Neuroscience and Neurobiology Commons^™

Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton

Theses and Dissertations

Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.

Pdz Protein Regulation Of Β-Arrestin Recruitment And Gpcr Trafficking, Sarah Gupta

Electronic Thesis and Dissertation Repository

β-arrestins are versatile adaptor proteins that play a vital role in regulation of G protein coupled receptor (GPCR) trafficking and signalling properties. PDZ proteins have previously been shown to modulate β-arrestin2 recruitment and receptor internalization for many GPCRs including Corticotropin-Releasing Factor Receptor 1 (CRFR1), a receptor whose antagonists have been shown to demonstrate both anxiolytic- and antidepressant-like effects. Further characterization of the interplay between β-arrestins and PDZ proteins may aid in determining a potential mechanism for PDZ protein regulation of GPCR trafficking. Our findings suggest that PDZ proteins PSD-95, MAGI1, and PDZK1 complex with β-arrestin2 by interacting via the PDZ …

Riding The Mind Lightning, William A. Fortuna

Capstones

Neuromodulation is the practice of applying external stimulation, either electric or magnetic, to the human in order to affect positive change. TDCS or transcranial direct current stimulation is a neuromodulatory technique using a 9-volt battery. Because of the simplicity of the device, and it's relatively low potential for harm, the technique is popular with both researchers and at-home enthusiasts. To find out whether this technique works the way some people say it does, I built my own.

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Global Gene Expression Profiling Of Healthy Human Brain And Its Application In Studying Neurological Disorders, Simarjeet K. Negi

Theses & Dissertations

The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed …

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz

Theses & Dissertations

Although the etiology of a particular disease will vary, there are genetic and epigenetic bottlenecks that frequently converge resulting in dysregulation of mitogenic and morphogenetic signaling. This propensity is acutely experienced in malignancy and neurodegenerative disease.

Here, we have first investigated the role of dysregulated signaling in the context of pancreatic cancer (PC). Morphogenetic signaling has been regarded as a pleiotropic pathway with the potential to promote and inhibit metastatic features. Our investigation of bone morphogenetic protein 2 (BMP-2), an archetypical member of the BMP superfamily, has revealed the presence of extracellular, intracellular, and long non-coding RNA products. Our findings …

Motor Control In Individuals With Multiple Sclerosis, David Arpin

Theses & Dissertations

This dissertation explored motor control in individuals with multiple sclerosis (MS) by quantifying the behavioral and neurophysiological deficits present in these individuals. We behaviorally quantified the precision of the ankle plantarflexor musculature of individuals with MS. Our results indicated that the individuals with MS had a greater amount of variability in the precision of the isometric ankle torques, and that this greater variability was related to decreased walking performance. To further explore whether these motor control deficits were due to aberrant cortical activity associated with planning motor actions, we used magnetoencephalography to assess the motor planning and execution stages of …

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 …

Dopamine D1 Receptor Activity In The Basolateral Amygdala Is Important For Mediating Fear, Reward And Safety Discrimination Learning, Ka Ho Ng

Open Access Theses

Post traumatic stress disorder (PTSD) patients frequently show impairment in safety learning (Jovanovic, Kazama, Bachevalier, & Davis, 2012). Since the amygdala is known to be critical for emotional processing(Wassum & Izquierdo, 2015) and dopamine signaling in the amygdala is important for mediating both fear and reward learning, current experiments examined the role of dopamine signaling in the BLA in mediating both safety learning and reward seeking. We manipulated dopamine D1 receptor activity with a D1 receptor agonist (SKF 38393) or D1 receptor antagonist (SCH23390) either systemically or infused directly into the BLA 20 minutes prior to training rats in a …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations & Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Apoaequorin Differentially Modulates Fear Conditioning In Adult And Aged Rats, Vanessa Ehlers

Theses and Dissertations

Normal aging is associated with a number of changes in behavioral and cellular function, and is often linked to increased susceptibility to cognitive impairment. The hippocampus has been widely implicated in learning and memory, and many forms of learning that are hippocampus-dependent (e.g. trace fear conditioning) are impaired in aged animals. A proposed contributor to aging-related cognitive impairment is aging-related calcium (Ca2+) dysregulation. This dysregulation is thought to result from changes in specific Ca2+-regulatory mechanisms, including abnormal Ca2+ ion channel activity or expression, as well as reduced Ca2+-binding protein (CaBP) expression, which is associated with cognitive and synaptic impairment. Previous …

