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1) The structure and function of the mammalian hippocampal formation with specific reference to its involvement in the development of epilepsy and other neurological disorders;
2) Understanding the mechanisms that initiate neuronal death, and how the loss of particular neuronal populations may alter network structure and fucntion;
3) The identification of new pharmacological approches for the treatment of epilepsy.
We utilize a wide variety of investigative electrophysiological and neuroanatomical methods to confirm experimentally induced structural changes induced by seizure activity or the injection of neurotoxic agents, including evoked potential recording in anesthetized and awake animals, histological methods for the localization of proteins and amino acid neurotransmitters, silver staining for the detection of degenerating cells, in situ hybridization for the cellular localization of mRNA, and electron microscopy.
First demonstration that focal seizure activity produced by electrical stimulation causes irreversible brain damage (1981)
First identification of the brain cells most vulnerable to seizures activity (1987)
Discovery that adrenalectomy causes selective and total degeneration of hippocampal granule cells by apoptosis (1989)
Formulation of the “dormant basket cell hypothesis” as an explanation for the epileptic hyperexcitability caused by injury-induced neuronal pathology (1991)
First demonstration that mossy fiber “sprouting” (injury-induced synaptic reorganization) is inhibitory rather than epileptogenic (1992)
First demonstration of physiological lateral inhibition in the rat dentate gyrus (1995)
First demonstration that excitatory dentate granule cells normally express GAD67 and GABA, as well as glutamate, and that experimental seizures increase granule cell GAD and GABA concentrations 6 fold; this is the first unequivocal example that some brain cells normally contain two small amino acid transmitters, one excitatory and one inhibitory (1996)
First use of Stable Substance P-saporin conjugate as a method for selectively destroying hippocampal inhibitory interneurons (2001)
Demonstration of commissurally-projecting inhibitory interneurons in the rat hippocampus (2001)
Discovery of “tectonic” hippocampal malformations in human temporal epilepsy (2003)
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