Neuroscience and Neurobiology Commons^™

Ros Regulation Of Axonal Mitochondrial Transport, Pin-Chao Liao

Open Access Dissertations

Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using primaryDrosophila neuronal cell culture and the third instar larval nervous system as in vitro and in vivo models, respectively, we studied mitochondrial transport under oxidative stress conditions. In vitro …

Characterizing The Effects Of Repetitive Head Trauma In Female Soccer Athletes For Prevention Of Mild Traumatic Brain Injury, Diana Otero Svaldi

Open Access Dissertations

As participation in women’s soccer continues to grow and the longevity of female athletes’ careers continues to increase, prevention of mTBI in women’s soccer has become a major concern for female athletes as the long-term risks associated with a history of mTBI are well documented. Among women’s sports, soccer exhibits the highest concussion rates, on par with those of men’s football at the collegiate level. Head impact monitoring technology has revealed that “concussive hits” occurring directly before symptomatic injury are not predictive of mTBI, suggesting that the cumulative effect of repetitive head impacts experienced by collision sport athletes should be …

The Effect Of Voluntary Binge Caffeine And Ethanol Coexposure On Neurobehavioral Sensitivity To Cocaine In Male C57bl/6j Mice, Brandon M. Fritz

Open Access Dissertations

Recently, the co-consumption of highly caffeinated energy drinks and alcohol has become a public health concern. Consumption of these beverages has been linked to a wide variety negative consequences including alcohol poisoning, driving under the influence, physical harm, and sexual violence. The more protracted consequences of caffeinated alcohol consumption have received very little attention, however. Some evidence suggests that individuals that frequently consume energy drinks mixed with alcohol are more likely to develop an alcohol use disorder. Interestingly, both caffeine and alcohol use alone have been linked to polydrug abuse. It is therefore of interest whether combined caffeine and alcohol …

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …

Characterization Of Cu-Rich Aggregates In Neurogenic Niches Of The Rodent Brain By X-Ray Fluorescence Microscopy, Brendan T. Sullivan

Open Access Dissertations

Copper is an essential element in the brain playing several critical roles ranging from neurotransmitter synthesis to ATP production. As Cu is typically present in micromolar concentrations and has a spatially capricious distribution in the brain, determining concentrations has historically been challenging. X-ray fluorescence microscopy (XRF) offers excellent spatial resolution (down to 30~nm) and detection limits (sub parts per million), making it an excellent tool for analyzing metal distributions in the brain. Using XRF, it is demonstrated that Cu-rich aggregates with concentrations in the hundreds of millimolar are present in the subventricular zone of rats and mice. As the subventricular …

Optimizing The Neural Response To Electrical Stimulation And Exploring New Applications Of Neurostimulation, Kurt Yuqin Qing

Open Access Dissertations

Electrical stimulation has been successful in treating patients who suffer from neurologic and neuropsychiatric disorders that are resistant to standard treatments. For deep brain stimulation (DBS), its official approved use has been limited to mainly motor disorders, such as Parkinson's disease and essential tremor. Alcohol use disorder, and addictive disorders in general, is a prevalent condition that is difficult to treat long-term. To determine whether DBS can reduce alcohol drinking in animals, voluntary alcohol consumption of alcohol-preferring rats before, during, and after stimulation of the nucleus accumbens shell were compared. Intake levels in the low stimulus intensity group (n=3, 100&mgr;A …

The Pathological Role Of Acrolein In Experimental Autoimmune Encephalomyelitis And Multiple Sclerosis, Melissa A. Tully

Open Access Dissertations

Multiple sclerosis (MS) is an autoimmune demyelinating neuropathy that affects nearly 2.5 million people worldwide. Despite substantial efforts, few treatments are currently available largely due to limited knowledge of pathogenic mechanisms underlying the disease. The immune-inflammatory nature of the pathology has prompted investigation of the role of oxidative stress in disease development and progression; however targeting reactive oxygen species for neutralization has had marginal success therapeutically, suggesting that an alternate oxidative stress-related target would prove beneficial. Recently, our lab has implicated acrolein, a highly reactive aldehyde that is both a byproduct and catalyst of lipid peroxidation, as a potential therapeutic …

