Life Sciences Commons^™

The Processing Of Amyloid Precursor Protein In The Central Nervous System Of Humans And Rhesus Macaques, Justyna Anna Dobrowolska

All Theses and Dissertations (ETDs)

Alzheimer's disease: AD) is the most common dementia, currently afflicting 30 million people worldwide, with prevalence steadily increasing. Over 99% of AD cases are classified as sporadic, in which the major risk factors are age: greater than 65 years) and the ApoE-ε4 allele: in a gene dose dependent manner). The minority of AD cases: less than 1%) are caused by autosomal dominant inheritance of a genetic mutation in one of three genes: Amyloid Precursor Protein: APP), Presenilin-1: PSEN1), or Presenilin-2: PSEN2). Mutation carriers will generally notice cognitive decline starting at a relatively young age, anytime between their 30s-50s, and eventually …

The Effects Of Chronic Simvastatin Treatment On The Expression Of Behavioral Symptoms In A Transgenic Mouse Model Of Huntington’S Disease, Ashley Whitmarsh

University of New Orleans Theses and Dissertations

Huntington’s disease (HD) is a heritable, neurodegenerative disorder characterized by motor, cognitive, and psychiatric disturbances. An unstable CAG expansion within the gene normally encoding for the Huntingtin protein is responsible. The expanded mutant form of Huntingtin and the putative protein co-factor Rhes interact and cause cell death within the striatum. We hypothesized chronic treatment with simvastatin, a cholesterol lowering drug, would disrupt the biosynthetical pathway which gives both Rhes and its target cells binding sites and render Rhes inactive. Healthy and HD mice were treated with simvastatin or a vehicle. Animals’ motor behavior was assessed with three separate tests over …

Reaching For The Light: The Prioritization Of Conspicuous Visual Stimuli For Reflexive Target-Directed Reaching, Daniel K. Wood

Electronic Thesis and Dissertation Repository

The degree to which something stands out against the background of its environment communicates important information. The phenomenon of camouflage is a testament of the degree to which visual salience and probability of survival tend to overlap. Salient stimuli often elicit fast, reflexive movements in order to catch prey or avoid a predator. The overarching goal of the work presented in this thesis is to investigate how the physical salience of visual stimuli influence the programming and execution of reaching movements. I approached this question by recording kinematics and muscle responses during reaching movements. Broadly, this thesis investigates the effect …

The Hippocampus Participates In A Pharmacological Rat Model Of Absence Seizures, Justin Andrew Arcaro

Electronic Thesis and Dissertation Repository

The thalamocortical network is responsible for the generation of spike-and-wave discharges (SWDs) in absence epilepsy. Recent studies suggest a potential involvement of the hippocampus, which may explain the variability in the extent of cognitive deficits among patients with absence epilepsy. I hypothesize that the hippocampus may become entrained in spike-and-wave discharges following thalamocortical activation. The gamma-butyrolactone (GBL) rat model of absence seizures was used in this thesis. Following GBL injection, SWDs of 4 to 6 Hz developed in the spontaneous local field potentials (LFPs) recorded by depth electrodes in the thalamus, neocortex and hippocampus. Synchronization of hippocampal, thalamic and neocortical …

Contribution Of Trpm2 To Memory Loss In An Alzheimer's Mouse Model, Megan M. Chen

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the progressive deterioration of memory and other intellectual abilities. Accumulation of amyloid-β (Aβ) peptide, the major contributor to the senile plaques central to AD, is thought to mediate neurotoxicity by inducing oxidative stress and calcium dysregulation. Transient Receptor Potential Melastatin type 2 (TRPM2) is a calcium permeable, non-selective cation channel activated under oxidative stress and ultimately induces cell death. The APPSWE/PSEN1ΔE9 double transgenic mouse model carries the human APPswe (Swedish mutations K594N/M595L) and PS1 mutations with a deletion in exon 9 (PS1-dE9), and is one of the most commonly used AD …

Neural Responses During Trace Conditioning With Face And Non-Face Stimuli Recorded With Magnetoencephalography, Nicholas Lee Balderston

Theses and Dissertations

During fear conditioning a subject is presented with an initially innocuous stimulus like an image (conditioned stimulus; CS) that predicts an aversive outcome like a mild electric shock (unconditioned stimulus; UCS). Subjects rapidly learn that the CS predicts the UCS, and show autonomic fear responses (CRs) during the presentation of the CS. When the CS and the UCS coterminate, as is the case for delay conditioning, individuals can acquire CRs even if they are unable to predict the occurrence of the UCS. However when there is a temporal gap between the CS and the UCS, CR expression is typically dependent …