The Effects Of Exercise Pattern And Intensity On The Expression Of Flk-1 And Flt-1 Receptors In The Hippocampus And Cerebellum, Morgan E. Stevenson

Theses and Dissertations

Aerobic exercise benefits the body and brain. In the brain, these benefits include neuroprotection and improved cognition. These exercise-induced changes are attributed in part to angiogenesis: the growth of new capillaries from preexisting vessels. One critical factor involved in the regulation of angiogenesis is VEGF and its receptors Flk-1 and Flt-1. Although exercise is generally found to be beneficial, there are wide variations in the exercise regimens used across experiments. This study standardized some of these variations. In this study, rats were either assigned to a voluntary wheel running or a forced wheel running exercise condition. Within each condition, animals …

Cellular And Genetic Bases Of Cold Nociception And Nociceptive Sensitization In Drosophila Larvae, Heather N. Turner

Dissertations & Theses (Open Access)

Organisms from flies to mammals utilize thermoreceptors to detect and respond to noxious thermal stimuli. Although much is understood about noxious heat avoidance, our understanding of the basic biology of noxious cold perception is gravely minimal. Numerous clinical conditions disrupt the sensory machinery, such as in patients suffering from tissue damage (from wound or sunburn), or injury to the peripheral nerves, as in patients with diabetes or undergoing chemotherapy. Our goal is to determine the genetic basis for noxious cold perception and injury-induced nociceptive sensitization using the genetically tractable Drosophila model. Using a novel "cold probe" tool and assay we …

Transient Receptor Potential Cation Channel, Subfamilies V, Member 1 (Trpv1) And M, Member 1 (Trpm1) Contribute To Neural Signaling In Mouse Retina., Jennifer Noel

Electronic Theses and Dissertations

The retina processes light information through parallel pathways in order to extract and encode the visual scene. Light information is transmitted to the brain through approximately 30 ganglion cells (GCs), the retinal output neurons. Trp channels modulate the responses of retinal neurons within specific pathways. The study of the expression and function of the majority of Trp channels in the retina is largely in its infancy. My dissertation first investigated the expression and function of the transient receptor potential vanilloid-1 (TRPV1) receptor/channel in the retina. TRPV1, the first cloned and most highly studied Trp channel in the peripheral nervous system, …

Effects Of Repeated Aripiprazole Treatment On The Camp And Akt Pathways In The Dorsal Striatum Of Preadolescent And Adult Rats, Megan Leigh Becker

Electronic Theses, Projects, and Dissertations

The positive symptoms of schizophrenia primarily result from an excess of high affinity D2-like receptors (i.e. D2^High receptors). First-generation antipsychotics, such as haloperidol, are D2-like antagonists that can cause severe extrapyramidal effects. Aripiprazole, a dopamine and serotonin partial agonist, has fewer side effects, making it tolerable for adults and children. Extrapyramidal effects (e.g. Parkinsonism, dystonia, and akathisia) are among the most problematic side effects produced by antipsychotic compounds, which likely result from an excess of D2-like receptors in the dorsal striatum. In order to examine the effects of repeated antipsychotic treatment on dopamine system functioning, this thesis compared the …

Exploring The Production Of Extracellular Matrix By Astrocytes In Response To Mimetic Traumatic Brain Injury, Addison Walker

Graduate Theses and Dissertations

Following injury to the central nervous system, extracellular modulations are apparent at

the site of injury, often resulting in a glial scar. Astrocytes are mechanosensitive cells, which can create a neuroinhibitory extracellular environment in response to injury. The aim for this research was to gain a fundamental understanding of the affects a diffuse traumatic brain injury has on the astrocyte extracellular environment after injury. To accomplish this, a bioreactor culturing astrocytes in 3D constructs delivered 150G decelerations with 20% biaxial strain to mimic a traumatic brain injury. Experiments were designed to compare the potential effects of media type, number of …

Maguk Scaffolds Organize A Key Synaptic Complex In Horizontal Cell Processes Contacting Photoreceptors, Alejandro Vila, Ph.D.