Elucidation Of Pharmacologically Manipulated Responding In The Delay Discounting Task In High Alcohol Preferring Mice, Meredith Halcomb

Open Access Dissertations

Impulsive behavior is the hallmark of many psychopathologies. Uncovering the neurobiological mechanisms driving impulsivity is paramount in the development of through the delay discounting (DD) task in both human and animal models. The present study is an examination of the predictive validity of the two primary types of DD procedures in animals, the Adjusting Amounts (AA) and within session Increasing Delays (ID) tasks. Methods:Subjects were administered either1.25 mg/kg d-amphetamine (AMP), 1.5 g/kg ethanol (EtOH) or saline and tested in either the AA or ID method for 15 days to evaluate drug effects on impulsive behavior. Results: Stimulant administration resulted …

Acrolein As A Novel Therapeutic Target For Spinal Cord Injury Induced Neuropathic Pain, Jonghyuck Park

Open Access Dissertations

Despite years of research, post-spinal cord injury (SCI) chronic neuropathic pain remains refractory to treatment and drastically impairs quality of life for SCI victims beyond paralysis. Although inflammation and free radicals contribute to neuropathic pain in SCI, the mechanism is not completely clear. We have recently demonstrated that acrolein, a product and catalyst of lipid peroxidation, induces a vicious cycle of oxidative stress, amplifying its effects and perpetuating oxidative stress and inflammation. In the current study, we have confirmed that acrolein is elevated significantly at least two weeks post-SCI which coincides with the emergence of hyperalgesia (mechanical, cold and thermal). …

Nano-Engineered Polymers In Drug Delivery: Potential Approaches For Attenuation Of Secondary Injury After Spinal Cord Trauma, Wen Gao

Open Access Dissertations

Secondary injury elicits a complex series of pathophysiological events after the primary spinal cord trauma and even after its implantation treatment for neural functional recovery. These secondary injuries include an up-regulation of glial cells associated reactive oxygen species, nitrogen species, and reactive astrogliosis, and they can result in various levels of cellular and tissue damage. The inhibition of them has been proved to lead to functional recovery of the spinal cord. In this study, we concentrated on developing polymers and nano-techniques based drug delivery strategies to eliminate these secondary injuries. ^ To maintain and improve the performance of the implants …

Quantitative Modeling Of Spatiotemporal Systems: Simulation Of Biological Systems And Analysis Of Error Metric Effects On Model Fitting, James Hengenius

Open Access Dissertations

Understanding the biophysical processes underlying biological and biotechnological processes is a prerequisite for therapeutic treatments and technological innovation. With the exponential growth of computational processing speed, experimental findings in these fields have been complemented by dynamic simulations of developmental signaling and genetic interactions. Models provide means to evaluate "emergent" properties of systems sometimes inaccessible by reductionist approaches, making them test beds for biological inference and technological refinement.^ The complexity and interconnectedness of biological processes pose special challenges to modelers; biological models typically possess a large number of unknown parameters relative to their counterparts in other physical sciences. Estimating these parameter …

Morphometric Characterization Of Individual Sympathetic Postganglionic Axons Innervating The Muscle Layers Of The Gastrointestinal Tract Of The Rat: A Complex Effector Model, Gary C. Walter

Open Access Dissertations

A full description of the terminal morphology of sympathetic postganglionic axons innervating the musculature of the gastrointestinal (GI) tract has not been available. Furthermore, common assumptions about the morphology and distribution of catecholaminergic terminal fields have been strongly shaped by the limitations of the techniques employed to distinguish the fibers and complicated by inconsistent findings generated with various methodologies. Thus, the present experiment used modern neural tracer techniques to provide high-resolution labeling of sympathetic fibers projecting to the smooth muscle wall of the GI tract. Fischer 344 rats (N = 50) received injections of dextran biotin into the left …

