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- Creators: Arizona State University
Description
Spatiotemporal processing in the mammalian olfactory bulb (OB), and its analog, the invertebrate antennal lobe (AL), is subject to plasticity driven by biogenic amines. I study plasticity using honey bees, which have been extensively studied with respect to nonassociative and associative based olfactory learning and memory. Octopamine (OA) release in the AL is the functional analog to epinephrine in the OB. Blockade of OA receptors in the AL blocks plasticity induced changes in behavior. I have now begun to test specific hypotheses related to how this biogenic amine might be involved in plasticity in neural circuits within the AL. OA acts via different receptor subtypes, AmOA1, which gates calcium release from intracellular stores, and AmOA-beta, which results in an increase of cAMP. Calcium also enters AL interneurons via nicotinic acetylcholine receptors, which are driven by acetylcholine release from sensory neuron terminals, as well as through voltage-gated calcium channels. I employ 2-photon excitation (2PE) microscopy using fluorescent calcium indicators to investigate potential sources of plasticity as revealed by calcium fluctuations in AL projection neuron (PN) dendrites in vivo. PNs are analogous to mitral cells in the OB and have dendritic processes that show calcium increases in response to odor stimulation. These calcium signals frequently change after association of odor with appetitive reinforcement. However, it is unclear whether the reported plasticity in calcium signals are due to changes intrinsic to the PNs or to changes in other neural components of the network. My studies were aimed toward understanding the role of OA for establishing associative plasticity in the AL network. Accordingly, I developed a treatment that isolates intact, functioning PNs in vivo. A second study revealed that cAMP is a likely component of plasticity in the AL, thus implicating the AmOA-beta; receptors. Finally, I developed a method for loading calcium indicators into neural components of the AL that have yet to be studied in detail. These manipulations are now revealing the molecular mechanisms contributing to associative plasticity in the AL. These studies will allow for a greater understanding of plasticity in several neural components of the honey bee AL and mammalian OB.
ContributorsProtas, Danielle (Author) / Smith, Brian H. (Thesis advisor) / Neisewander, Janet (Committee member) / Anderson, Trent (Committee member) / Tyler, William (Committee member) / Vu, Eric (Committee member) / Arizona State University (Publisher)
Created2014
Description
Music training is associated with measurable physiologic changes in the auditory pathway. Benefits of music training have also been demonstrated in the areas of working memory, auditory attention, and speech perception in noise. The purpose of this study was to determine whether long-term auditory experience secondary to music training enhances the ability to detect, learn, and recall new words.
Participants consisted of 20 young adult musicians and 20 age-matched non-musicians. In addition to completing word recognition and non-word detection tasks, each participant learned 10 nonsense words in a rapid word-learning task. All tasks were completed in quiet and in multi-talker babble. Next-day retention of the learned words was examined in isolation and in context. Cortical auditory evoked responses to vowel stimuli were recorded to obtain latencies and amplitudes for the N1, P2, and P3a components. Performance was compared across groups and listening conditions. Correlations between the behavioral tasks and the cortical auditory evoked responses were also examined.
No differences were found between groups (musicians vs. non-musicians) on any of the behavioral tasks. Nor did the groups differ in cortical auditory evoked response latencies or amplitudes, with the exception of P2 latencies, which were significantly longer in musicians than in non-musicians. Performance was significantly poorer in babble than in quiet on word recognition and non-word detection, but not on word learning, learned-word retention, or learned-word detection. CAEP latencies collapsed across group were significantly longer and amplitudes were significantly smaller in babble than in quiet. P2 latencies in quiet were positively correlated with word recognition in quiet, while P3a latencies in babble were positively correlated with word recognition and learned-word detection in babble. No other significant correlations were observed between CAEPs and performance on behavioral tasks.
These results indicated that, for young normal-hearing adults, auditory experience resulting from long-term music training did not provide an advantage for learning new information in either favorable (quiet) or unfavorable (babble) listening conditions. Results of the present study suggest that the relationship between music training and the strength of cortical auditory evoked responses may be more complex or too weak to be observed in this population.
Participants consisted of 20 young adult musicians and 20 age-matched non-musicians. In addition to completing word recognition and non-word detection tasks, each participant learned 10 nonsense words in a rapid word-learning task. All tasks were completed in quiet and in multi-talker babble. Next-day retention of the learned words was examined in isolation and in context. Cortical auditory evoked responses to vowel stimuli were recorded to obtain latencies and amplitudes for the N1, P2, and P3a components. Performance was compared across groups and listening conditions. Correlations between the behavioral tasks and the cortical auditory evoked responses were also examined.
