The major goals of the experiments proposed are to define the properties of hilar and basket neurons of the dentate gyrus, to examine the effects of acetylcholine on these cells, and to evaluate the properties of dentate granule cells in kainic-acid- lesioned animals. Hilar neurons are uniquely situated to control the output of dentate granule cells which relay cortical inputs into the hippocampus. Over 60% of these cells are GABAergic and serve along with basket cells to inhibit dentate granule cells. However, hilar neurons are destroyed by prolonged seizures and kainic acid seizures, thereby removing a key inhibitory circuit in the dentate. Moreover, loss of hilar neurons induces a maladaptive synaptogenesis in dentate granule cells which may contribute to further epileptogenesis. Outlined in this proposal are experiments to evaluate the basic electrophysiological properties of hilar and basket neurons, to identify single GABAergic hilar neurons by Lucifer Yellow-GAD immunocytochemistry and single basket cells by Lucifer Yellow. Another experiment will study the effects of acetylcholine on these cells and how their firing pattern may be controlled by it. A third experiment will evaluate for epileptogenic properties of dentate granule cells after aberrant reinnervation has been induced by treatment with kainic acid. Information gained concerning the basic properties of GABAergic inhibitory neurons, and loss of inhibition with maladaptive restructuring of neuronal connections is crucial in understanding hippocampal epileptogenesis.
| Wong, B Y; Prince, D A (1990) The lateral spread of ictal discharges in neocortical brain slices. Epilepsy Res 7:29-39 |
| Wong, B Y; Coulter, D A; Choi, D W et al. (1988) Dextrorphan and dextromethorphan, common antitussives, are antiepileptic and antagonize N-methyl-D-aspartate in brain slices. Neurosci Lett 85:261-6 |
