Computational Models of Astrocytes and Astrocyte–Neuron Interactions: Characterization, Reproducibility, and Future Perspectives

Manninen, Tiina; Havela, Riikka; Linne, Marja-Leena

doi:10.1007/978-3-030-00817-8_16

Cited by 11 publications

(49 citation statements)

References 172 publications

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“…Some of the other computational astrocyte models that steered the field are the models by Nadkarni and Jung ( 2003 ), Bennett et al ( 2005 ), Volman et al ( 2007 ), De Pittà et al ( 2009a ), Postnov et al ( 2009 ), and Lallouette et al ( 2014 ). However, irreproducible science, as we have reported in our other studies, is a considerable problem also among the developers of the astrocyte models (Manninen et al, 2017 , 2018 ; Rougier et al, 2017 ). Several other review, opinion, and commentary articles have addressed the same issue as well (see e.g., Cannon et al, 2007 ; De Schutter, 2008 ; Nordlie et al, 2009 ; Crook et al, 2013 ; Topalidou et al, 2015 ; McDougal et al, 2016 ).…”

Section: Introductionmentioning

confidence: 65%

“…This increase in the number of models does not, however, solely reflect the vast amount of experimental data that is currently presented for astrocytes and for their roles in brain functions and the regulation of the neuronal system. Several focused reviews of computational astrocyte and neuron-astrocyte models have appeared during the last few years (see e.g., Jolivet et al, 2010 ; Mangia et al, 2011 ; De Pittà et al, 2012 ; Fellin et al, 2012 ; Min et al, 2012 ; Volman et al, 2012 ; Wade et al, 2013 ; Linne and Jalonen, 2014 ; Tewari and Parpura, 2014 ; De Pittà et al, 2016 ; Manninen et al, 2018 ); of which our study (Manninen et al, 2018 ) is the most comprehensive evaluation of more than 60 models published by the end of 2014. In the present study, we characterize in more detail the biophysical and biochemical components of astrocytes that were taken into account in the astrocyte and neuron-astrocyte interaction models published by the end of 2017.…”

Section: Methodsmentioning

confidence: 99%

“…Table 1 presents altogether 106 astrocyte models. As in our other study (Manninen et al, 2018 ), we here limited our evaluation of models to astrocytic signal transduction pathways that were defined using several characteristics. First, models were able to include pre- and postsynaptic neuron models as part of the whole models.…”

Section: Methodsmentioning

confidence: 99%

“…Several reviews of theoretical and computational models have already been presented (for a review, see e.g., Jolivet et al, 2010 ; Mangia et al, 2011 ; De Pittà et al, 2012 ; Fellin et al, 2012 ; Min et al, 2012 ; Volman et al, 2012 ; Wade et al, 2013 ; Linne and Jalonen, 2014 ; Tewari and Parpura, 2014 ; De Pittà et al, 2016 ; Manninen et al, 2018 ). We found out in our previous study (Manninen et al, 2018 ) that most astrocyte models are based on the models by De Young and Keizer ( 1992 ), Li and Rinzel ( 1994 ), and Höfer et al ( 2002 ), of which the model by Höfer et al ( 2002 ) is the only one built specifically to describe astrocytic functions and data obtained from astrocytes. Some of the other computational astrocyte models that steered the field are the models by Nadkarni and Jung ( 2003 ), Bennett et al ( 2005 ), Volman et al ( 2007 ), De Pittà et al ( 2009a ), Postnov et al ( 2009 ), and Lallouette et al ( 2014 ).…”

Section: Introductionmentioning

confidence: 99%

“…We first categorize the existing models based on whether they are describing astrocytes or neuron-astrocyte interactions. We have previously described some aspects of the astrocyte and neuron-astrocyte models in our related study (Manninen et al, 2018 ), where we listed the details of both the astrocyte and neuron models in a simplistic, educational manner. In this review, we characterize in detail the existing models based on what kind of astrocytic mechanisms have been taken into account.…”

Section: Introductionmentioning

confidence: 99%

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Computational Models for Calcium-Mediated Astrocyte Functions

Manninen

Havela

Linne

2018

Front. Comput. Neurosci.

