interactions
In silico studies are one way to help solve the challenges and controversies related to neuron-astrocyte interactions. Hundreds of models exist for describing some specific astrocytic phenomena but astrocytic modeling is not as advanced as neuronal modeling. In this presentation, I will show our results on categorization of a hundred computational models of astrocytes and neuron-astrocyte interactions. I will also address were we able to reproduce the original simulation results by implemented a model ourselves based on the information in the original article.
Coffee break (20 min)
11:20 – 11:45 Predrag Janjic Macedonian Academy of Sciences and Arts, North Macedonia, predrag.a.janjic@gmail.com
Quantitative description of potassium transport in astrocytes – Are the dynamical models in reach?
Even though astrocytic membrane is not excitable, it is endowed with a great variability of ion transport mechanisms, which is likely reason why the experiments and quantitative models still can’t resolve the controversies of their differential roles in ion homeostasis. I will talk on the quantitative description of complex potassium Kir and K2P pores in astrocytes addressing the specificity of dynamical models which include ion concentration dynamics, coupling and specific nature of perturbations. Looking beyond the brain, common substrates of potassium homeostasis in other systems, suggest possible generic model of potassium homeostasis.
11:45 – 12:10 Leonid Savtchenko, UCL London, UK
ASTRO: A Cloud-computing model builder to explore realistically morphed astrocytes in-silico, skaalsa@live.ucl.ac.uk
To resolve the challenges of compartmental modelling and computations of astrocyte with complex geometry, we propose the model builder ASTRO. The platform enables in-silico reconstruction of nanoscopic 3D cell morphology and incorporation of known signaling mechanisms. ASTRO is based on NEURON and engages remote cloud computing. ASTRO can evaluate key electrogenic features of the cell membrane, basic aspects of spatiotemporal intracellular K+ and Ca2+ dynamics including multi-component Ca2+ buffering, against multi-disciplinary experimental data obtained in astroglia.
12:10 – 12:35 Gaute Einevoll, University of Oslo, Norway, gaute.einevoll@nmbu.no
Modeling astrocytic regulation of extracellular ion concentrations and extracellular fields
Astrocytes share extracellular space (ECS) with neurons and may thus indirectly modify neuronal dynamics by uptake and release of ions through their cell membranes. An example is the spatial buffering of local excess of potassium from ECS, transported away through astrocytes to prevent pathological spiking. An understanding of this process is of clinical relevance, as several pathological conditions, such as spreading depression, migraine and epilepsy, are associated with increased extracellular potassium concentrations, which in turn typically coincide with a DC-like drop in the local extracellular potential. In the seminar the recently introduced Kirchhoff-Nernst-Planck (KNP) scheme for modelling such ion dynamics in brain tissue (neurons, astrocytes, ECS) will be described. Further, the putative measurement of such ion dynamics by extracellular electrodes, in particular by recording the local field potential (LFP), will be discussed.
12:40 – 13:10 Discussion and Wrap-up.