As our understanding of the nervous system increases, the questions posed by neuroscientists become more complex and require more sophisticated analytical schemes to answer them. A major challenge of contemporary neurobiology is to understand the cellular mechanisms responsible for neurotransmitter targeting and release. Essential to an understanding of neurotransmitter release is quantitative knowledge of the amounts and locations of neuropeptides present in the neuron. The methods currently employed for the assay of small molecules are not sensitive enough to quantitate the neuropeptides found within small subsections of individual neurons nor to detect the release of neurotransmitters from a single electrical stimulation. The long term objective of this research program is to develop and implement new analytical instrumentation and methodology to allow the identification and quantitation of the substances released from a single nerve terminal, and the measurement of the contents of individual varicosities along a single nerve process. The approach used to accomplish these goals is capillary electrophoresis followed by a unique multichannel laser-induced fluorescence detection system. Once the instrumentation and methodology is in place, neurotransmitter distribution and release will be studied using several different model systems including several identified neurons from the marine mollusks Aplysia californica and Pleurobranchaea californica and isolated nerve terminals from the cortex of the rat. These studies will answer the questions: do the neurons target different neurotransmitters to specific release sites, and can the neuron release different neurotransmitters at specific terminals? By using the advances in separation science and detector technology developed as part of this research, significant gains can be made in our understanding of the differential packing, distribution, and release of neurotransmitters. In leading to a description of the subcellular dynamics of neuronal signalling, this work will contribute to the basic understanding of the nervous system. The symptoms of many mental disorders suggest that an imbalance of chemical messengers may be responsible for the disease state. By answering questions of neurotransmitter targeting and release, we will gain further insight into how complex systems of neurons interact in both healthy and diseased systems.
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