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.
Neuronal firing and neuron-to-neuron synaptic wiring are currently widely described as orchestrated by astrocytes—elaborately ramified glial cells tiling the cortical and hippocampal space into non-overlapping domains, each covering hundreds of individual dendrites and hundreds thousands synapses. A key component to astrocytic signaling is the dynamics of cytosolic Ca2+ which displays multiscale spatiotemporal patterns from short confined elemental Ca2+ events (puffs) to Ca2+ waves expanding through many cells. Here, we synthesize the current understanding of astrocyte morphology, coupling local synaptic activity to astrocytic Ca2+ in perisynaptic astrocytic processes and morphology-defined mechanisms of Ca2+ regulation in a distributed model. To this end, we build simplified realistic data-driven spatial network templates and compile model equations as defined by local cell morphology. The input to the model is spatially uncorrelated stochastic synaptic activity. The proposed modeling approach is validated by statistics of simulated Ca2+ transients at a single cell level. In multicellular templates we observe regular sequences of cell entrainment in Ca2+ waves, as a result of interplay between stochastic input and morphology variability between individual astrocytes. Our approach adds spatial dimension to the existing astrocyte models by employment of realistic morphology while retaining enough flexibility and scalability to be embedded in multiscale heterocellular models of neural tissue. We conclude that the proposed approach provides a useful description of neuron-driven Ca2+-activity in the astrocyte syncytium.
We introduce the temperature-dependent autocatalytic coefficient into the Merkin-Needham-Scott version of the Selkov system and consider the resulting equations as a model for temperature-controlled, self-sustained glycolytic oscillations in a closed reactor. It has been shown that this simple model reproduces key features observed in the experiments with temperature growth: (i) exponentially decreasing period of oscillations; (ii) reversal of relative duration leading and tail fronts. The applied model also reproduces the modulations of oscillations induced by the periodic temperature change.
We study the influence of periodic influx on a character of glycolytic oscillations within the forced Selkov system. We demonstrate that such a simple system demonstrates a rich variety of dynamical regimes (domains of entrainment of different order (Arnold tongues), quasiperiodic oscillations, and chaos), which can be qualitatively collated with the known experimental data. We determine detailed dynamical regimes exploring the map of Lyapunov characteristic exponents obtained in numerical simulations of the Selkov system with periodic influx. In addition, a special study of the chaotic regime and the scenario of its origin in this system was evaluated and discussed.
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