No differences were found between groups (musicians vs. non-musicians) on any of the behavioral tasks. Nor did the groups differ in cortical auditory evoked response latencies or amplitudes, with the exception of P2 latencies, which were significantly longer in musicians than in non-musicians. Performance was significantly poorer in babble than in quiet on word recognition and non-word detection, but not on word learning, learned-word retention, or learned-word detection. CAEP latencies collapsed across group were significantly longer and amplitudes were significantly smaller in babble than in quiet. P2 latencies in quiet were positively correlated with word recognition in quiet, while P3a latencies in babble were positively correlated with word recognition and learned-word detection in babble. No other significant correlations were observed between CAEPs and performance on behavioral tasks.
These results indicated that, for young normal-hearing adults, auditory experience resulting from long-term music training did not provide an advantage for learning new information in either favorable (quiet) or unfavorable (babble) listening conditions. Results of the present study suggest that the relationship between music training and the strength of cortical auditory evoked responses may be more complex or too weak to be observed in this population.
ContributorsStewart, Elizabeth (Author) / Pittman, Andrea (Thesis advisor) / Cone, Barbara (Committee member) / Zhou, Yi (Committee member) / Arizona State University (Publisher)
Created2017
Description
The ability to detect and appropriately respond to chemical stimuli is important for many organisms, ranging from bacteria to multicellular animals. Responses to these stimuli can be plastic over multiple time scales. In the short-term, the synaptic strengths of neurons embedded in neural circuits can be modified and result in various forms of learning. In the long-term, the overall developmental trajectory of the olfactory network can be altered and synaptic strengths can be modified on a broad scale as a direct result of long-term (chronic) stimulus experience. Over evolutionary time the olfactory system can impose selection pressures that affect the odorants used in communication networks. On short time scales, I measured the effects of repeated alarm pheromone exposure on the colony-level defense behaviors in a social bee. I found that the responses to the alarm pheromone were plastic. This suggests that there may be mechanisms that affect individual plasticity to pheromones and regulate how these individuals act in groups to coordinate nest defense. On longer time scales, I measured the behavioral and neural affects of bees given a single chronic odor experience versus bees that had a natural, more diverse olfactory experience. The central brains of bees with a deprived odor experience responded more similarly to odorants in imaging studies, and did not develop a fully mature olfactory network. Additionally, these immature networks showed behavioral deficits when recalling odor mixture components. Over evolutionary time, signals need to engage the attention of and be easily recognized by bees. I measured responses of bees to a floral mixture and its constituent monomolecular components. I found that natural floral mixtures engage the orientation of bees’ antennae more strongly than single-component odorants and also provide more consistent central brain responses between stimulations. Together, these studies highlight the importance of olfactory experience on different scales and how the nervous system might impose pressures to select the stimuli used as signals in communication networks.
ContributorsJernigan, Christopher (Author) / Smith, Brian H. (Thesis advisor) / Newbern, Jason (Committee member) / Harrisoin, Jon (Committee member) / Rutowski, Ronald (Committee member) / Pratt, Stephen (Committee member) / Arizona State University (Publisher)
Created2018
Description
Childhood Apraxia of Speech (CAS) is a severe motor speech disorder that is difficult to diagnose as there is currently no gold-standard measurement to differentiate between CAS and other speech disorders. In the present study, we investigate underlying biomarkers associated with CAS in addition to enhanced phenotyping through behavioral testing. Cortical electrophysiological measures were utilized to investigate differences in neural activation in response to native and non-native vowel contrasts between children with CAS and typically developing peers. Genetic analysis included full exome sequencing of a child with CAS and his unaffected parents in order to uncover underlying genetic variation that may be causal to the child’s severely impaired speech and language. Enhanced phenotyping was completed through extensive behavioral testing, including speech, language, reading, spelling, phonological awareness, gross/fine motor, and oral and hand motor tasks. Results from cortical electrophysiological measures are consistent with previous evidence of a heightened neural response to non-native sounds in CAS, potentially indicating over specified phonological representations in this population. Results of exome sequencing suggest multiple genetic variations contributing to the severely affected phenotype in the child and provide further evidence of heterogeneous genomic pathways associated with CAS. Finally, results of behavioral testing demonstrate significant impairments evident across tasks in CAS, suggesting underlying sequential processing deficits in multiple domains. Overall, these results have the potential to delineate functional pathways from genetic variations to the brain to observable behavioral phenotypes and motivate the development of preventative and targeted treatment approaches.
