Speaker
Description
Astrocytic calcium responses under glutamate or ATP stimuli are highly heterogeneous, ranging from oscillatory dynamics to sustained plateau-like signals [1]. In the case of multi-peaks-type responses, experimental observations consistently report a delay preceding the onset of large amplitude cytosolic calcium oscillations (LAO). This delay is captured by a novel astrocyte model based on [2], which exhibits a phase of small amplitude oscillations (SAO) before the onset of LAOs. Our computational results demonstrate that the duration of the delay depends on the number of SAOs, which is strongly modulated by the calcium concentration in the endoplasmic reticulum (ER): ER overload prolongs the delay, whereas depletion shortens it. To explain this behaviour, we analyse the model using slow–fast and canard theories, revealing its geometric structure and the presence of a folded node. The latter explains the origin of SAOs and provides a mechanistic explanation for discussing the duration of the delay. Guided by this insight, we design an in silico experiment to reactivate SAOs by exploiting the identified folded node structure. Specifically, we suggest that the low-affinity calcium chelator TPEN could restore transient SAOs by elevating the ER calcium concentration following TPEN wash-out. Overall, this study illustrates how slow–fast and canard theories can uncover the origins of delayed calcium signalling in multi-peaks responses.
Bibliography
[1] Handy, Gregory, et al. «Mathematical investigation of IP3-dependent calcium dynamics in astrocytes». Journal of Computational Neuroscience, vol. 42, fasc. 3, giugno 2017, pp. 257–73, https://doi.org/10.1007/s10827-017-0640-1.
[2] Taheri, Marsa, et al. «Diversity of Evoked Astrocyte Ca2+ Dynamics Quantified through Experimental Measurements and Mathematical Modeling». Frontiers in Systems Neuroscience, vol. 11, ottobre 2017, https://doi.org/10.3389/fnsys.2017.00079.
