Extrasynaptic communication (volume transmission) between neurons is an intriguing, yet elusive concept. Dopamine (DA) can act as an extrasynaptic as well as a synaptic transmitter and is particularly important because of its roles in Parkinson's disease, drug addiction, and other aspects of psychopharmacology. Its behavior in the CNS can be monitored directly using carbon fiber microelectrodes and voltammetry. We are addressing how DA mediates volume transmission by determining the relative influence of uptake and diffusion on its migration in DA terminal regions like striatum, and studying the process of non-classical, dendritic release of DA in cell body regions like substantia nigra. Our long-term goal is to assess extrasynaptic transmission as a general means of communication in the CNS.

Oxidative metabolism produces reactive oxygen species that threaten cell integrity. A network of cellular antioxidants work together to prevent oxidative damage. Ascorbate and GSH contribute to the first line of defense in this process, yet surprisingly little is known about their regulation in the CNS. We have suggested that they have complementary, but distinct roles, with ascorbate localized in high concentration in neurons, but low concentration in glia, where GSH predominates. Overall brain levels of ascorbate, but not GSH, are also high in anoxia-tolerant species like pond turtles. Our experiments to investigate the roles of ascorbate and GSH in the CNS use HPLC, voltammetric and ion-selective microelectrodes, and histological and physiological techniques. Questions being addressed include how gender influences ascorbate regulation and how conditions that disrupt regulation, including cerebral ischemia, cause oxidative stress.