A computational model of altered neuronal activity in altered gravity

Abstract

AbstractElectrophysiological experiments have shown that neuronal activity changes upon exposure to altered gravity. More specifically, the firing rate increases during microgravity and decreases during centrifugal-induced hypergravity. However, the mechanism by which altered gravity impacts neuronal activity is still unknown. Different explanations have been proposed: a first hypothesis states that microgravity increases the fluidity of the cell membrane and modifies the properties of the neurons’ ion channels. Another hypothesis suggests the role of mechano-gated (MG) ion channels depolarizing the cells during microgravity exposure. Although intuitive, these models have not been backed by quantitative analyses nor simulations. Here, we developed computational models of the impact of altered gravity, both on single cell activity and on population dynamics. Firstly, in line with previous electrophysiological experiments, we suggest that microgravity could be modelled as an increase of the voltage-dependent channel transition rates, which are assumed to be the result of higher membrane fluidity and can be readily implemented into the Hodgkin-Huxley model. Using in-silico simulations of single neurons, we show that this model of the influence of gravity on neuronal activity allows to reproduce the increased firing and burst rates observed in microgravity. Secondly, we explore the role of MG ion channels on population activity. We show that recordings can be fitted by a network of connected excitatory neurons, whose activity is balanced by firing rate adaptation. Adding a small depolarizing current to account for the activation of mechano-gated channels also reproduces the observed increased firing and burst rates. Overall, our results fill an important gap in the literature, by providing a computational link between altered gravity and neuronal activity.