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.
- Computational model
A Biophysical Model of the Role of Astrocytes in Hyper-Excitability
Flanagan, B. (Author). Oct 2019
Student thesis: Doctoral Thesis