Franziska Oschmann: Computational modelling of glutamate-induced calcium signal generation and propagation in astrocytes

BCCN Berlin / GRK 1589 / TU Berlin

Since the 1990s researchers have shown that astrocytes generate calcium oscillations in response to neuronal activity and propagate them as intercellular calcium waves over long distances. Moreover, astrocytes release transmitters in a calcium-dependent manner and by that signal to neurons. These discoveries have made astrocytes and especially calcium signal generation and propagation in astrocytes an important research area in the neuroscience field. However, although the impact of astrocytes at single synapses is well understood, the functional role of astrocytes in neuronal networks is not captured yet. Therefore, it is of high importance to fully understand the generation and propagation of calcium signals, in order to predict the behaviour of neuron-astrocyte networks. Coupled with that, the development of computational models has become an important method in the analysis and prediction of astrocytic calcium dynamics.
In the first part of my thesis, I develop a computational model reproducing the calcium signal generation at different positions along a subcellular compartment of the astrocyte, the astrocytic process. The novelty of my approach is the consideration of two interacting mechanisms for the generation of astrocytic calcium signals, namely the calcium entry from the extracellular space and the calcium release from internal stores. In addition, I apply parameters defining the astrocyte morphology in order to predict the calcium signal generation at different positions across the astrocyte. With this model I show that 1) seemingly there is a spatial separation of these two calcium signal generation mechanisms across the astrocyte, and 2) a high activity of both mechanisms evokes a depletion of the internal calcium store and the suppression of intracellular calcium oscillations.
In the second part of my thesis, I develop a reduced model for calcium signal generation in astrocytes and perform a stability analysis of this reduced model. The model reduction is based on the separation of time-scales of the dynamical variables and the subsequent derivation and application of the time-independent solutions of the fast-reacting variables. The stability analysis of the reduced system revealed that 1) the fixed-points of all dynamical variables are independent of those two parameters determining the impact of either the calcium release from internal stores or the calcium entry from the extracellular space and are solely determined by the extracellular stimulation, 2) the stabilities of all fixed points, however, are determined by these two parameters, and 3) the eigenvalues of the fixed points predict that the in part 1 observed depletion of internal calcium stores can be prevented by
an increased transport of calcium into internal stores.

Additional Information

PhD defense in the research training group GRK 1589, "Sensory Computation in Neural Systems".

Organized by

Klaus Obermayer / Robert Martin