This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Lurie[unreadable]s laboratory investigates the effects and mechanisms of very low levels of lead (Pb) exposure on auditory function. Using proteomic, immunohistochemistry, and microarray technology, they have found that Pb alters the phosphorylation state of neurofilament, changes the expression of synaptic proteins including synaptophysin and nicotinic receptors, and changes the expression of kinesin motor proteins. These motor proteins are important for trafficking both neurofilament and various synaptic proteins to their proper locations within the cell. In addition, Pb appears to modulate proteins that connect the actin cytoskeleton with various membrane proteins. All of these changes could have an impact on how electrical signals are transmitted by neurons through the auditory system. Their University of Rochester collaborator, Dr. Joseph Walton, has found that Pb appears to directly affect the neural connection between auditory nerve cells in the brainstem. This is important because we will now be able to determine how manipulation of cellular systems that may be affected by Pb can alter the neural connections of auditory nuclei. This work is demonstrating that very low levels of Pb (below levels that are considered safe) can result in very significant changes within brain cells. These results, combined with our previous studies of Pb on the avian CNS and on avian behavior have resulted in a submission of a major grant proposal to the NIH.