Life Sciences Commons^™

Special Muscles, Annamaria C. Scaccia

Capstones

Special Muscles is a documentary that explores living with Duchenne muscular dystrophy, a fatal degenerative disease that weakens the muscles at an aggressive rate. The film will give an uncensored look at how one family copes with inevitability of the disease and their journey chasing a promising experimental cure.

Special Muscles follows 7-year-old Pietro Scarso and his family as they face the challenges, complications and promise of treating Pietro’s progressive muscle disorder. The film travels from New York to Los Angeles to Philadelphia to document the Scarso family’s race against time as Pietro undergoes a 96-week clinical trial for Eteplirsen, …

Testing The Efficacy Of Lsn2463359, A Metabotropic Glutamate 5 Receptor Positive Allosteric Modulator, In Animal Models Of Schizophrenia, Dierdre M. Freamon

Seton Hall University Dissertations and Theses (ETDs)

For many years the dominant theory surrounding the cause of schizophrenia was focused on elevated dopamine levels found in critical areas of the brain. Recently a new theory has emerged pointing to elevated glutamate levels resulting from hypofunction of NMDA receptors and hypoactivity of GABAergic neurons which normally inhibit glutamatergic cells in a tonic manner. Therefore, while traditional antipsychotics directly block dopamine receptors, some of the newly generated compounds are designed to modulate glutamate to normal levels.

I propose testing the efficacy of the metabotropic glutamate 5 receptor modulator LSN2463359, previously shown to act as an indirect agonist of the …

Rat Hind Limb Nociceptive Withdrawal Response Depends On Initial Paw Position But Not Stimulus Location, Kimberly Seamon

Senior Honors Projects, 2010-2019

There have been numerous studies in non-human animals on the effect of stimulus location on the NWR and at least a few studies that address the role of initial posture. However, all of these studies were conducted in anesthetized, decerebrated, or spinalized mammals. Since descending modulation and long loop reflexes may influence the NWR, the anesthetized spinalized/decerebrated animal may not be an adequate model of normal animals. Therefore, the primary aim of this study was to determine the effect of the stimulus location and initial paw position on the direction and magnitude of the nociceptive withdrawal response to heat stimulus …

Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and second most common neurodegenerative disorder. PD is characterized by the selective loss of dopaminergic neurons and dopamine neurotransmitter within the substantia nigra and termini in the striatum. Progressive loss of dopaminergic neurons occurs over many years in PD, and by the time movement disorder symptoms manifest, up to 50-70% of dopaminergic neurons have been lost. Several aspects of PD pathology have been described in detail, but a better understanding of PD progression is needed to develop more efficient treatments.

Motor symptoms associated with PD do not manifest until significant …

Development Of Manganese-Enhanced Magnetic Resonance Imaging (Memri) Methods To Study Pathophysiology Underlying Neurodegenerative Diseases In Murine Models, Aditya N. Bade

Theses & Dissertations

Manganese-enhanced magnetic resonance imaging (MEMRI) opens the great opportunity to study complex paradigms of central nervous system (CNS) in freely behaving animals and reveals new pathophysiological information that might be otherwise difficult to gain. Due to advantageous chemical and biological properties of manganese (Mn²⁺), MEMRI has been successfully applied in the studies of several neurological diseases using translational animal models to assess comprehensive information about neuronal activity, morphology, neuronal tracts, and rate of axonal transport. Although previous studies highlight the potential of MEMRI for brain imaging, the limitations concerning the use of Mn²⁺ in living animals and …

The Temporal Nature Of The Acute Stress Response And Its Impact On Explicit Learning, Steven B. Hutchinson

Electronic Theses and Dissertations

Acute stress is commonly experienced by many throughout their lives. Given the demanding lifestyle of many career paths, it's important to gauge the influence of these stressors upon cognitive performance. The present dissertation focus' upon explicit learning in attempts to explore one avenue of the stress-cognition relationship. The Trier Social Stress Test (TSST) was used as a lab stressor for Experiments 1 and 2, in which participants are asked to give a speech and complete a difficult math task in front of 2 evaluators trained to monitor non-verbal behavior. Experiment 1 investigates the dynamic stress response during the minutes following …

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Genes And Gene Networks Related To Age-Associated Learning Impairments, Raihan Uddin

Electronic Thesis and Dissertation Repository

The incidence of cognitive impairments, including age-associated spatial learning impairment (ASLI), has risen dramatically in past decades due to increasing human longevity. To better understand the genes and gene networks involved in ASLI, data from a number of past gene expression microarray studies in rats are integrated and used to perform a meta- and network analysis. Results from the data selection and preprocessing steps show that for effective downstream analysis to take place both batch effects and outlier samples must be properly removed. The meta-analysis undertaken in this research has identified significant differentially expressed genes across both age and ASLI …

Exploring And Training Spatial Reasoning Via Eye Movements: Implications On Performance, Victoria A. Roach

Electronic Thesis and Dissertation Repository

This dissertation sought to determine if eye movements could serve as an indicator of success in spatial reasoning, and if eye movements associated with successful completion could be applied to strategically improve spatial reasoning.