The Role Of The Amygdala, Retrosplenial Cortex, And Medial Prefrontal Cortex In Trace Fear Extinction And Reconsolidation, Janine Lynn Kwapis

Theses and Dissertations

A wealth of research has outlined the neural circuits responsible for the consolidation, reconsolidation, and extinction of standard "delay" fear conditioning, in which awareness is not required for learning. Far less is understood about the neural circuit supporting more complex, explicit associations. "Trace" fear conditioning is considered to be a rodent model of explicit fear because it relies on the cortex and hippocampus and requires explicit contingency awareness in humans for successful acquisition. In the current set of studies, we aimed to better characterize the neural circuit supporting the consolidation, reconsolidation, and extinction of trace fear in order to better …

The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki

Theses and Dissertations

Developing neurons extend processes to specific targets and establish connections that are essential for future function of the nervous system. One of these processes, the axon, has a motile tip called a growth cone that rearranges its membrane-associated actin cytoskeleton to turn toward or away from environmental guidance cues. Growth associated protein 43 (GAP-43) is one of the most abundant proteins associated with axonal growth cone membranes and is known to modulate the formation and stability of the actin cytoskeleton during axon guidance. Protein kinase C (PKC)-mediated phosphorylation of GAP-43 on serine 42 regulates its interactions with actin. Phosphorylated GAP-43 …

Mtorc1 Signaling In Memory Formation And Dysfunction, Natalia S. Rozas De O'Laughlin

Dissertations & Theses (Open Access)

The mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway integrates cellular availability of growth factors, energy and amino acids to regulate protein synthesis and autophagy. The mTORC1 pathway has also been shown to be required for memory consolidation, and its dysregulation is associated with many neurological disorders. MTORC1 is negatively regulated by the tuberous sclerosis complex (TSC1/2). When ATP and growth factors are available, TSC1/2 is inhibited and mTORC1 activity can be restored. In a complementary regulatory pathway, amino acids signal to mTORC1 through the Rag GTPases and Ragulator complex, which modulate the translocation of mTORC1 from the cytoplasm to …

Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum

Dissertations & Theses (Open Access)

Understanding speech in face-to-face conversation utilizes the integration of multiple pieces of information, most importantly the auditory vocal sounds and visual lip movements. Prior studies of the neural underpinnings of audiovisual integration in the brain have provided converging evidence to suggest that neurons within the left superior temporal sulcus (STS) provide a critical neural hub for the integration of auditory and visual information in speech. While most studies of audiovisual processing focus on neural mechanisms within healthy, young adults, we currently know very little about how changes to the brain can affect audiovisual integration in speech. To examine this further, …

The Development Of A Traumatic Brain Injury Bioreactor, Zachery Heller

Graduate Theses and Dissertations

Approximately 1.7 million Americans experience a traumatic brain injury (TBI) each year. Concussive injuries are a subset of TBI in which blows to the head cause the brain to collide against the interior of the skull. Damage to the neurons, supporting cells, and surrounding extra cellular matrix resulting from these collisions can lead to permanent physical, cognitive, and psychological impairment. We believe the prevalence and clinical significance of concussive injures warrants research investment. To study brain injury following TBI, in vivo models have been the gold standard for TBI experiments. Although a valuable research alternative, animals are expensive, raise ethical …

Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz

Dissertations & Theses (Open Access)

Plakophilin-3, the less studied member of the plakophilin-catenin subfamily, and the larger catenin family, binds directly to desmosomal cadherin cytoplasmic domains and enhances desmosome formation and stability. In mammals, plakophilin-3 is expressed at the highest levels in desmosome-enriched tissues such as epithelia, with the knock-out in mice producing corresponding reductions in ectodermal integrity. In tissue, cellular and intracellular contexts where plakophilin-3 is not at the desmosomal plaque, little is known about its functions in the cytoplasm or nucleus, where it also localizes.

