The mechanisms underlying the transition to seizure are still unresolved. Proposed mechanisms include excitatory GABAergic drive, loss of interneuron-mediated inhibition, and glutamatergic input potentiation. The objective of this thesis was to investigate the relative contributions of synchronized glutamatergic and GABAergic inputs and their functional roles during ictogenesis in the epileptic neonatal (postnatal days 6-12) mouse hippocampus, induced with 0.25mM Mg2+/5mM K+ perfusion. Simultaneous field and whole-cell patch-clamp recordings were obtained from CA3 stratum-oriens interneurons and pyramidal cells.
The antagonists for GABAA and glutamate receptors abolished the preictal and ictal discharges, respectively, suggesting that the preictal state is mediated by the coherent discharges of GABAergic inhibitory interneurons, whereas the recurrent excitatory inputs are required for ictogenesis. Synaptic charge transfers underlying the synchronized discharges showed a dynamic change in the balance between the inputs: GABAergic currents markedly diminished by ictal onset whereas glutamatergic currents dominated at ictal onset and throughout the ictus.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/30134 |
| Date | 30 November 2011 |
| Creators | Zhang, Zhang Jane |
| Contributors | Carlen, Peter Louis |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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