ContributorsVose, Caitlin (Author) / Peter, Beate (Thesis advisor) / Liu, Li (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2018
Description
Myocardial infarction (MI) remains the leading cause of mortality and morbidity in the U.S., accounting for nearly 140,000 deaths per year. Heart transplantation and implantation of mechanical assist devices are the options of last resort for intractable heart failure, but these are limited by lack of organ donors and potential surgical complications. In this regard, there is an urgent need for developing new effective therapeutic strategies to induce regeneration and restore the loss contractility of infarcted myocardium. Over the past decades, regenerative medicine has emerged as a promising strategy to develop scaffold-free cell therapies and scaffold-based cardiac patches as potential approaches for MI treatment. Despite the progress, there are still critical shortcomings associated with these approaches regarding low cell retention, lack of global cardiomyocytes (CMs) synchronicity, as well as poor maturation and engraftment of the transplanted cells within the native myocardium. The overarching objective of this dissertation was to develop two classes of nanoengineered cardiac patches and scaffold-free microtissues with superior electrical, structural, and biological characteristics to address the limitations of previously developed tissue models. An integrated strategy, based on micro- and nanoscale technologies, was utilized to fabricate the proposed tissue models using functionalized gold nanomaterials (GNMs). Furthermore, comprehensive mechanistic studies were carried out to assess the influence of conductive GNMs on the electrophysiology and maturity of the engineered cardiac tissues. Specifically, the role of mechanical stiffness and nano-scale topographies of the scaffold, due to the incorporation of GNMs, on cardiac cells phenotype, contractility, and excitability were dissected from the scaffold’s electrical conductivity. In addition, the influence of GNMs on conduction velocity of CMs was investigated in both coupled and uncoupled gap junctions using microelectrode array technology. Overall, the key contributions of this work were to generate new classes of electrically conductive cardiac patches and scaffold-free microtissues and to mechanistically investigate the influence of conductive GNMs on maturation and electrophysiology of the engineered tissues.
ContributorsNavaei, Ali (Author) / Nikkhah, Mehdi (Thesis advisor) / Brafman, David (Committee member) / Migrino, Raymond Q. (Committee member) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2018
Description
ABSTRACT Communication is vital in the context of everyday life for all organisms, but particularly so in social insects, such as Z. nevadensis. The overall lifestyle and need for altruistic acts of individuals within a colony depends primarily on intracolony chemical communication, with a focus on odorants. The perception of these odorants is made possible by the chemoreceptive functions of sensilla basiconica and sensilla trichoid which exist on the antennal structure. The present study consists of both a morphological analysis and electrophysiological experiment concerning sensilla basiconica. It attempts to characterize the function of neurons present in sensilla basiconica through single sensillum recordings and contributes to existing literature by determining if a social insect, such as the dampwood termite, is able to perceive a wide spectrum of odorants despite having significantly fewer olfactory receptors than most other social insect species. Results indicated that sensilla basiconica presence significantly out-paced that of sensilla trichoid and sensilla chaetica combined, on all flagellomeres. Analysis demonstrated significant responses to all general odorants and several cuticular hydrocarbons. Combined with the knowledge of fewer olfactory receptors present in this species and their lifestyle, results may indicate a positive association between the the social complexity of an insect's lifestyle and the number of ORs the individuals within that colony possess.
ContributorsMcGlone, Taylor (Author) / Liebig, Juergen (Thesis director) / Ghaninia, Majid (Committee member) / Barrett, The Honors College (Contributor)
Created2015-05
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
Description
Information processing in the brain is mediated by network interactions between anatomically distant (centimeters apart) regions of cortex and network action is fundamental to human behavior. Disruptive activity of these networks may allow a variety of diseases to develop. Degradation or loss of network function in the brain can affect many aspects of the human experience; motor disorder, language difficulties, memory loss, mood swings, and more. The cortico-basal ganglia loop is a system of networks in the brain between the cortex, basal ganglia, the thalamus, and back to the cortex. It is not one singular circuit, but rather a series of parallel circuits that are relevant towards motor output, motor planning, and motivation and reward. Studying the relationship between basal ganglia neurons and cortical local field potentials may lead to insights about neurodegenerative diseases and how these diseases change the cortico-basal ganglia circuit. Speech and language are uniquely human and require the coactivation of several brain regions. The various aspects of language are spread over the temporal lobe and parts of the occipital, parietal, and frontal lobe. However, the core network for speech production involves collaboration between phonologic retrieval (encoding ideas into syllabic representations) from Wernicke’s area, and phonemic encoding (translating syllables into motor articulations) from Broca’s area. Studying the coactivation of these brain regions during a repetitive speech production task may lead to a greater understanding of their electrophysiological functional connectivity. The primary purpose of the work presented in this document is to validate the use of subdural microelectrodes in electrophysiological functional connectivity research as these devices best match the spatial and temporal scales of brain activity. Neuron populations in the cortex are organized into functional units called cortical columns. These cortical columns operate on the sub-millisecond temporal and millimeter spatial scale. The study of brain networks, both in healthy and unwell individuals, may reveal new methodologies of treatment or management for disease and injury, as well as contribute to our scientific understanding of how the brain works.
