Neurotransmitter Interactions on Sub-Second Timescales

Prof. Michael Johnson, Department of Chemistry
University of Kansas

Project dates: 2012-2015

Mentor: Craig Lunte

Sub-second concentration changes of extracellular dopamine—a CNS neurotransmitter that is involved in cognition, addiction, reward, and movement—are governed by its vesicular release from pre-synaptic terminals and its subsequent uptake by membrane-bound protein transporters. Importantly, these signaling events are thought to be modulated by glutamate and γ-aminobutyric acid (GABA), two abundant amino acid neurotransmitters, within the sub-second time regime; however, the particular mechanisms underlying this control, and their relevance to human disease, are not well-known largely because the analytical methodology needed to address these important questions has not been sufficiently developed.

This deficiency represents a significant roadblock toward understanding neurological function because signaling events in the brain that influence outward physical responses and cognitive events occur within this sub-second time regime. The central aim of Dr. Johnson’s proposed research is to develop and apply tools that will allow for the quantitative study of these neurotransmitter interactions in tissues and in vivo. Fast-scan cyclic voltammetry (FSCV) at 5 μm-diameter carbon-fiber microelectrodes, used to measure the sub-second release of dopamine, will be combined and temporally-aligned with the μs-timescale photo-activation of p-hydroxyphenyl-caged form of glutamate (pHP-Glu) in brain slices.  This method will be used to test the hypothesis that dopamine release impairments found in rodents that model Huntington’s disease are a result of an amplified response to glutamate signaling.  Additionally, the Johnson group will develop and deploy a microfluidic platform designed to examine the effects of caged compound photoactivation on brain tissue slices.

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