MULTIMODAL SENSING FOR OXYGEN AND NEUROTRANSMITTERS IN THE DEEP BRAIN

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  • March 20, 2019
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  • Hobbs, Caddy
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Communication among cells in the brain is responsible for sensory perception, motivation, movement, learning, memory and more. Neurotransmitters are messenger molecules that are released in an energy-consuming process known as the action potential. Interaction between brain cells and the vasculature (i.e., neurovascular coupling) ensures that adequate blood flow is delivered to meet the energy demands of active brain regions. Much research is focused on neurovascular communication because dysregulation in these pathways is implicated in disease states, such as stroke, Alzheimer’s, addiction, and depression. Because neuronal signaling is a dynamic process that involves the cooperative action of an array of chemical mediators, an ideal monitoring technique should detect changes in multiple compounds of interest on relevant timescales and thus enable researchers to interpret coincident effects. Here, we present fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes as a powerful technique for real-time, multimodal recordings of chemical and electrophysiological changes in distinct brain regions. FSCV produces multivariate data sets that distinguish multiple compounds of interest, as well as identifying interfering signals. First, we characterize interfering signals that arise from ionic changes in the extracellular space and investigate methods for increasing catecholamine-generated signal on an extended voltammetric waveform for simultaneous detection of oxygen. Next, physiological neurovascular coupling is investigated, with respect to the effects mediated by the neurotransmitter serotonin. Finally, we expand the utility of FSCV by coupling it with DC electrophysiological recordings for probing changes that occur during the pathophysiological phenomenon of spreading depolarization (SD). SD represents one of the largest concomitant changes in chemicals and electrophysiology that occur in brain tissue. As such, our multimodal sensor fulfills a deficiency in SD research for a minimally-invasive technique capable of recording in either cortical or deeper brain tissues. We characterize highly reproducible oxygen, neurotransmitter, and electrophysiological changes to successive SD events. Further, we probed erstwhile undetected regional variability in oxygen responses and also investigated the effect of dopamine neurotransmission on SD waves. Our results advance current understandings of neuronal communication and promote FSCV’s use for future research at physiologically-relevant spatial and temporal resolutions.
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  • In Copyright
Advisor
  • Lockett, Matthew
  • Manis, Paul B.
  • Jorgenson, James
  • Carelli, Regina
  • Wightman, R. Mark
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2017
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