Using the line images of Shepard and Metzler, an electronic test of mental rotations ability (EMRT) was designed. Two versions of the test were created, allowing for both a timed (6 seconds per question) and untimed testing environment. Four experiments were designed and completed to relate mental rotation ability (MRA) scores from the EMRT, to patterns in chrononumeric and visual salience data. In each experiment, participants …

Functionally Distinct Pools Of Calcineurin Contribute To Depotentiation-Like Synaptic Changes In The Lateral Amygdala During Auditory Fear Extinction, Elena Kay Rotondo

Theses and Dissertations

Until recently, auditory fear extinction was not thought to modify substrates involved in the storage of the original auditory fear memory. Evidence now suggests that extinction results in the reversal of the fear conditioning-induced potentiation of thalamic inputs to the lateral amygdala. However, little is known about the molecular mechanisms that support this depotentiation of synaptic strength. Here we present behavioral and molecular evidence in support of the contribution of two distinct pools of the protein phosphatase calcineurin to depotentiation-like changes in lateral amygdala AMPA receptor trafficking during auditory fear extinction. Calcineurin protein that exists prior to the onset of …

Disentangling Embodied Cognition: An Examination Of The State, Problems, And Possibilities Of Embodied Cognition, Cody Cash

Graduate Theses and Dissertations

Embodied cognition has received a fair amount of attention in philosophical, neuroscientific, and robotic research during the past several decades, yet the precise nature of its goals, methods, and claims are unclear. This dissertation will ascertain and examine the primary themes in the field of embodied cognition as well as why, and if, they offer significant challenges to traditional cognitive science models. Though many theories believe they are providing accounts that should replace traditional models, to do so they will have to overcome the very difficult challenge of arguing that mental content and capabilities derived from sensorimotor activity can continue …

Neural Mechanisms Supporting Differential Auditory Fear Conditioning, Nicole Christine Ferrara

Theses and Dissertations

Pavlovian fear conditioning provides an ideal way to study memory formation, retention, and updating. Plasticity in the auditory thalamus is required during the acquisition and consolidation of a fear memory when a tone signals a foot shock. The medial geniculate nucleus (MgN) of the auditory thalamus sends projections to the amygdala and auditory cortex and is functionally divided into two different regions, the medial division (MGm) and the ventral division (MGv). Traditionally, these divisions are thought to relay auditory information to the amygdala during fear-related associative learning. However, recent research has suggested a more complex role for the MgN when …

Effects Of Global Dna Methylation Changes On Neurobehavior In Zebrafish, Matthew Christopher Pickens

Theses and Dissertations

A number of environmental neurotoxicants modulate DNA methylation, but its influence on neurobehavior remains unclear. The laboratory has established that low-level developmental methylmercury exposure induces neurobehavioral deficits; the current results demonstrate that it also induces global DNA hypomethylation. DNA methyltransferase 1-mutant zebrafish (exhibit ~70% reduction in enzymatic activity) were used to assess the role of DNA hypomethylation on behavior. Several neurobehavioral assays including the C-start escape, circadian rhythm, basic locomotion and visual-motor response (VMR) were also performed. There was a significant difference in VMR between the wild type and mutant animals. Other behavior assays revealed no significant difference, primarily due …

The Human Intruder Test: An Anxiety Assessment In Rhesus Macaques (Macaca Mulatta), Emily J. Peterson

Masters Theses

The human intruder test (HIT) is a noninvasive tool widely used for assessing anxiety in rhesus macaques (Macaca mulatta). This thesis explores the HIT procedure and applies it to a population of monkeys with a self-injurious behavioral pathology. Individual variation on this test can be used to assess anxiety and temperament. The first experiment of this thesis applied two different procedures of the HIT to 17 monkeys at UMass. Monkeys displayed little response to the intruder, and no significant differences were detected for the two procedures. To determine whether these responses were unique to the UMass monkeys, their …

Regulation Of Jak1 And Jak2 Synthesis Through Non-Classical Progestin Receptors, Hillary Adams

