The objective of the proposed studies is to elucidate neuroanatomical and neurochemical correlates of neuroplasticity. For this purpose, the kindling paradigm of seizure elicitation will be used. Kindling presents a powerful model of neuronal plasticity and is characterized through a progressive increase in seizure susceptibility over time. This progressive development of kindling is thought to be caused by a fundamental reorganization of the underlying neuronal circuitry. Little information is available about the anatomical and neurochemical correlates of kindling. For the proposed studies, kindling will be induced from the entorhinal cortex and the analyses of data will focus on, but not be limited to, hippocampus/dentate and adjacent entorhinal and pyriform cortices. The first studies of this proposal are designed to provide a detailed anatomical and neurochemical description of the kindling activated neuronal system. They are designed 1) to determine and compare the extent of the kindling activated System and 2) to determine and compare the neurochemical, in particular the peptide, composition of the activated system at different stages of kindling development. Subsequent studies are designed to examine potential neuronal mechanisms which could contribute to a reorganization of the neuronal circuitry. Thus, these studies are designed 3) to determine if and when during the development of kindling, alterations in peptide synthesis occur, 4) to determine if glucocorticoid receptors are expressed in kindling activated neurons, and 5) to determine if the expression of glucocorticoid receptor mRNA changes during or following the development of kindling. Kindling activated neurons will be identified through the immunocytochemical identification of the c-fos expression, while in situ hybridization of oligonucleotides will be used to identify the peptide or receptor mRNAs. The two methods will be combined for double-label studies, identifying mRNAs in kindling activated, c-fos expressing neurons. Densitometry measurements and single cell analysis of the hybridization signal will be used for the quantification of potential alterations in mRNA expression. The results of these studies will provide detailed information about processes of neuroplasticity and will be of relevance for diseases which result in reorganization and/or loss of hippocampal neurons, such as epilepsy, and Alzheimer's disease, and will also have relevance for neuronal correlates of aging.
| Pretel, S; Applegate, C D; Piekut, D (1997) Apoptotic and necrotic cell death following kindling induced seizures. Acta Histochem 99:71-9 |
| Pretel, S; Applegate, C D; Piekut, D T (1996) The kindling-activated neuronal network: recruitment of somatostatin-synthesizing neurons. Brain Res Bull 41:237-47 |
| Pretel, S; Applegate, C D; Piekut, D T (1995) Seizure-induced activation of enkephalin- and somatostatin-synthesizing neurons. Peptides 16:951-7 |
