A 3Rs platform for glial research: From animal to human to in-silico models

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Passive non-neuronal brain cells called astrocytes have emerged as a critical yet grossly understudied part of brain machinery. Atrocytes take up released neurotransmitters, maintain ionic homeostasis of the extracellular space, and generate a variety of molecular signlas that regulate neural circuit activity. However, the emerging difference between animal and human astroglia in their morphology and physiology threatens the harm-benefit ratio of animal preparations in this important field of neuroscience and neurology. In this respect, realistic computational models of astroglia and astroglia-neuronal networks could provide hypothesis testing, mechanistic physiological insights, and an inter-species knowledge transfer that are unattainable in animal experiments. Exploring such models ought to minimise animal experimentation with no loss of knowledge, yet the methodology to create the corresponding modelling environment is only beginning to emerge. Thus, the present project aims to combine an experimental methodological approach, on the one hand, and open-access computer-simulation platforms, on the other, that would shift the weight of knowledge-based glial research from animals to human tissue preparations and realistic computational models. This will be achieved through the three objectives: (i) to establish working experimental protocols for up-to-date studies of human astroglia in organised brain tissue, making them a commonly accessible, viable alternative to animal brain tissue research strategies, (ii) to create an open-access computational platform that enables exploratory investigation of realistic biophysical models of astroglia, thus reducing similarly aimed experimental trials in animals, and (iii) to generate an experimental data library adaptable for the functional comparison of animal and human astroglia, thus providing a guidance on potentially implausible extrapolation of animal data to human brain astroglia.