Smooth Muscle-Specific Removal Of Brain-Derived Neurotrophic Factor Results In Increased Vagal Afferent Innervation To The Intestine And Increased Satiation In Mice, Jessica Erin Biddinger

Open Access Dissertations

Vagal afferents transmit signals regarding food-derived stimuli in the gastrointestinal (GI) tract to the brain. Vagal mechanoreceptors called intraganglionic laminar endings (IGLEs) innervate the smooth muscle wall of GI organs and detect stretch and tension to regulate GI reflexes and satiation. Brain-derived neurotrophic factor (BDNF) is expressed in the smooth muscle of developing GI organs when vagal afferents from the nodose ganglion begin to innervate the GI tract. Therefore, it was hypothesized BDNF is necessary for development of vagal afferents that innervate this tissue. Targeted smooth muscle-specific BDNF homozygous knockout (BDNF SM -/-) mice were generated and .vagal afferent innervation …

Effects Of Hearing Aid Amplification On Robust Neural Coding Of Speech, Jonathan Daniel Boley

Open Access Dissertations

Hearing aids are able to restore some hearing abilities for people with auditory impairments, but background noise remains a significant problem. Unfortunately, we know very little about how speech is encoded in the auditory system, particularly in impaired systems with prosthetic amplifiers. There is growing evidence that relative timing in the neural signals (known as spatiotemporal coding) is important for speech perception, but there is little research that relates spatiotemporal coding and hearing aid amplification.

This research uses a combination of computational modeling and physiological experiments to characterize how hearing aids affect vowel coding in noise at the level of …

Reasoning Across Language And Vision In Machines And Humans, Andrei Barbu

Open Access Dissertations

Humans not only outperform AI and computer-vision systems, but use an unknown computational mechanism to perform tasks for which no suitable approaches exist. I present work investigating both novel tasks and how humans approach them in the context of computer vision and linguistics. I demonstrate a system which, like children, acquires high-level linguistic knowledge about the world. Robots learn to play physically-instantiated board games and use that knowledge to engage in physical play. To further integrate language and vision I develop an approach which produces rich sentential descriptions of events depicted in videos. I then show how to simultaneously detect …

Effects Of Dip-Coated Films On The Properties Of Implantable Intracortical Microelectrodes, Salah Sommakia

Open Access Dissertations

The successful clinical use of implantable intracortical microelectrodes (ICMs) to treat certain types of deafness, blindness, and paralysis is limited by a reactive tissue response (RTR) of the brain. This RTR culminates in the formation of a tight glial scar and a loss of neuronal density around implanted ICMs, and is accompanied by a decrease in signal to noise ratio and an increase in impedance. While no comprehensive mechanistic understanding of the underlying biology is currently agreed upon in the field, a general consensus exists around a highly volatile acute RTR phase. During this acute phase, the electrical properties of …

The Structure Of Consciousness, Lowell Keith Friesen

Open Access Dissertations

In this dissertation, I examine the nature and structure of consciousness. Conscious experience is often said to be phenomenally unified, and subjects of consciousness are often self-conscious. I ask whether these features necessarily accompany conscious experience. Is it necessarily the case, for instance, that all of a conscious subject's experiences at a time are phenomenally unified? And is it necessarily the case that subjects of consciousness are self-conscious whenever they are conscious? I argue that the answer to the former is affirmative and the latter negative.

