Excitotoxic events in the brain have many causes and can lead to neuron death and impaired cognitive abilities. This proposal is designed to assess the ability of gene therapy techniques, that increase neuron survival following insult, to maintain normal physiology in an animal model of epilepsy. I will perform in vivo electrophysiology with microperfusion to record changes in evoked synaptic responses following injection of Kainic acid and protective viral vectors. These experiments will be the first to characterize the effects of in vivo kainic acid microinjection on hippocampal synaptic transmission measured 72 hr after injection. As well, this study marks the initiation of research into the ability of the glut-1 and the Bcl-2 vectors to pare neuronal function following excitotoxic insult. Furthermore, results form these experiments will aid in the development of therapeutic treatments for synaptic malfunction of various sorts. The molecular biology techniques acquired while carrying out this proposal will allow for future study of neurophysiological changes that occur during learning, aging and disease.
| Dumas, T C; Powers, E C; Tarapore, P E et al. (2004) Overexpression of calbindin D(28k) in dentate gyrus granule cells alters mossy fiber presynaptic function and impairs hippocampal-dependent memory. Hippocampus 14:701-9 |
| Dumas, T C; McLaughlin, J R; Ho, D Y et al. (2000) Gene therapies that enhance hippocampal neuron survival after an excitotoxic insult are not equivalent in their ability to maintain synaptic transmission. Exp Neurol 166:180-9 |
