| There are three research projects contained in this doctoral thesis. The first two projects describe normal plasticity and pathological changes associated with epilepsy-like activity that can occur in brain circuits in the hippocampus. The last project describes electrophysiological recordings of a non-neuronal cell type used to study host-parasite interactions.;My first research project aimed to uncover contributions to synaptic plasticity in the hippocampus.;Hippocampal circuity is plastic, and its synapses undergo long-term potentiation (LTP). This is thought to be a mechanism of memory formation. Perforant path inputs to the dentate gyrus can be enhanced by LTP in hilar circuitry to modify the flow of information that is relayed to the CA3 region. This enhancement occurs when the excitatory/inhibitory balance shifts in a controlled manner to favor excitation due to the induction of LTP; however, if the inhibitory barrier is overcome in an uncontrolled manner, seizure-like activity can generalize through the hippocampus. My second project investigated epileptiform activity in the hippocampus.;Epileptogenesis was induced using various experimental conditions. Hyperactivity was distributed throughout the DG, CA3 and CA1 sub-regions of the hippocampus. A group II metabotropic glutamate receptor agonist (2S,2' R,3'R)-2-(2',3'-Dicarboxycyclopropyl) glycine (DCG-IV) reversed epileptiform activity and reduced response amplitudes to electrical stimulation. In a final set of experiments, seizure-like activity was studied in animals lacking a vesicle protein called synaptophysin. In these knock-out mice seizure activity was evoked with very low stimulus currents.;My last project revealed a functional H+ conductance in a cell line used to model host-parasite interactions of Schistosomiasis, a disease caused by parasitic worms that afflicts >250 million people. This work also showed that H+ channels are necessary for reactive oxygen species production, a defensive mechanism of the cells. An allergen or toxin-like peptide/protein mixture of unknown composition released by the parasite enhances current responses through H+ channels that is countered by Zn2+, a potent H+ channel blocker. In this project experiments identified the primary conductance, and then tested the effects of parasitic secretions on the H+ channels. The knowledge gained at the basic level in this study has provided insight into the mechanisms at work in schistosomiasis pathology. |
