PittCon 2000: Abstract #1343

Electrochemical Strategies for selective Neurochemical monitoring in the extracellular space of living brain tissue

ADRIAN C. MICHAEL, NADEZHDA KULAGINA, JUN CUI, Department of Chemistry, University of Pittsburgh, Pittsburgh,  PA 15260

Recently, there have been major developments in the technologies available for the chemical analysis of the living brain. These technologies have already made their way into both clinical and fundamental research laboratories and are enabling significant advances in our knowledge of the properties and function of the central nervous system. These advances are enabling improvements in our basic understanding of, for example, brain injury, neurodegenerative diseases, psychiatric disorders, and drug addiction.

Chemical monitoring in the extracellular space of the brain is an important, yet challenging, task. If sensors are to be implanted directly into the brain tissue of living animals, they should be small enough to minimize trauma, they should be selective, they should provide adequate sensitivity, and their temporal response should be faster than the time scale of the biological processes under investigation. Electrochemical microsensors prepared by chemical modification of carbon fiber microelectrodes meet these criteria in several cases. These devices can be used to directly probe the neurochemical activity of the brain and are proving extremely valuable in the context of fundamental neuroscience research.

Carbon fiber electrodes can be used in conjunction with fast scan cyclic voltammetry procedures to monitor extracellular levels of the neurotransmitter, dopamine, in brain tissue. Appropriate chemical modification and the incorporation of amperometric monitoring procedures allows detection of glutamate, choline, ascorbate, and glucose.

Many questions surround the interactions between the dopaminergic and glutamatergic neuronal pathways that converge on brain structures known collectively as the basal ganglia, which are intimately involved in Parkinson’s disease, Alzheimer’s disease, and drug abuse. Measurements both in an in vitro tissue preparation and directly in living tissue of the rat are being used to investigate dopamine:glutamate interactions. In both preparations, drugs that block ionotropic glutamate receptors have been noticed to have significant impact on dopaminergic responses. This demonstrates that glutamate can regulate the activity of dopamine terminals even though the dopamine terminals do not receive synaptic input from glutamate terminals.  One implication of these results is the suggestion that glutamate may act as chemical messenger outside the synaptic space of brain tissue.