Computational Model of Noradrenaline Modulation of Astrocyte Responses to Synaptic Activity

Andrey Verisokin, Darya Verveyko, Artem Kirsanov, Alexey Brazhe and Dmitry Postnov ()
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Andrey Verisokin: Department of Theoretical Physics, Kursk State University, Radishcheva St. 33, 305000 Kursk, Russia
Darya Verveyko: Department of Theoretical Physics, Kursk State University, Radishcheva St. 33, 305000 Kursk, Russia
Artem Kirsanov: Department of Biophysics, Biological Faculty, Lomonosov Moscow State University, Leninskie Gory St. 1/24, 119234 Moscow, Russia
Alexey Brazhe: Department of Biophysics, Biological Faculty, Lomonosov Moscow State University, Leninskie Gory St. 1/24, 119234 Moscow, Russia
Dmitry Postnov: Department of Optics and Biophotonics, Saratov State University, Astrakhanskaya St. 83, 410012 Saratov, Russia

Mathematics, 2023, vol. 11, issue 3, 1-20

Abstract: The mathematical modeling of synaptically connected neuronal networks is an established instrument for gaining insights into dynamics of neuronal ensembles and information processing in the nervous system. Recently, calcium signaling in astrocytes—glial cells controlling local tissue metabolism and synapse homeostasis—and its corresponding downstream effect on synaptic plasticity and neuromodulation appeared in the limelight of modeling studies. Here, we used mechanism-based mathematical modeling to disentangle signaling pathways and feedback loops in the astrocytic calcium response to noradrenaline, an important neuromodulator marking periods of heightened alertness and arousal. The proposed model is based on an experiment-based 2D representation of astrocyte morphology, discrete random glutamate synapses with placement probability defined by the morphology pattern, and spatially heterogeneous noradrenaline sources, reflecting axonal varicosities of the adrenergic axons. Both glutamate and noradrenaline drive Ca 2 + dynamics in the astrocyte in an additive or synergistic manner. Our simulations replicate the global activation of astrocytes by noradrenaline and predict the generation of high-frequency Ca 2 + waves in a dose-dependent manner and the preferred Ca 2 + wave origination near noradrenaline release sites if they colocalise with high-density clusters of glutamate synapses. We tested positive feedback loops between noradrenaline release and glutamate spillover directly or mediated by gliotransmitter release from the activated astrocyte. The simulations suggest that the coupled stochastic drive by glutamate and noradrenaline release converges on the graded modulation of the IP 3 level, which is translated into whole-cell Ca 2 + waves of different frequencies. Thus, the proposed approach is supported by experimental data and can be used to address situations inaccessible directly by experiment, and is a starting point for a more detailed model that includes other signaling mechanisms providing negative feedback.

Keywords: astrocytes; norepinephrine; noradrenaline; glutamate; synapses; calcium dynamics; neuron; modeling (search for similar items in EconPapers)
JEL-codes: C (search for similar items in EconPapers)
Date: 2023
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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