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The computational neuroscience field has heavily concentrated on the modeling of neuronal functions, largely ignoring other brain cells, including one type of glial cell, the astrocytes. Despite the short history of modeling astrocytic functions, we were delighted about the hundreds of models developed so far to study the role of astrocytes, most often in calcium dynamics, synchronization, information transfer, and plasticity in vitro, but also in vascular events, hyperexcitability, and homeostasis. Our goal here is to present the state-of-the-art in computational modeling of astrocytes in order to facilitate better understanding of the functions and dynamics of astrocytes in the brain. Due to the large number of models, we concentrated on a hundred models that include biophysical descriptions for calcium signaling and dynamics in astrocytes. We categorized the models into four groups: single astrocyte models, astrocyte network models, neuron-astrocyte synapse models, and neuron-astrocyte network models to ease their use in future modeling projects. We characterized the models based on which earlier models were used for building the models and which type of biological entities were described in the astrocyte models. Features of the models were compared and contrasted so that similarities and differences were more readily apparent. We discovered that most of the models were basically generated from a small set of previously published models with small variations. However, neither citations to all the previous models with similar core structure nor explanations of what was built on top of the previous models were provided, which made it possible, in some cases, to have the same models published several times without an explicit intention to make new predictions about the roles of astrocytes in brain functions. Furthermore, only a few of the models are available online which makes it difficult to reproduce the simulation results and further develop the models. Thus, we would like to emphasize that only via reproducible research are we able to build better computational models for astrocytes, which truly advance science. Our study is the first to characterize in detail the biophysical and biochemical mechanisms that have been modeled for astrocytes.

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Section: Introductionmentioning

confidence: 65%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Computational Models for Calcium-Mediated Astrocyte Functions

Manninen

Havela

Linne

2018

Front. Comput. Neurosci.

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Neuron–Glia Interactions and Brain Circuits

Linne

Acimovic

Saudargienė

et al. 2022

Advances in Experimental Medicine and Biology

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Analysis of Network Models with Neuron-Astrocyte Interactions

2023

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Neural networks, composed of many neurons and governed by complex interactions between them, are a widely accepted formalism for modeling and exploring global dynamics and emergent properties in brain systems. In the past decades, experimental evidence of computationally relevant neuron-astrocyte interactions, as well as the astrocytic modulation of global neural dynamics, have accumulated. These findings motivated advances in computational glioscience and inspired several models integrating mechanisms of neuron-astrocyte interactions into the standard neural network formalism. These models were developed to study, for example, synchronization, information transfer, synaptic plasticity, and hyperexcitability, as well as classification tasks and hardware implementations. We here focus on network models of at least two neurons interacting bidirectionally with at least two astrocytes that include explicitly modeled astrocytic calcium dynamics. In this study, we analyze the evolution of these models and the biophysical, biochemical, cellular, and network mechanisms used to construct them. Based on our analysis, we propose how to systematically describe and categorize interaction schemes between cells in neuron-astrocyte networks. We additionally study the models in view of the existing experimental data and present future perspectives. Our analysis is an important first step towards understanding astrocytic contribution to brain functions. However, more advances are needed to collect comprehensive data about astrocyte morphology and physiology in vivo and to better integrate them in data-driven computational models. Broadening the discussion about theoretical approaches and expanding the computational tools is necessary to better understand astrocytes’ roles in brain functions.

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Computational Models of Astrocytes and Astrocyte–Neuron Interactions: Characterization, Reproducibility, and Future Perspectives

Cited by 11 publications

References 172 publications

Computational Models for Calcium-Mediated Astrocyte Functions

Computational Models for Calcium-Mediated Astrocyte Functions

Neuron–Glia Interactions and Brain Circuits

Analysis of Network Models with Neuron-Astrocyte Interactions

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