Expression of transmitter phenotype in neurons, both during development and in the adult, results from a number of complex interactions that occur both within and between neurons. To examine these issues my laboratory utilizes the model of afferent regulation of catecholamine gene expression in the olfactory system. Either peripheral afferent denervation or odorant (sensory) deprivation of the olfactory bulb produces profound changes in activity, immunoreactivity and mRNA levels for tyrosine hydroxylase (TH), the first enzyme in the catecholamine biosynthetic pathway and the rate-limiting enzyme in dopamine biosynthesis. Immunocytochemical, biochemical, and in situ hybridization analyses are employed to further characterize the role of afferent innervation in TH expression. Molecular biological analysis of the TH promoter investigates the process of induction of phenotype in developing animals and mechanisms underlying plasticity of transmitter expression in adults.

In addition, phenotypic expression during aging is being studied because olfactory function is compromised both in normal aging and in neurodegenerative syndromes, such as Alzheimer's and Parkinson's diseases. The mechanism for these changes is unknown, but could involve effects primary or secondary to altered afferent innervation. Furthermore, the olfactory system serves as a conduit for entry of some toxins and viruses to the brain. Both the extent and metabolic effects of the entry of xenobiotics into the CNS are pursued in the laboratory.