In the first chapter, I set the stage by distinguishing phenomenal unity from other …

Neuroprotection By Chitosan And Chitosan Nanoparticles, Bojun Chen

Open Access Dissertations

In the U.S., about 200,000 people are currently living with spinal cord injury (SCI). An estimated of 50%-70% of all SCI cases occurs in the range of ages between 15-35 years old. The destructive neurotrauma results in the majority of adult disability, even after patients suffering with SCI survived from the acute death. There are two stages involved in the progression of SCI, the primary stage and the secondary stage. The primary stage is mainly the mechanical damage to the central nervous system. The rapid collapse of the integrity of cell membrane and tissue is often one of the initial …

Novel Progestin Signaling Molecules In The Brain: Distribution, Regulation And Molecular Mechanism Of Action, Karlie A. Intlekofer

Open Access Dissertations

Progesterone regulates female reproduction in many ways, yet it is still unclear how signals are conveyed through nuclear and extranuclear receptors. The traditional notion was that progesterone binds classical progesterone receptors to alter gene transcription. This view has been challenged by the discovery of additional progesterone signaling molecules important for progesterone actions in non-neural cells. In granulosa cells, the progesterone receptor membrane component 1 (Pgrmc1) mediates progesterone effects by forming a receptor complex with binding partner, Serpine mRNA binding protein 1, but it is unknown whether these molecules function similarly in the brain. To begin to address these issues, I …

Examining The Development Of Handedness In Rhesus Monkey And Human Infants Using Behavioral And Kinematic Measures, Eliza Lynn Nelson

Open Access Dissertations

Handedness is a widely studied behavioral asymmetry that is commonly measured as a preference for using one hand over the other. Right hand preference in humans occurs at a ratio of 9:1, whereas left hand preference in rhesus monkeys has been estimated at 2:1. Despite differences in the direction and degree of hand preference, this dissertation investigated whether primates share common underlying factors for the development of handedness. Previous work in human infants has identified a predictive relationship between rightward supine head orientation and later right hand preference. Experiment 1 examined the relationship between neonatal head orientation and later hand …

Investigations Into The Potential For 3,4-Methylenedioxymethamphetamine To Induce Neurotoxic Terminal Damage To Serotonergic Neurons, Dominik Biezonski

Open Access Dissertations

High doses of 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") are known to reduce levels of various serotonergic markers outside of the raphe nuclei. To test the hypothesis that these deficits reflect a degeneration of distal axons/terminals, we investigated the effects of an MDMA binge (10mg/kg x 4) on the relative protein and genetic expression of several serotonergic markers in rats, as well as the effects of this compound on the quantity of serotonergic terminals in these animals. In experiment I, we examined whether MDMA alters serotonin transporter (SERT) levels as determined by lysate binding and immunoblotting analyses. Both methods of analysis revealed MDMA-induced …

Early Rearing Experience, Hypothalamic-Pituitary-Adrenal (Hpa) Activity, And Serotonin Transporter Genotype: Influences On The Development Of Anxiety In Infant Rhesus Monkeys (Macaca Mulatta), Amanda Dettmer

Open Access Dissertations

A gene x environment interaction exists in the expression of anxiety for both human and nonhuman primates, such that individuals who are carriers of the (s) allele of the serotonin transporter genotype ( 5-HTT LPR) and exposed to early life stress are more at risk for exhibiting anxiety. The hypothalamic-pituitary-adrenal (HPA) axis has also been implicated in anxiety disorders but the relationship between early life/genotype, HPA activity, and anxiety is not well understood. Further, studies linking the HPA axis to anxiety have relied on "point" samples (blood and salivary cortisol) which reflect moments in time rather than long-term activity. The …

Visuospatial Reasoning In Toddlers: A Correlational Study Of Door Task Performance, Iris Louella Price

Open Access Dissertations

Previous research using violation-of-expectation paradigms suggests that very young infants have a good understanding of unobserved physical events. Yet toddlers appear to lack this knowledge when confronted with the door task, a visuospatial reasoning task which parallels ones used in the habituation/looking time studies. Many studies have been conducted in an effort to determine why toddlers perform poorly on the door task yet the answer remains unclear. The current study used a correlational approach to investigate door task performance from both psychological (executive function), and neuroscience (prefrontal cortex) perspectives. Children between the ages of 2 ½ - 3 years were …