The aims are to provide a more detailed description of the role of excitatory amino acids in normal and disordered neuronal functioning. They are intended to expand our understanding of the way different excitatory amino acid receptors influence neuronal activity and provide insights into how transmitter metabolism affects synaptic release. Studies relating anoxic neuronal death to accumulation of excitatory amino acids will have direct clinical relevance to stroke and perinatal brain injury. Specific goals include: 1. a. Localizing receptors for N-methyl-aspartate (NMDA) and kainate (KA). b. Determining the role of the NMDA receptor in regulating synaptic activity. c. Determining conditions for NMDA receptor activation. d. Determining whether NMDA influences voltage dependent conductances. e. Determining whether presynaptic KA or aminophosphonobutyrate receptors exist. 2. Characterizing long term potentiation in tissue culture and defining factors which control expression of amino acid receptors in vitro. 3. Studying the effect of altered extracellular glutamine on spontaneous and evoked synaptic activity. 4. a. Trying to protect neurons from anoxia by removing chloride from the extracellular space. b. Investigating the mechanisms of late, excitotoxic neuronal death. c. Determining whether histochemical analysis of ATP will be a useful marker in anoxic brain slices. d. Determining whether synaptic release of excitatory amino acids is responsible for the death of rodent neocortical neurons in vitro. e. Determining whether excitatory amino acids mediate the death of human neocortical neurons in vitro. f. Trying to produce delayed, anoxic death in hippocampal and cortex cultures and determining whether it can be prevented by amino acid antagonists.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019988-04
Application #
3400136
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1983-09-10
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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