My work employed embryos of the amphibian, Xenopus laevis, to examine plakophilin-3’s developmental roles. I first evaluated …

Metergoline, The Basolateral Amygdala And The Ventral Pallidum: Implications For Panic Disorder, Douglas Ryan Schuweiler

Theses and Dissertations

Panic disorder (PD) is a common mental illness characterized by recurring spontaneous panic attacks. Scientific investigation into PD has been accelerated by the development of rat models of PD. These models can be validated by responses to intravenous sodium lactate (NaLac), including tachycardia, that are similar to PD patient responses. Previous work on established PD models has suggested that antagonism of serotonin (5-HT) receptors in the basolateral amygdala (BLA) may be sufficient to model PD. To test this hypothesis metergoline (MET), a 5-HT receptor antagonist, or vehicle was microinjected into the BLA of anesthetized rats. Following the microinjection, NaLac or …

An Investigation Into The Presynaptic Actions By Which Amphetamine Activates Dopamine Signaling Within Striatal Subregions Of The Rat., Dan P. Covey

Theses and Dissertations

Despite decades of intense research and a consensus view in the field, the work presented herein provides strong evidence that the primary mechanism of amphetamine action should be re-evaluated. Rather than depleting vesicular dopamine stores and promoting non-exocytotic efflux through the dopamine transporter in vivo, recent evidence demonstrates that amphetamine augments phasic dopamine signaling instead. This signaling modality is critical for reinforcement learning and is dependent on intact vesicular stores. The new findings support over-activation of phasic dopamine signaling as a common mechanism in the addiction process.

Taking Tone Into Account: Cognitive Neuroscientific Investigations Of Mandarin Chinese Spoken Word Processing, Jeffrey G. Malins

Electronic Thesis and Dissertation Repository

To date, theories of how humans recognize spoken words have yet to account for tonal languages such as Mandarin Chinese. One reason for this is that we know relatively little about how native speakers of tonal languages process spoken words in the brain. This dissertation addresses this problem by examining Mandarin spoken word processing in both adult native speakers and typically developing children. In adults, functional magnetic resonance imaging (fMRI) was used to assess the extent to which the brain regions involved in processing tonal information are distinct from those involved in vowel processing (Chapter 2), while event related potentials …

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 …

Investigation Of Sox9 Ablation On Neural Stem Cell Behaviour After Spinal Cord Injury, Stephen Mcdonald

Electronic Thesis and Dissertation Repository

After spinal cord injury neural stem cells are activated to proliferate and differentiate primarily into astrocytes, but are unable to replace lost neurons or aid in neurological recovery. Recent research shows that the transcription factor Sox9 promotes gliogenesis while inhibiting neurogenesis, and that Sox9 ablation causes improved recovery after spinal cord injury. The purpose of this study was to determine how Sox9 ablation alters neural stem cell behaviour after spinal cord injury and whether it leads to neurological improvements. We used BrdU and YFP to label and track neural stem cells and a neural stem cell-specific Sox9 knockout mouse model …

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 …

Neural Circuits Involved In Mental Arithmetic: Evidence From Customized Arithmetic Training, Christian Battista

Electronic Thesis and Dissertation Repository

An arithmetic training study was conducted using a novel paradigm known as Customized Arithmetic Training (CAT). Using the CAT system, self-reports obtained from the participants were used to generate individually tailored problem sets. These problem sets balanced strategy use such that each participant started with an equal amount of problems solved by fact retrieval (e.g., 2 + 2 = 4) and an equal amount of problems solved by procedural calculation (e.g., 34 + 37). Following the training period, participants solved trained and untrained problems from their customized arithmetic sets while undergoing an fMRI scan, after which they again provided self-reported …

Testing The Template Hypothesis Of Vocal Learning In Songbirds., Adriana Diez

Electronic Thesis and Dissertation Repository

The auditory forebrain regions NCM and CMM of songbirds are associated with perception and complex auditory processing. Expression of the immediate-early gene ZENK varies in response to different sounds. Two hypotheses are proposed for this. First, ZENK may reflect access to a representation of song memories. Second, ZENK may reflect attention. I tested these hypotheses by measuring ZENK in response to tutored heterospecific or isolate songs compared to non-tutored wild-type song. Young zebra finch females were exposed to different tutoring conditions and later exposed to different playbacks, and the expression of ZENK in CMM and NCM measured. ZENK responses varied …

Cortical Cannabinoid Modulation Of Subcortical Dopamine Activity: Implications For Emotional Processing, Brittany Draycott

Electronic Thesis and Dissertation Repository

Humans receive countless sensory inputs from the outside world to which they assign a certain level of emotional significance. However, there are times when an individual may assign an abnormally high level of emotional salience to an otherwise non-significant event, resulting in an inappropriate allocation of attention as seen in the hallucinations and psychosis associated with schizophrenia. Several brain regions are involved in this emotional processing, including the medial prefrontal cortex (mPFC) and the ventral tegmental area (VTA). We have previously shown that activation of mPFC cannabinoid (CB1) receptors in rats causes a potentiated fear response to a normally non-salient …