Masters Theses

The anteroventral periventricular (AVPV) nucleus of the hypothalamus integrates estradiol (E₂) and progesterone (P₄) feedback signals from the ovaries to stimulate gonadotropin releasing hormone (GnRH) neurons and trigger an ovulatory surge in luteinizing hormone (LH). E₂ maintains the daily cyclic LH surge and P₄ quickly amplifies the surge and limits it to one day. P₄ amplification of the surge and rapid signaling in the AVPV may occur through its non-classical progestin receptors. Previous in vitro studies using a microarray analysis with N42 mouse embryonic hypothalamic neurons suggest that progesterone membrane component 1 (Pgrmc1) …

Seasonality Of The Stress Response In House Sparrows (Passer Domesticus)., Michael R. Hasstedt

Electronic Thesis and Dissertation Repository

Seasonal changes in plasma corticosterone (CORT) levels indicate that birds modify their stress response through the year. Although this has been well documented, the method by which birds achieve this seasonality is not well understood. In this study I used house sparrows to determine if changes in glucocorticoid receptor (GR) immunoreactivity in several stress-related brain nuclei showed seasonal variation. The house sparrowsshowed seasonal variation in their stress response with baseline CORT levels being highest during the breeding season and lowest during winter. There was also significant change in plasma CORT post-dexamethasone during breeding, but not during other times of the …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

Developmental Stress And The Effects On Physiological And Cognitive-Behavioural Traits In European Starlings, Tara M. Farrell

Electronic Thesis and Dissertation Repository

Birdsong is a complex, learned vocalization that is a phenotypic expression of male quality. The developmental stress hypothesis describes how the cost to possessing a high quality song is paid in early development. Stressful early-life experiences have adverse effects on the development of the neural circuitry that regulates song learning and production, which results in a male advertising with a low quality song in adulthood. The purpose of this thesis was to test the developmental stress hypothesis in several respects in European starlings (Sturnus vulgaris). My objectives were to assess the long-term effects of developmental stress on (1) …

Behavioral, Neurobiological, And Genetic Analysis Of The Circadian Mutant Duper, Emily Nicole Corbett Manoogian

Doctoral Dissertations

The recently discovered circadian mutant hamster duper has a short period of ~23 hours and exhibits exaggerated phase shifts in response to a 15-min light pulse. To increase the understanding of the duper mutation, I performed behavioral, neurobiological, and genetic experiments. Behavioral studies using photic and non-photic stimuli found that large phase shifts exhibited by duper hamsters are specific to photic cues, but not to phase. Additionally, 2/3 of duper hamsters, but no WTs, displayed transient ultradian wheel-running patterns when transferred from light to dark at CT 18. This suggests that the mutation may weaken coupling among components of the …

Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells, Amanda M. Hussey

Doctoral Dissertations

Proper detection is the key to studying any processes on the cellular scale. Nowhere is this more evident than in the tight space which confines the synaptic cleft. Being able to ascertain the location of receptors on live neurons is fundamental to our understanding of not only how these receptors interact and move inside the cell but also how neurons function. Most detection methods rely on significantly altering the receptor; both tagging with a fluorescent protein or targeting the receptor by a fluorescent reporter in the form of a small molecule causes significant difficulties. These localization techniques often result in …

Behavioral And Neural Mechanisms Of Impulsive Choice, Jesse Mcclure

Doctoral Dissertations

Impulsive choice is defined as the preference for a small immediate reward over a larger delayed reward. Individual variablity in impulsive choice correlates with many socially relevant behaviors. Although forms of impulsive choice have been studied in both behavioral ecology and psychology, the exchange of knowledge between these fields is just beginning. Drawing from both of these fields will improve our research methods allowing for a more detailed understanding of this complex behavior. Existing tasks to measure impulsive choice conflate the delay and quantity of the reward. To address this, I have drawn from foraging research to establish a method …

Non-Canonical Activation Of Nrf2 By Dimercaptopropanol As A Treatment For Huntington's Disease, Margaret Lauren Tindale

Electronic Thesis and Dissertation Repository

Mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels are strongly implicated in various neurodegenerative disorders, including Huntington’s disease (HD). Expression of the mutant Huntingtin protein (mHTT) containing an expanded polyglutamine repeat is associated with oxidative stress and toxicity in striatal neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for regulating expression of a diverse array of antioxidant and cytoprotective genes. Most known Nrf2-activating compounds act through the canonical pathway by mimicking a transient oxidative insult, and treatment effects are short-lived. This study reveals an increase in striatal cell viability, and a reduction in …

Mechanisms Of Neuroprotection Against Ischemic Insult By Stress-Inducible Phosphoprotein-1, Jason Xu

Electronic Thesis and Dissertation Repository

Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrP^C) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrP^C, α7nAChR, and ALK2 prior to oxygen-glucose deprivation …

Deep Brain Stimulation And Its Effects On Parkinson Disease Spatiotemporal Gait Parameters., Greydon Gilmore

