Astrocytes are the second most abundant cell type in the human brain. Recent experimental data show that they can interact with neurons and can modulate neuronal activity. Those interactions occur at fine astrocytic ramifications called processes. In response to neuronal activity, astrocyte processes exhibit intracellular calcium signals. However, it is not clear how these signals are transmitted to and integrated in the astrocyte and how it is propagated to other parts of the astrocyte or to other cells. The localization of the main molecular actors in the processes, as well as the geometry of the system are essential for understanding calcium signal integration and propagation. However, most of those data still resist experimental quantification because of the small sizes and volumes concerned. Modeling is the only approach that can investigate those questions.
The goal of my PhD is to develop a biologically-realistic kinetic Monte-Carlo model (agent-based model) and use it to simulate calcium signaling in fine astrocytic processes. First, I will investigate calcium signal generation in the system. Then, signal integration and propagation in the subcellular network-forming process will be explored.