ContributorsO'Neill, Kevin John (Author) / Greger, Bradley (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen (Committee member) / Papandreou-Suppapola, Antonia (Committee member) / Kleim, Jeffery (Committee member) / Arizona State University (Publisher)
Created2021
Description
Honeybees require the use of their antennae to perceive different scents and pheromones, communicate with other members of the colony, and even detect wind vibrations, sound waves, and carbon dioxide levels. Limiting and/or removing this sense makes bees much less effective at acquiring information. However, how antennal movements might be important for olfaction has not been studied in detail. The focus of this work was to evaluate how restriction of antennae movements might affect a bee’s ability to detect and perceive odors. Bees were made to learn a certain odor and were then split up into a control group, a treatment group that had their antennae fixed with eicosane, and a sham treatment group that had a dot of eicosane on their heads in such a way that it would not affect antennae movements but still add the same amount of weight. Following a period of acclimation, the bees were tested with the conditioned odor, one that was perceptually similar to it, and to a dissimilar odor. Using proboscis-extension duration and latency as response measures, it became clear that both antenna fixation and sham treatments affected the conditioned behavior. However, these treatment effects did not reach statistical significance. Briefly, both fixation of antennae as well as the sham treatment reduced the discriminability of the conditioned and similar odors. Although more data can be collected to more fully evaluate the significance of the treatments, the behavior of the sham group could indicate that mechanoreceptive hairs on the head play an important role in olfaction. It is also possible that there are other factors at play, possibly induced by the fixed bees’ increased stress levels.
ContributorsHozan, Alvin Robert (Author) / Smith, Brian H (Thesis advisor) / Lei, Hong (Committee member) / Cook, Chelsea (Committee member) / Arizona State University (Publisher)
Created2021
Description
This project was completed to understand the evolution of the ability to digest wood in termite symbiotic protists. Lower termites harbor bacterial and protist symbionts which are essential to the termite ability to use wood as a nutritional source, producing glycoside hydrolases to break down the polysaccharides found in lignocellulose. Yet, only a few molecular studies have been done to confirm the protist species responsible for particular enzymes. By mining publicly available and newly generated genomic and transcriptomic data, including three transcriptomes from isolated protist cells, I identify over 200 new glycoside hydrolase sequences and compute the phylogenies of eight glycoside hydrolase families (GHFs) reported to be expressed by termite hindgut protists.
Of those families examined, the results are broadly consistent with Todaka et al. 2010, though none of the GHFs found were expressed in both termite-associated protist and non-termite-associated protist transcriptome data. This suggests that, rather than being inherited from their free-living protist ancestors, GHF genes were acquired by termite protists while within the termite gut, potentially via lateral gene transfer (LGT). For example one family, GHF10, implies a single acquisition of a bacterial xylanase into termite protists. The phylogenies from GHF5 and GHF11 each imply two distinct acquisitions in termite protist ancestors, each from bacteria. In eukaryote-dominated GHFs, GHF7 and GHF45, there are three apparent acquisitions by termite protists. Meanwhile, it appears prior reports of GHF62 in the termite gut may have been misidentified GHF43 sequences. GHF43 was the only GHF found to contain sequences from the protists not found in the termite gut. These findings generally all support the possibility termite-associated protists adapted to a lignocellulosic diet after colonization of the termite hindgut. Nonetheless, the poor resolution of GHF phylogeny and limited termite and protist sampling constrain interpretation.
Of those families examined, the results are broadly consistent with Todaka et al. 2010, though none of the GHFs found were expressed in both termite-associated protist and non-termite-associated protist transcriptome data. This suggests that, rather than being inherited from their free-living protist ancestors, GHF genes were acquired by termite protists while within the termite gut, potentially via lateral gene transfer (LGT). For example one family, GHF10, implies a single acquisition of a bacterial xylanase into termite protists. The phylogenies from GHF5 and GHF11 each imply two distinct acquisitions in termite protist ancestors, each from bacteria. In eukaryote-dominated GHFs, GHF7 and GHF45, there are three apparent acquisitions by termite protists. Meanwhile, it appears prior reports of GHF62 in the termite gut may have been misidentified GHF43 sequences. GHF43 was the only GHF found to contain sequences from the protists not found in the termite gut. These findings generally all support the possibility termite-associated protists adapted to a lignocellulosic diet after colonization of the termite hindgut. Nonetheless, the poor resolution of GHF phylogeny and limited termite and protist sampling constrain interpretation.
ContributorsSanderlin, Viola (Author) / Gile, Gillian H (Thesis advisor) / Wojciechowski, Martin (Committee member) / Weiss, Taylor (Committee member) / Varman, Arul Mozhy (Committee member) / Arizona State University (Publisher)
Created2019