Sodium–Calcium Exchanger Can Account for Regenerative Ca2+ Entry in Thin Astrocyte Processes

Calcium transients in thin astrocytic processes can be important in synaptic plasticity, but their mechanism is not completely understood. Clearance of synaptic glutamate leads to increase in astrocytic sodium. This can electrochemically favor the reverse mode of the Na/Ca-exchanger (NCX) and allow calcium into the cell, accounting for activity-dependent calcium transients in perisynaptic astrocytic processes. However, cytosolic sodium and calcium are also allosteric regulators of the NCX, thus adding kinetic constraints on the NCX-mediated fluxes and providing for complexity of the system dynamics. Our modeling indicates that the calcium-dependent activation and also calcium-dependent escape from the sodium-mediated inactive state of the NCX in astrocytes can form a positive feedback loop and lead to regenerative calcium influx. This can result in sodium-dependent amplification of calcium transients from nearby locations or other membrane mechanisms. Prolonged conditions of elevated sodium, for example in ischemia, can also lead to bistability in cytosolic calcium levels, where a delayed transition to the high-calcium state can be triggered by a short calcium transient. These theoretical predictions call for a dedicated experimental estimation of the kinetic parameters of the astrocytic Na/Ca-exchanger

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Isolated wave segments in a neural tissue model with volume transmission: discreteness matters

Isolated wave segments are a type of spatiotemporal activity that has been repeatedly reported in experimental studies of spreading depolarization on the cerebral cortex and retina of laboratory animals. However, it has been theoretically shown that such a pattern cannot be stable in a continuous excitable medium. In our work, we address this problem using the model of a discrete–continuous medium. We present the targeted numerical study of isolated wave segments, including scenarios of their emergence and an estimation of their stability to various deformations. We show that an isolated wave segment can exhibit the properties of a space-time attractor by cyclically changing its shape and approaching it from different initial conditions. Such a wave segment is not necessarily small, although small segments may occur more easily and are, therefore, more likely. Finally, we show that the behavior we found persists also under conditions of a heterogeneous propagation medium, which indicates the applicability of our findings to the analysis of spatiotemporal patterns in real nervous tissue