Graduate Training in Neuroscience
University of Washington
Richard D. Palmiter
Professor, Department of Biochemistry; Investigator, HHMI
Dr. Palmiter's lab uses genetic techniques to explore the role of neurotransmitters in the development and function of the mammalian nervous system. Most recently they have used gene inactivation methods to produce mice that cannot make noradrenaline, dopamine, or neuropeptide Y. Mice that cannot make noradrenaline die as embryos but they can be rescued to birth pharmacologically. After birth they develop quite normally without further intervention. However, they are very cold sensitive, males are infertile, females are poor mothers and there are numerous subtle learning and motor deficits. Mice that cannot make dopamine are born and begin to grow normally but after about 2 weeks of age they become hypoactive and stop nursing and will die without intervention. They can be rescued by daily administration of L-DOPA. The role of dopamine in the regulation of appetite is particularly intriguing. The lab is using pharmacological, genetic and gene therapy approaches to dissect the pathways involved. The lab has also been exploring the function of NPY because injection of NPY into the brain stimulates voracious feeding; however, mice lacking NPY eat and grow normally. The lab is trying to understand the discrepancy between the pharmacological and genetic results. This lab is also studying the role of zinc as a neuromodulator. Zinc is packaged in synaptic vesicles with glutamate in some neurons. The lab has produced mice that cannot transport zinc into the vesicles and is now studying their behavior. The overall effect of removing zinc from synaptic vesicles is heightened neural excitability which manifests as increased susceptibility to epileptic seizures. This suggests that zinc is an inhibitory neuromodulator but the receptor(s) involved are not known.