The sense of smell influences many intriguing aspects of human and animal behavior. Scents elicit innate responses of attraction and revulsion and evoke enduring emotional memories. These features suggest that behaviorally important olfactory neural circuits may be hard-wired. We are interested in understanding how genes build specific neural circuits. We use gene targeting in embryonic stem cells, molecular biology and imaging to visualize and modify the neurons that recognize odors in the periphery and the brain. By labeling and defining the specific neural circuits involved in olfaction we hope to identify genes that regulate neural circuit formation in general. These studies are critical first steps toward understanding how neural circuits produce sensory perception and how genetic alterations may contribute to neuronal dysfunction and cognitive disorders. In addition to reversible genetic changes, neurons have been postulated to undergo irreversible chromosomal alterations during development, aging and disease, however no such alterations have been identified. The diversity and post-mitotic state of neurons has hindered these studies - at present there is no unbiased method to survey the genome of an individual neuron. A major focus of the lab is to develop such a method by using somatic cell nuclear transfer technology to generate cloned mice or embryonic stem cell lines from defined subsets of neurons. These studies will determine, for the first time, whether it is possible to clone mice from adult cortical neurons and will provide a novel means to understand how chromosomal alterations in neurons may contribute to neuronal differentiation or neurodegenerative diseases.