A biophysical model of neuronal dynamics during energy deprivation

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Abstract

Cerebral ischemia is a condition in which insufficient blood flow to the brain leads to metabolic stress. This can result in synaptic transmission failure, disturbances in ion homeostasis and eventually, cell swelling or cell death. Previous research has shown a tipping point beyond which return to physiological behaviour is impossible. We study neuronal dynamics during energy deprivation to identify the transition from reversible to irreversible damage, focusing on excitatory synaptic transmission.
We have constructed a biophysical model of a presynaptic neuron within a finite extracellular space calibrated with experimental data. To maintain ion homeostasis, the transmembrane ion fluxes are counteracted by ion transporters, such as the energy-dependent sodium-potassium ATPase (NKA). To model glutamate endocytosis and exocytosis, we combine calcium-dependent glutamate release and uptake by the excitatory amino acid transporter. To simulate energy deprivation, we deactivate the NKA. Using our model, we study the transition from physiological to pathological behaviour. Furthermore, we analyze the different recovery time scales for ion homeostasis and glutamate clearance.
Our model faithfully reproduces baseline physiological behaviour. During ischemia, ion homeostasis and glutamate clearance are disturbed, and cell swelling occurs due to imbalanced osmotic pressure. Upon restoring energy supply, the neuron returns to the physiological state or approaches an irreversible pathological state in which the neuron is not excitable anymore. Recovery of ion homeostasis and synaptic transmission are not simultaneous. The neuron may return to physiological levels while excitotoxicity remains. In conclusion, our model allows simulation of neuronal dynamics during ischemia and during recovery.
Original languageEnglish
Publication statusPublished - 8 Aug 2023
Event6th International BonnBrain3 Conference 2023
- Bonn, Germany
Duration: 7 Aug 20239 Aug 2023
Conference number: 6

Conference

Conference6th International BonnBrain3 Conference 2023
Country/TerritoryGermany
CityBonn
Period7/08/239/08/23

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