Beckman Fellow 1993-94

Jonathan V. Sweedler


Subcellular Neurotransmitter Distribution and Release

As 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 in contemporary neuroscience is to understand the cellular mechanisms responsible for neurotransmitter targeting and release. Essential to an understanding of neurotransmitter release is knowledge of the amounts and locations of neurotransmitters present in the neuron; because of technology limitations, this information is not currently available. One of the long-term objectives of this research program is to develop and implement new analytical instrumentation and methodology to allow the identification and quatitation of the contents of individual varicosities along a single nerve process. Once the instrumentation is in place, subcellular neurotransmitter distribution and release will be studied using several different model neuronal systems from the marine snail Aplysia californica. These studies are aimed at answering the questions: does a neuron target different neurotransmitters to specific release sites, and can a 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 understanding 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, Professor Sweedler gains further insight into how complex systems of neurons interact in both healthy and diseased systems.