Dissertations & Theses (Open Access)

Synaptic processes and plasticity of synapses are mediated by large suites of proteins. In most cases, many of these proteins are tethered together by synaptic scaffold proteins. Scaffold proteins have a large number and typically a variety of protein interaction domains that allow many different proteins to be assembled into functional complexes. As each scaffold protein has a different set of protein interaction domains and a unique set of interacting partners, the presence of synaptic scaffolds can provide insight into the molecular mechanisms that regulate synaptic processes. In studies of rabbit retina, we found SAP102 and Chapsyn110 selectively localized in …

Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi

Theses and Dissertations

Attention deficit hyperactivity disorder (ADHD) is thought to be associated with dysfunction of ascending catecholamine neuronal systems, particularly dopamine (DA) and norepinephrine (NE). Dysfunction of these catecholamine neurons innervating the prefrontal cortex is hypothesized to underlie impaired executive functions. Dysfunction of the DA neurons innervating the striatum is additionally hypothesized to underlie deficits in motivation and reinforcement learning. However, mechanisms of action of therapeutic drugs used for treating ADHD have mainly focused on catecholamines in the prefrontal cortex and have not adequately addressed the role played by DA signaling in the striatum. Stimulants such as Adderall® and Ritalin® are chemically …

The Neural Correlates Of Emotion Reactivity And Regulation In Young Children With Adhd, Claudia I. Lugo-Candelas

Doctoral Dissertations

Attention-deficit hyperactivity disorder (ADHD) is the most frequently occurring pediatric neurobehavioral disorder. Although emotion reactivity and regulation are frequently impaired in ADHD, few studies have examined these factors in preschool aged children with ADHD, and none have explored the neural correlates of emotion reactivity and regulation in this group though event-related potentials (ERPs). Children aged 4 to 7 with (n = 24) and without (n = 30) ADHD symptoms completed an attention task composed of four blocks: baseline, frustration, suppression, and recovery. In the frustration and suppression blocks, negative affect was induced by false negative feedback. During the …

Towards Deeper Understanding In Neuroimaging, Rex Devon Hjelm

Computer Science ETDs

Neuroimaging is a growing domain of research, with advances in machine learning having tremendous potential to expand understanding in neuroscience and improve public health. Deep neural networks have recently and rapidly achieved historic success in numerous domains, and as a consequence have completely redefined the landscape of automated learners, giving promise of significant advances in numerous domains of research. Despite recent advances and advantages over traditional machine learning methods, deep neural networks have yet to have permeated significantly into neuroscience studies, particularly as a tool for discovery. This dissertation presents well-established and novel tools for unsupervised learning which aid in …

Effects Of Adolescent Alcohol Binge Drinking On Prefrontal Myelin, Wanette M. Vargas-Rodriguez

Doctoral Dissertations

Alcohol binge drinking is highly prevalent in teenagers and is associated with various harmful health effects and social problems. During adolescence, brain regions such as the prefrontal cortex (PFC) are still undergoing active development, characterized by increases in white matter volume. While the morphological details and the cellular and molecular sequences governing adolescent white matter development are not fully known, it is known that this development process is sensitive and can be disrupted. Although consumption of alcohol in a binge drinking pattern has been linked to lower white matter integrity in humans, it is important to determine if alcohol is …

Alterations To Maternal Behavior And Brain By Exogenous Estrogen Exposure, Mary Catanese

Doctoral Dissertations

Maternal care is critical for the development and long-term success of offspring. Poor maternal care can have profound effects on offspring that can last into adult life. Despite our understanding of the role of endogenous estrogen in maternal behavior, the potential effects of exogenous estrogens (xenoestrogens) on maternal behavior and brain remain poorly understood. The active synthetic estrogen in contraceptive pills, 17α-ethinyl estradiol (EE2), is widely used as a positive control for estrogenicity in endocrinology and toxicology studies. Another xenoestrogen, bisphenol A (BPA) alters a broad range of physiological processes including neural development and reproduction. Due to public health concerns …

The Cellular Context Of Estradiol Regulation In The Zebra Finch Auditory Forebrain, Maaya Ikeda

