Exploring local neuronal circuitry with controlled iontophoresis Public Deposited

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  • March 22, 2019
Creator
  • Belle, Anna
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Understanding how neurochemical messengers propagate neuronal signals and ensure delivery of nutrients to fuel this process is the first step to proper treatment and prevention of disorders involving neurological dysregulation. Here, the technique of controlled iontophoresis is coupled to electrochemical detection of dopamine, serotonin, and molecular oxygen (O2) and concurrent monitoring of cell firing to begin to probe the mechanics of local neural circuits. Iontophoresis is a drug delivery technique where application of current causes charged molecules to migrate through a glass capillary. In controlled iontophoresis these capillaries are coupled to a carbon-fiber microelectrode and ejections are monitored electrochemically. The ability to control and modify iontophoretic ejections in real-time makes controlled iontophoresis a significant advancement over previous iterations of iontophoresis as explained and demonstrated herein. Use of this technique first established that we can in fact selectively modulate electrically evoked dopamine release in the striatum of anesthetized rats with local application of an autoreceptor antagonist. Then, the technique was used to examine functional hyperemia, the link between cerebral blood flow and neurochemical release, by monitoring local changes in O2. Direct glutamate application, known to cause vasodilation, increased local O2 concentration linking these O2 changes to blood flow. Additionally, with controlled iontophoresis the relative concentrations of glutamate applied could be compared. This led to the discovery that application of high concentrations of glutamate induced ionic oscillations that are attributed to calcium. Next, the role of serotonin in functional hyperemia is examined in two regions with different serotonergic topography. Unlike glutamate, serotonin application is shown have a much more complex role in functional hyperemia, inducing increases, decreases, and no change in O2. Finally, in order to really understand neuronal signaling, it must be given a context. This work concludes with collection of concurrent electrochemical/electrophysiological data while controlled iontophoresis is used to selectively modulate dopamine release and cell firing in freely-moving animals engaged in behavioral tasks. Preliminary application of this technique has confirmed the existence of subpopulations of medium spiny neurons in the nucleus accumbens and shown that each of these subpopulations plays a unique role in intracranial self-stimulation.
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  • In Copyright
Advisor
  • Wightman, R. Mark
Degree
  • Doctor of Philosophy
Graduation year
  • 2013
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