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Title: A biophysical model of the role of astrocytes in hyper-excitability
Author: Flanagan, Bronac
ISNI:       0000 0004 8504 1943
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2019
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The human brain consists of numerous networks of cells, working in harmony to operate one of the most intricate structures in existence. A fine balance between excitation and inhibition of neurons is necessary to operate functionally, a task attributed to the brain cell type, astrocytes. This thesis investigates the astrocytic mechanisms controlling the balance of excitatory neurotransmitter, glutamate, and inhibitory neurotransmitter, GABA, at the synapse between neurons, to propose a new hypothesis: that an elevated astrocytic glutamate content is sufficient to disturb the balance between excitation and inhibition at the glutamatergic synapse. To test this hypothesis, the astrocytic transport mechanisms within the tripartite synapse are reviewed both from a biological and computational perspective. A new computational model was developed to highlight the implications of an elevated astrocytic glutamate level for synaptic clearance of excitatory neurotransmitter and resulting hyperexcitability of the adjacent neuron. Furthermore the coupling of astrocytic glutamate clearance with inhibitory GABA release is demonstrated. This thesis highlights one method of astrocytic-mediated neuronal modulation, which is sensitive to fluctuations in ionic changes and thus elevated astrocytic glutamate content.
Supervisor: Wong-Lin, Kongfatt ; McDaid, Liam ; Harkin, Jim Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Glutamate ; GABA ; Computational model