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) alleviates common appendicular PD symptoms, such as: tremor, rigidity and bradykinesia. However, the effect STN-DBS has on modulating axial gait features has not been properly quantified objectively. The purpose of the present thesis was to investigate the role STN-DBS plays in modulating specific gait features such as pace, asymmetry, variability, rhythm and postural control. It is hypothesized that axial gait function is regulated predominantly by non-dopaminergic control systems. In the acute immediate post-operative phase a surgical effect, named the microlesion effect (MLE), is thought to produce a transient improvement of appendicular and axial symptoms. …

The Effects Of Modafinil And Atomoxetine On Dopamine Signaling In The Striatal Subregions Of The Rat, Martin Bobak

Theses and Dissertations

In an effort to combat diseases and disorders that impede our health, comfort and well-being, an abundance of prescription drugs have emerged in the past 60 years. Many prescription drugs have remarkable efficacy for treating the primary symptoms of these diseases and disorders; however, some drugs carry negative side effects that impose their own adverse symptoms, albeit, often to a lesser degree than the primary symptoms. Thus, one of the main objectives of the pharmaceutical industry is to innovate and develop novel therapeutics, which remediate the primary symptoms of disease and lack undesirable negative side effects. However, in order to …

Laminar Fmri In Auditory Cortex At 7t, Jacob Jl Matthews

Electronic Thesis and Dissertation Repository

Auditory cortex is involved in the perception, attention, memory and imagery of sounds. Neuroimaging has been a rich source of information on which cortical areas are recruited for different tasks. However, a more detailed understanding has been confined to animal studies using invasive imaging modalities, and high-resolution functional descriptions of auditory cortex, including columnar/laminar specific activity, topographical organization within layers, and the way these representations transfer between processing structures remain poorly understood in humans. We present 7T fMRI as a non-invasive tool for high-resolution functional imaging of human auditory cortex on the laminar scale. We describe MATLAB tools for optimizing …

Determining Attention Deficits In Mouse Models Of Alzheimer’S Disease Using Touchscreen Systems, Talal Masood

Electronic Thesis and Dissertation Repository

Behavioural testing in mouse models of Alzheimer’s disease (AD) suffers from lack of standardization and reproducibility issues between laboratories. In order to solve this, a touchscreen system has been developed for mice based on the CANTAB. There are several cognitive dysfunctions that occur due to AD, including deficits in attention that can be tested using the touchscreens. In this study, we tested two mouse models of familial AD (5xFAD and 3xTG) with mutations that lead to an accelerated rate of amyloidosis. Both male and female mice were tested at two separate locations in order to test for the reproducibility of …

Structure-Function Relationship Of The Brain: A Comparison Between The 2d Classical Ising Model And The Generalized Ising Model, Pubuditha M. Abeyasinghe

Electronic Thesis and Dissertation Repository

There is evidence that the functional patterns of the brain observed at rest using fMRI are sustained by a structural architecture of axonal fiber bundles. As neuroimaging techniques advance with time, the relationship between structure and function has become the object of many studies in neuroscience. As recently suggested, the well defined connectivity structure found in the brain can be used to understand the self organization of the brain at rest, as well as to infer the functional connectivity patterns of the brain using different models, such as the Kuramoto model which studies synchronization, and the 2-dimensional classical Ising model, …

Neurobiology Of Seasonal Life-History Transitions, Ashley Rae Lucas

Dissertations and Theses

Many animals exhibit seasonal changes in life-history stages, and these seasonal transitions are often accompanied by dramatic switches in behavior. While the neuroendocrine mechanisms that regulate such behavioral transitions are poorly understood, arginine vasotocin (AVT) and neuropeptide Y (NPY) are excellent candidates because they regulate reproductive and feeding behavior, respectively. In this study, I asked if seasonal changes in AVT and/or NPY are concomitant with spring migration away from the breeding grounds, as male and female red-sided garter snakes (Thamnophis sirtalis parietalis) are transitioning from reproductive to non-reproductive behavior during this time. To address this question, I collected …

Neural And Behavioural Responses To Rewards And Losses In Early Development: A Functional Magnetic Resonance Imaging Study, Niki Hosseini-Kamkar

Electronic Thesis and Dissertation Repository

Functional magnetic resonance imaging (fMRI) was used to investigate the neural and behavioural correlates of learning from rewards and losses in children. Greater blood-oxygen-level dependent (BOLD) responses in the ventral striatum (VS) and the ventromedial prefrontal cortex (VMPFC) were found when participants received rewards compared to when they missed out on an opportunity to receive rewards. In contrast, greater BOLD responses in the anterior insula (AI) and the anterior cingulate cortex (ACC) were found when participants received losses compared to when they avoided losing. The BOLD response to rewards in the VS and VMPFC correlated positively with the tendency to …