The progression of Parkinson’s disease (PD) is associated with the loss of neurons in a specific area of the brain called the substantia nigra. The neurons lost in PD use dopamine as their neurotransmitter and are required for normal movement control. Dopamine is also found in neurons in other areas of the brain, including the olfactory bulb. My laboratory is interested in the dopamine producing neurons of the olfactory system.
At one time it was thought that neurons were only produced during gestation but these neurons are even generated in adults, from stem cells. The olfactory system may be a possible source of stem cells that can be used to replace the damaged neurons. Understanding where these neurons arise, the signals involved in determining the pathway by which these cells migrate to their proper location, and why only some of the cells become dopamine neurons are among the questions we are studying.
My laboratory uses a number of model systems to study the dopamine neurons. One of these systems uses mice that express a green fluorescent protein in the dopamine neurons, allowing us to follow their migration. Dopamine synthesis in the olfactory bulb is also regulated by odor stimulation. To study the molecular mechanisms underlying dopamine biosynthesis, we use a model in which access of odor molecules to the nose is blocked.
Our long-term goals are to determine if there is a unique olfactory stem cell that produces interneurons with a dopamine phenotype, to determine how it becomes a dopamine neuron, and to discover the mechanisms regulating dopamine synthesis in the mature neuron. The answers may lead to replacement of the dopamine-producing neurons that are destroyed in Parkinson’s and other neurodegenerative diseases.