Excitotoxicity is a phenomenon of the central nervous system in which prolonged electrical activity results in the death of nerve cells in specific parts of the brain. While often associated with diseases like epilepsy, this process can be induced in normal brains by applying naturally occurring neurotransmitters such as glutamic acid (glutamate). Several related glutamate-like molecules are known to be excitotoxic and they each interact with a different subset of glutamate receptors on the surface of nerve cells. Animal studies have revealed that excitotoxic susceptibility is an inherited trait in certain inbred laboratory mice. Injection of kainic acid, a potent excitotoxic glutamate-like molecule, induced seizures C57BL/6 (B6) and FVB/N (FVB) mice. However no nerve cells were lost in the brains of the B6 mice while the FVB mice show extensive nerve cell death. In preliminary experiments a hypothesis was tested: Is the mouse strain-specific difference in excitotoxin cell death the result of an intrinsic resistance in the B6 mouse nerve cells? Using glutamate to induce excitotoxicity the resistance of cultured B6 nerve cells was compared with cultured FVB nerve cells. The FVB neurons exhibited cell death and B6 neurons showed resistance to excitotoxicity. These results demonstrated that strain specific excitotoxic resistance in the B6 mice was a property of the nerve cells alone and not dependent on the environment of the living adult mouse brain. These data also showed that the strain difference in excitotoxic resistance seen in the live animal is present very early in neonatal development. This proposal will examine the differences between the B6 and FVB nerve cells in culture in order to determine what could account this difference in resistance. Finding the properties of the B6 nerve cells which confer resistance will enhance our understanding of excitotoxicity, whose role in brain function and dysfunction remains poorly understood.
Broader impact: CSU Chico is a comprehensive university with limited but growing research infrastructure. The department of Biological Sciences has made a commitment to undergraduate research by reducing teaching loads for active faculty, upgrading the research environment, and hiring faculty with established research backgrounds. This laboratory has been successful in producing Ph.D. graduate students, peer reviewed publications, and funded grants. This project will ensure continued and future student participation at meetings of professional societies, such as the Society for Neuroscience. These kinds of interactions are extremely valuable to students interested in pursuing research careers. This is an explicit goal of this institution and there is an impressive track record to support this effort. The one way to maintain this productivity is through active collaboration with colleagues at major Ph.D. granting universities; this project is a part of that effort. Other benefits include opportunities for colleagues at larger institutions to recruit able graduate students from this institution. These students will be some of society's future scientists. Finally, CSU Chico serves a large rural area of northern California, and funnels students from several regional community colleges to Bachelors and Masters level degrees.
