Nerve cells, or neurons, receive inputs from other neurons predominantly within their dendrites, highly branched structures emanating from the cell body. In many neurons, the patterns of dendrites are refined during development, through a process that is dependent on the activity of the input neurons. This process has been hypothesized to eliminate parts of the dendrites that receive erroneous inputs, thus "hardwiring" the neurons for maximal efficiency.
This project employs cultures containing spinal cord motor neurons to investigate how these neurons use electrical activity to accomplish refinement of their dendrites. Real-time imaging will be performed to examine how rates of growth, elongation and elimination of dendritic segments are affected by the neurotransmitter glutamate binding to specific glutamate receptors on the cell surface. Fluorescent-tagged glutamate receptors will be introduced into neurons, to determine whether these are co-localized at areas of dynamic growth or retraction of dendrites. In addition, level of gene expression for each receptor will be measured using a quantitative PCR method, to determine how the availability of each receptor is controlled during the development of motor neurons. Finally, levels of glutamate receptor expression will be experimentally reduced, to investigate whether dendrite growth is compromised. These studies are important because they will provide information regarding how developing neurons attain patterns of connectivity by altering their ability to respond to neurotransmitters.
The broader impact of this proposal includes significant enhancement of graduate and undergraduate scholarship and research at Tulane University. The integration of current research strategies into graduate and undergraduate training and classroom discussions will promote neuroscience as a subject for study throughout the higher education system.
