METHODS AND APPLICATIONS FOR FAST-SCAN CYCLIC VOLTAMMETRIC DETECTION OF IN VIVO CATECHOLAMINE DYNAMICS Public Deposited

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  • March 19, 2019
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  • Bucher, Elizabeth
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes provides the spatial, temporal and chemical resolution required to study rapid catecholamine dynamics in the brain. It is most well-known for its use in dopamine studies, where it has contributed much to our knowledge regarding the presynaptic regulation of dopamine as well as its role reward learning and addiction. Only recently has FSCV been applied to the detection of norepinephrine, the other major catecholamine neurotransmitter in the central nervous system. This is largely due to issues of selectivity; the electrochemistry of dopamine and norepinephrine is indistinguishable with FSCV. For dopamine selectivity is not as much of an issue as there are large regions of the brain innervated by dopamine neurons that lack major noradrenergic input. For norepinephrine, however, there are only a few noradrenergic terminal regions that receive little dopamine innervation and the small size of these regions (typically ~ 0.5 mm3) make them difficult, but not impossible, to target. Five years ago, it was demonstrated through electrochemical, chemical, anatomical and pharmacological assays that norepinephrine could be monitored selectively with FSCV in ventral subregion of the bed nucleus of the stria terminalis (vBNST), a limbic structure that integrates cognitive and sensory information to initiate the physiological and behavioral responses to stress, including glucocorticoid secretion via the HPA axis. Norepinephrine signaling within the BNST is thought to potentiate these processes, and its dysregulation is widely implicated in anxiety-related conditions such as post-traumatic stress disorder (PTSD). Initial recordings within the vBNST have revealed that norepinephrine can release can be evoked by electrical stimulation of the dorsal and ventral noradrenergic axon pathways, that it is regulated by the norepinephrine autoreceptor and transporter, and have confirmed that, like dopamine, it is modulated by stimulation frequency and pulse number. Additional work has established that BNST norepinephrine dynamics can be recorded in awake, freely-moving rats and that it oppositely responds to administration of aversive and appetitive tastants. The studies presented in this volume are an extension of this preliminary work and explore several facets of norepinephrine signaling within the BNST with FSCV in anesthetized and behaving animals. Chapter 2 investigates the neural pathways by which electrical stimulation evokes norepinephrine release within the BNST. Chapters 3 and 4 compares the responses of norepinephrine in the BNST and dopamine the NAc, a related limbic structure, during an aversive sensory stimulation and during reward learning and extinction. Chapter 5 employs combined iontophoresis and FSCV to probe the local mechanisms by which BNST norepinephrine regulates hemodynamic function during neuronal activity. Finally, Chapter 6 and 7 describe and assess new experimental tools for FSCV data collection and analysis. Together the results of these studies demonstrate the utility of FSCV in the detection of rapid norepinephrine signaling in vivo and provide new information regarding the dual role of BNST norepinephrine as a neuro- and vaso-modulator.
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  • In Copyright
Advisor
  • Lockett, Matthew
  • Manis, Paul B.
  • Wightman, R. Mark
  • Carelli, Regina
  • Murray, Royce W.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
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  • Chapel Hill, NC
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