University of Twente Student Theses


Modelling of spontaneous glutamate plumes

Alphen, Fleur van (2023) Modelling of spontaneous glutamate plumes.

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Embargo date:2 May 2025
Abstract:Introduction: In pathological conditions, glutamate release can show abnormal dynamic behaviour, characterized by plumes: a relatively large and fast increase in extracellular glutamate concentration, followed by a slow removal. Glutamate plumes appear to result from impaired astrocyte clearance of synaptically released glutamate. Although experiments with TTX show that plumes are independent of neuronal action potentials, the spontaneous activation of presynaptic voltage-gated calcium channels seems to be the source of the plumes. OBJECTIVE: We aim to understand critical determinants of glutamate plume generation and clearance in silicon. Methods: We use an existing computational model of the tripartite synapse (Kalia PLoS Comput Biol. 2021) that includes extensive neuronal glutamate dynamics and energy-dependent dynamics. We aim to generate glutamate plumes in relation to ischemic stress, blocked channels, and as a response to various ion injections. We corrected several inconsistencies in the implementation, including the voltage-gated calcium current. We also analyze a flaw during the glutamate release that causes an implausible glutamate dip in the extracellular space before glutamate is released. Results: Our simulations indicate that energy deprivation may cause calcium-dependent synaptic glutamate release, independent of action potentials, but this glutamate release does not resemble glutamate plumes. We show that increased neuronal calcium concentrations alone are unlikely to cause noteworthy glutamate release, but calcium increase during a temporal astrocytic EAAT block can result in plume-like glutamate release. Furthermore, we show that even without neuronal glutamate release, a temporal astrocytic EAAT impairment can result in a plume-like extracellular glutamate transient. Conclusion: Our research supports the hypothesis that a combination of impaired astrocytic EAAT and an increase in neuronal calcium can lead to glutamate plumes. We also propose that stochastic temporal astrocytic EAAT blocks could lead to glutamate plumes.
Item Type:Essay (Master)
Faculty:EEMCS: Electrical Engineering, Mathematics and Computer Science
Subject:31 mathematics, 44 medicine
Programme:Applied Mathematics MSc (60348)
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