Investigating The Pathological Response To Beta Amyloid Toxicity In Rats: The Role Of Age And The Antioxidant Catalase-Skl, Hayley J. Nell

Electronic Thesis and Dissertation Repository

Accumulation of beta-amyloid (Aβ) in the brain is a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer’s disease (AD). In part, Aβ exerts its toxic effects by increasing reactive oxygen species (ROS) and neuroinflammation in the brain. Aging, a major risk factor for AD is also associated with increased production of ROS. This study investigated the age-related pathological response to Aβ toxicity and examined whether catalase-SKL(CAT-SKL), a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase, is able to reduce Aβ toxicity. Bilateral intracerebroventricular (icv) injections of the Aβ_25-35 peptide was used to model Aβ …

Cognitive Roles Of Anterior And Posterior Pedunculopontine Tegmentum Subregions, Jordan C. Robinson

Electronic Thesis and Dissertation Repository

The pedunculopontine tegmentum (PPT) is part of the mesopontine cholinergic system with distinct anterior and posterior subdivisions. With fast sensory input and descending connections to brainstem locomotor centers, we predict posterior PPT (pPPT) mediates prepulse inhibition of acoustic startle reflex, a form of sensorimotor gating that affects attentional processes. Similar to pPPT cholinergic projections to ventral tegmental area, we predict anterior PPT cholinergic input to substantia nigra regulates dopamine release in striatum, which is important for reinforcement learning. We lesioned the PPT bilaterally in male Sprague Dawley rats with ibotenic acid. Posterior cholinergic cell loss was significantly correlated with prepulse …

A P300 Based Cognitive Assessment Battery For Severely Motor-Impaired And Overtly Non-Responsive Patients, Aaron M. Kirschner

Electronic Thesis and Dissertation Repository

Diagnosing disorders of consciousness (DOC) is notoriously difficult, with estimates of misdiagnosis rates as high as 40%. Moreover, recent studies have demonstrated that patients who do not show signs of volitional motor responses can exhibit preserved command following detected by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although these patients clearly retain some cognitive abilities, lack of consistent motor responses makes administration of standard neuropsychological tests impossible. Consequently, the extent of their cognitive function is unknown. In the current study, we developed and validated a P300b event related potential (ERP) neuropsychological battery in healthy participants to assess components of …

Investigation Of Auditory Encoding And The Use Of Auditory Feedback During Speech Production, Laura E. Beamish

Electronic Thesis and Dissertation Repository

Responses to altered auditory feedback during speech production are highly variable. The extent to which auditory encoding influences this varied use is not well understood. Thirty-nine normal hearing adults completed a first formant (F1) manipulation paradigm where F1 of the vowel /ε/ was shifted upwards in frequency towards an /æ/–like vowel in real-time. Frequency following responses (FFRs) and envelope following responses (EFRs) were used to measure neuronal activity to the same vowels produced by the participant and a prototypical talker. Cochlear tuning, measured by SFOAEs and a psychophysical method, was also recorded. Results showed that average F1 production changed to …

Toxin-Induced Gustatory Conditioning In Rats: Examining The Effects Of Low Dose Toxins In Food On Rat Feeding Behaviour And Avoidance Conditioning, Amber N. Good

Electronic Thesis and Dissertation Repository

Foraging animals must learn which foods in their environment will maximize their nutritional needs but minimize the amount of ingested toxins. These animals rely on the integration of sensory and gustatory information and post-ingestive feedback from the foods they consume. Gustatory conditioning can be studied by using the conditioned taste avoidance paradigm and the toxin LiCl. This thesis first examined the dose related effects of low levels of LiCl on the ingestion of different palatable sucrose and salt solutions. The present findings support the hypothesis that rats use a behavioural tolerance mechanism to regulate their intake of foods containing low …

Functional Analysis Of Corazonin And Its Receptor In Drosophila Melanogaster, Kai Sha

Doctoral Dissertations

Corazonin (Crz) is an amidated undecapeptide originally isolated from the American cockroach. It has been shown to affect diverse physiological functions in a species-specific manner. However, the functionality of Crz in Drosophila melanogaster has not yet been determined. To gain insight into the role of Crz signaling in vivo, Crz and CrzR null alleles were obtained by transposable element mobilization. Flies carrying a deficiency uncovering Crz and pr-set7 loci were generated via P-element excision, and the latter was rescued by wild-type pr-set7 transgene. A mutation of Crz receptor (CrzR) was generated by Minos-element mobilization from …