Numerous studies have shown that selective damage of dentate hilar neurons is a consistent pathology in temporal lobe epilepsy, and that this selective cell loss may underlie the pathophysiology of the epileptic state. However, very little is known about the normal cellular organization and physiology of the hilar region of the fascia dentata. Therefore, the goal of the proposed experiments is to identify the cellular properties and circuitry of dentate hilar neurons in normal rats. Intracellular recording from hilar cells in rat hippocampal slices will be identified morphologically following intracellular dye injection to reveal the fundamental electrophysiological properties of the major cell types and describe them morphologically at the light microscopic level. The circuitry of these cells will be determined by identifying the following for each cell type: 1) synaptic responses to stimulation of different afferent inputs, 2) responses to application of putative neurotransmitters and their selective receptor antagonists, and 3) their synaptic connections based on simultaneous recording from pairs of synaptically connected cells. In addition to this fundamental analysis of normal structure and function, experiments have been designed to address the mechanisms underlying the selective vulnerability of hilar cells. Specifically, the following issues will be addressed: 1) whether NMDA and/or quisqualate/kainate excitatory amino acid receptor activation is critical to hilar neuron damage, and 2) whether preferential GABAergic innervation or particularly strong potassium currents contribute to the resistance of granule cells. Thus, these studies will identify the normal physiology and morphology of dentate hilar neurons as well as address mechanisms underlying selective vulnerability and resistance. The ultimate goal of this research is to understand the cellular mechanisms that determine normal dentate and hippocampal excitability and how selective hilar cell loss may be related to the altered physiology of the epileptic state.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS030831-03
Application #
2268802
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1992-07-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Helen Hayes Hospital
Department
Type
DUNS #
157119244
City
Menands
State
NY
Country
United States
Zip Code
12204