Doctoral Dissertations

Estradiol, traditionally known as a hormone that communicates with distant cells in the body, is also synthesized locally in the brain to act as a neuromodulator. Neuromodulators differ from neurotransmitters in that they simultaneously affect a population of neurons and their actions are not limited to the synapse. One of the many effects of estradiol signaling is rapid modulation of auditory processing in response to external stimuli. The enzyme required for estradiol synthesis, aromatase, is highly expressed in the regions that are involved in higher-order processing of sounds in humans and songbirds. Since zebra finches, a type of songbird, are …

Probiotics As A Treatment For Increased Nighttime Activity In Rhesus Macaques (Macaca Mulatta) Displaying Self-Injurious Behavior, Lauren L. Stanwicks

Masters Theses

Self-injurious behavior (SIB) is a behavioral pathology seen in a small percentage of humans and non-human primates. In one previous study, macaques with SIB had more sleep disruption than controls, but observations were limited. Two studies were conducted: a baseline study to investigate nighttime activity in rhesus macaques (Macaca mulatta) displaying SIB and controls, and a probiotic study to assess probiotic Bifidobacterium infantis 35624 for high nighttime activity. Subjects were 13 rhesus macaques, 5 with SIB (3 females; 1 SIB). Videocapture of Nighttime Activity (VNRA) was developed to record in complete darkness. IR-receptive webcams were connected to a …

A Rat Model Of Cognitive Bias And The Effect Of Acute Corticosterone, Kai Wang

Electronic Thesis and Dissertation Repository

In humans, affective states can influence cognitive processes, resulting in a phenomenon referred to as “cognitive bias”. Rodents exhibit similar biases during the interpretation of ambiguous cues. It has been shown that cognitive bias shifts towards the negative valence (pessimism) when animals are under chronic stress manipulations. However, the effects of acute stress on cognitive bias have not been well established in an animal model. Here, a non-operant appetitive task using fluid rewards and distinct visual/tactile cues was developed to examine cognitive bias in male rats. Corticosterone was used to mimic stress levels similar to acute restraint stress. It was …

Understanding The Differences Between Neuronal Calcium Sensor Proteins: A Comparison Of Neurocalcin Delta And Hippocalcin, Jeffrey M. Viviano

Graduate School of Biomedical Sciences Theses and Dissertations

Many neuronal functions, including learning and memory are driven by changes in intracellular Ca2+concentrations. The Neuronal Calcium Sensor (NCS) family of proteins is responsible for mediating the response to calcium. They are typically comprised of 4 EF hands; of which EF 2, 3, and 4 bind calcium.

Hypothesis: NCS proteins carry out unique, non-overlapping functions, and that specific characteristics of the family can be mapped to precise regions of the proteins.

Results: The effect on the following properties were investigated primarily on two highly similar NCS proteins, Neurocalcin Delta (NCALD) and Hippocalcin (HPCA): (1) Response to calcium was determined through …

Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla

Electronic Thesis and Dissertation Repository

Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR₁ and 5-HT_2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT_2A/CRs. The first purpose of this thesis was …

The Role Of Cholinergic Neurotransmission In Sensory Filtering And Sensorimotor Gating, Erin Azzopardi

Electronic Thesis and Dissertation Repository

At every moment, our brain is bombarded with sensory information. How we filter and process sensory information is critical for daily functioning and cognition. Examples of sensory filtering include habituation (a progressive decrease in responding) and prepulse inhibition (PPI, gating of responding). Our aim is to understand the differential role acetylcholine (ACh) plays in these processes.

To study this we used both reflexive (acoustic startle response: ASR) and non-reflexive (locomotor) behaviours. PPI is hypothesized to occur via inhibitory cholinergic projections from the Pedunculopontine Tegmental Nucleus (PPT) to the startle pathway. The role of ACh in habituation of reflexive and non-reflexive …

Examining Relationships Between Basic Emotion Perception And Musical Training In The Prosodic, Facial, And Lexical Channels Of Communication And In Music, Jamie Twaite

Dissertations, Theses, and Capstone Projects

Research has suggested that intensive musical training may result in transfer effects from musical to non-musical domains. There is considerable research on perceptual and cognitive transfer effects associated with music, but, comparatively, fewer studies examined relationships between musical training and emotion processing. Preliminary findings, though equivocal, suggested that musical training is associated with enhanced perception of emotional prosody, consistent with a growing body of research demonstrating relationships between music and speech. In addition, few studies directly examined the relationship between musical training and the perception of emotions expressed in music, and no studies directly evaluated this relationship in the facial …