ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Neurostimulation methods currently include deep brain stimulation (DBS), optogenetic, transcranial direct-current stimulation (tDCS), and transcranial magnetic stimulation (TMS). TMS and tDCS are noninvasive techniques whereas DBS and optogenetic require surgical implantation of electrodes or light emitting devices. All approaches, except for optogenetic, have been implemented in clinical settings because they have demonstrated therapeutic utility and clinical efficacy for neurological and psychiatric disorders. When applied for therapeutic applications, these techniques suffer from limitations that hinder the progression of its intended use to treat compromised brain function. DBS requires an invasive surgical procedure that surfaces complications from infection, longevity of electrical components, and immune responses to foreign materials. Both TMS and tDCS circumvent the problems seen with DBS as they are noninvasive procedures, but they fail to produce the spatial resolution required to target specific brain structures. Realizing these restrictions, we sought out to use ultrasound as a neurostimulation modality. Ultrasound is capable of achieving greater resolution than TMS and tDCS, as we have demonstrated a ~2mm lateral resolution, which can be delivered noninvasively. These characteristics place ultrasound superior to current neurostimulation methods. For these reasons, this dissertation provides a developed protocol to use transcranial pulsed ultrasound (TPU) as a neurostimulation technique. These investigations implement electrophysiological, optophysiological, immunohistological, and behavioral methods to elucidate the effects of ultrasound on the central nervous system and raise questions about the functional consequences. Intriguingly, we showed that TPU was also capable of stimulating intact sub-cortical circuits in the anesthetized mouse. These data reveal that TPU can evoke synchronous oscillations in the hippocampus in addition to increasing expression of brain-derived neurotrophic factor (BDNF). Considering these observations, and the ability to noninvasively stimulate neuronal activity on a mesoscale resolution, reveals a potential avenue to be effective in clinical settings where current brain stimulation techniques have shown to be beneficial. Thus, the results explained by this dissertation help to pronounce the significance for these protocols to gain translational recognition.
ContributorsTufail, Yusuf Zahid (Author) / Tyler, William J (Thesis advisor) / Duch, Carsten (Committee member) / Muthuswamy, Jitendran (Committee member) / Santello, Marco (Committee member) / Tillery, Stephen H (Committee member) / Arizona State University (Publisher)
Created2011
Description
Sensory gating is a process by which the nervous system preferentially admits stimuli that are important for the organism while filtering out those that may be meaningless. An optimal sensory gate cannot be static or inflexible, but rather plastic and informed by past experiences. Learning enables sensory gates to recognize stimuli that are emotionally salient and potentially predictive of positive or negative outcomes essential to survival. Olfaction is the only sensory modality in mammals where sensory inputs bypass conventional thalamic gating before entering higher emotional or cognitive brain regions. Thus, olfactory bulb circuits may have a heavier burden of sensory gating compared to other primary sensory circuits. How do the primary synapses in an olfactory system "learn"' in order to optimally gate or filter sensory stimuli? I hypothesize that centrifugal neuromodulator serotonin serves as a signaling mechanism by which primary olfactory circuits can experience learning informed sensory gating. To test my hypothesis, I conditioned genetically-modified mice using reward or fear olfactory-cued learning paradigms and used pharmacological, electrophysiological, immunohistochemical, and optical imaging approaches to assay changes in serotonin signaling or functional changes in primary olfactory circuits. My results indicate serotonin is a key mediator in the acquisition of olfactory fear memories through the activation of its type 2A receptors in the olfactory bulb. Functionally within the first synaptic relay of olfactory glomeruli, serotonin type 2A receptor activation decreases excitatory glutamatergic drive of olfactory sensory neurons through both presynaptic and postsynaptic mechanisms. I propose that serotonergic signaling decreases excitatory drive, thereby disconnecting olfactory sensory neurons from odor responses once information is learned and its behavioral significance is consolidated. I found that learning induced chronic changes in the density of serotonin fibers and receptors, which persisted in glomeruli encoding the conditioning odor. Such persistent changes could represent a sensory gate stabilized by memory. I hypothesize this ensures that the glomerulus encoding meaningful odors are much more sensitive to future serotonin signaling as such arousal cues arrive from centrifugal pathways originating in the dorsal raphe nucleus. The results advocate that a simple associative memory trace can be formed at primary sensory synapses to facilitate optimal sensory gating in mammalian olfaction.
ContributorsLi, Monica (Author) / Tyler, William J (Thesis advisor) / Smith, Brian H. (Thesis advisor) / Duch, Carsten (Committee member) / Neisewander, Janet (Committee member) / Vu, Eric (Committee member) / Arizona State University (Publisher)
Created2012