Michael A. Johnson

Bioanalytical chemistry; microsensor development; microfluidics; electrochemical detection of neurotransmitters; fluorescence microscopy; neurological disorders; oxidative stress.

The goal of my research program is the development and application of bioanalytical techniques for studying how neurons communicate with each other. A wide array of techniques are employed, including fluorescence microscopy, caged compound photolysis, microfluidics, biochemical methods, behavioral techniques, and state-of-the-art electrochemical techniques that allow for the monitoring of biogenic molecules on physiologically relevant time scales. These methods are used to study a variety of important problems, including neurological disorders, oxidative stress, and mechanisms of drug action.

Huntington’s disease. Huntington’s disease (HD) is a neurodegenerative disorder characterized by uncontrollable muscle movements and mental illness. HD patients typically die 15 to 20 years following symptom onset. We and others have recently discovered that release of dopamine, a key neurotransmitter in motor and cognitive signaling, is sharply attenuated in animal models of HD. To understand the contributions of abnormal neurotransmitter release in the debilitating motor symptoms of HD, electrochemical techniques have been applied in vivo to animal models of HD. Additionally, microscopy techniques are applied to study tissue sections in these animal models to yield clues regarding mechanisms of altered signaling.

Chemobrain. “Chemobrain” is a decline in cognitive function experienced by patients undergoing chemotherapy treatment. Recent studies comparing cognitive function before and after chemotherapy suggest that approximately 20-30% of cancer patients will exhibit lower cognitive performance after chemotherapy than would be expected. Developing an understanding of chemobrain is becoming more important as the survival rates of cancers continue to increase. We are currently employing electrochemical and behavioral techniques in order to unravel the underlying mechanisms of chemobrain.

Oxidative Stress and Neurotransmission. A strong connection has been established between oxidative stress and many neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, and Lou Gehrig’s disease. We are interested in the effects of oxidative stress on neuronal function. Electrochemical and microscopy techniques are used to characterize release and uptake processes in models of oxidative stress.

Caged Compound Photolysis. Our research group is combining caged compound photolysis with fast-scan cyclic voltammetry measurements in order to resolve neurotransmitter interactions. Caged compounds are molecules that can release a molecular ‘cage’ upon exposure to light of sufficient energy. Here, we make use of the p-hydroxyphenacyl and coumarin cages to render bioactive molecules inactive. We then use a microscopy or a fiber-optic cable to supply ultraviolet and visible light in order to bioactivate the molecule on millisecond timescales. Immediate changes in neurotransmitter release are monitored using fast-scan cyclic voltammetry.

Microfluidic devices. We are pursuing the development and use of microfluidic devices for the study of neurotransmitter/neuromodulator release from brain slices. This approach will be combined with caged compound photoactivation as well.