Challenges in Reproducibility, Replicability, and Comparability of Computational Models and Tools for Neuronal and Glial Networks, Cells, and Subcellular Structures.

The possibility to replicate and reproduce published research results is one of the biggest challenges in all areas of science. In computational neuroscience, there are thousands of models available. However, it is rarely possible to reimplement the models based on the information in the original publication, let alone rerun the models just because the model implementations have not been made publicly available. We evaluate and discuss the comparability of a versatile choice of simulation tools: tools for biochemical reactions and spiking neuronal networks, and relatively new tools for growth in cell cultures. The replicability and reproducibility issues are considered for computational models that are equally diverse, including the models for intracellular signal transduction of neurons and glial cells, in addition to single glial cells, neuron-glia interactions, and selected examples of spiking neuronal networks. We also address the comparability of the simulation results with one another to comprehend if the studied models can be used to answer similar research questions. In addition to presenting the challenges in reproducibility and replicability of published results in computational neuroscience, we highlight the need for developing recommendations and good practices for publishing simulation tools and computational models. Model validation and flexible model description must be an integral part of the tool used to simulate and develop computational models. Constant improvement on experimental techniques and recording protocols leads to increasing knowledge about the biophysical mechanisms in neural systems. This poses new challenges for computational neuroscience: extended or completely new computational methods and models may be required. Careful evaluation and categorization of the existing models and tools provide a foundation for these future needs, for constructing multiscale models or extending the models to incorporate additional or more detailed biophysical mechanisms. Improving the quality of publications in computational neuroscience, enabling progressive building of advanced computational models and tools, can be achieved only through adopting publishing standards which underline replicability and reproducibility of research results.

Computational Models for Calcium-Mediated Astrocyte Functions.

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.

Reproducibility and Comparability of Computational Models for Astrocyte Calcium Excitability.

The scientific community across all disciplines faces the same challenges of ensuring accessibility, reproducibility, and efficient comparability of scientific results. Computational neuroscience is a rapidly developing field, where reproducibility and comparability of research results have gained increasing interest over the past years. As the number of computational models of brain functions is increasing, we chose to address reproducibility using four previously published computational models of astrocyte excitability as an example. Although not conventionally taken into account when modeling neuronal systems, astrocytes have been shown to take part in a variety of in vitro and in vivo phenomena including synaptic transmission. Two of the selected astrocyte models describe spontaneous calcium excitability, and the other two neurotransmitter-evoked calcium excitability. We specifically addressed how well the original simulation results can be reproduced with a reimplementation of the models. Additionally, we studied how well the selected models can be reused and whether they are comparable in other stimulation conditions and research settings. Unexpectedly, we found out that three of the model publications did not give all the necessary information required to reimplement the models. In addition, we were able to reproduce the original results of only one of the models completely based on the information given in the original publications and in the errata. We actually found errors in the equations provided by two of the model publications; after modifying the equations accordingly, the original results were reproduced more accurately. Even though the selected models were developed to describe the same biological event, namely astrocyte calcium excitability, the models behaved quite differently compared to one another. Our findings on a specific set of published astrocyte models stress the importance of proper validation of the models against experimental wet-lab data from astrocytes as well as the careful review process of models. A variety of aspects of model development could be improved, including the presentation of models in publications and databases. Specifically, all necessary mathematical equations, as well as parameter values, initial values of variables, and stimuli used should be given precisely for successful reproduction of scientific results.