The broad goal of this project is to identify and analyze alterations in the neurochemical anatomy of humans and animal models with seizure disorders. Three groups of studies will be included. The first group will focus on the localization of GABA receptors in human and rat control and epileptic tissue since regional differences in the location of the subtypes could have important implications for the basic mechanisms and treatment of seizure disorders. Emphasis will be placed on localization in the hippocampal formation and cerebral cortex. Three methods will be used to provide a comprehensive view of GABA receptor subtype distribution: 1) in situ hybridization to identify neurons that synthesize the different receptor proteins; 2) immunocytochemistry to describe the specific cellular localization of the receptor subtypes; and 3) autoradiography to identify binding patterns of GABA receptor ligands that are similar to those of GABA receptor subtypes. The second group of studies will expand descriptions of morphological reorganization of neurons in the hippocampus of patients with temporal lobe epilepsy (TLE) by ultrastructural analysis of these changes; in situ hybridization studies of prodynorphin mRNA in control and TLE specimens; and descriptions of the circuitry of remaining hippocampal neurons in TLE. The third series of studies will utilize an animal model to determine the types of neurochemical and morphological changes that precede and may underlie increased seizure susceptibility. A rat model of febrile seizures has been selected because febrile convulsions are a common finding in the history of patients with temporal lobe epilepsy.
One specific aim i s to test the hypothesis that mossy fiber reorganization occurs following hyperthermic seizures during the first two postnatal weeks in the rat.
| Esclapez, M; Chang, D K; Houser, C R (1996) Subpopulations of GABA neurons in the dentate gyrus express high levels of the alpha 1 subunit of the GABAA receptor. Hippocampus 6:225-38 |
| Esclapez, M; Tillakaratne, N J; Kaufman, D L et al. (1994) Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms. J Neurosci 14:1834-55 |
| Houser, C R; Esclapez, M (1994) Localization of mRNAs encoding two forms of glutamic acid decarboxylase in the rat hippocampal formation. Hippocampus 4:530-45 |
| Esclapez, M; Tillakaratne, N J; Tobin, A J et al. (1993) Comparative localization of mRNAs encoding two forms of glutamic acid decarboxylase with nonradioactive in situ hybridization methods. J Comp Neurol 331:339-62 |
