Life Sciences Commons^™

Effects Of Mercury On The Dopamine Transporter Cell Surface Expression In Pc12 Cells, Christina Hui

Student Theses

Environmental factors, such as heavy metal exposures, have been suggested to have an impact not only on neurodegenerative disease, such as Parkinson’s disease, but also on psychostimulants abuse and their toxicity. In this study, two questions were addressed: 1) effects of mercuric chloride on parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP⁺) induced cytotoxicity and 2) effects of mercuric chloride on cell surface dopamine transporter. Pheochromocytorma cells (PC12) were treated with various concentrations of mercuric chloride (0.02~2.0 ppm) for 4 hours with and without 0.1 mM MPP⁺. Significant potentiation of toxicity was observed when there was co-treatment with 0.5 ppm …

Visual Entrainment Of Perception-Related Neural Oscillations As A Mechanism For Maintaining Rhythmic Temporal Expectations Across A Wide Range Of Frequencies, Michael James Gray

Dissertations, Theses, and Capstone Projects

Visual sensitivity fluctuates rhythmically, in-synch with ongoing, EEG-recorded neural oscillations across a wide range of frequencies (~1-25hz). Some recent work has suggested that these perception-related neural oscillations can be entrained by rhythmic visual stimulation. Evidence is also emerging that the entrainment of ongoing oscillations in visual and auditory cortices is involved in rhythmic temporal expectations. In the introduction chapter, I attempt to bridge these bodies of literature and hypothesize that rhythmic visual stimuli automatically entrain ongoing, perception-related neural oscillations and that this mechanism supports the maintenance of rhythmic temporal expectations. Chapters 2 and 3 address this hypothesis from different angles. …

Neural Correlates Of Automatic Emotional Processing And Emotion Regulation In Empathy And Psychopathy-Related Coldheartedness, Danielle Difilipo

Dissertations, Theses, and Capstone Projects

Psychopathy is a personality disorder that is defined, in part, by a lack of empathy. Psychopathy-related empathic deficits have been associated with atypical behavioral and neural responses to emotional facial expressions. Although the mirror neuron system (MNS) has been implicated in empathy, very few studies have examined the role of MNS functioning as it pertains to empathy impairments in psychopathy. Moreover, there is very little empirical research regarding emotion regulation in psychopathy, and specifically whether emotional responses can be intentionally upregulated. The present study sought to clarify whether the MNS is functionally intact in adults with subclinical psychopathic traits, particularly …

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of the …

Emotion Processing Deficits In Psychopathy: Does Cueing To Relevant Facial Features Increase Cognitive And Emotional Empathy?, Shawn E. Fagan

Dissertations, Theses, and Capstone Projects

Psychopathy is a multifaceted disorder characterized by a lack of cognitive and emotional empathy. The traditional model of psychopathy divides the disorder into two factors: Factor 1 consists of the interpersonal and affective traits of psychopathy while Factor 2 measures antisocial behaviors and lifestyle choices. The attention-to-the-eyes hypothesis argues that psychopathic individuals have impaired emotion recognition (specifically for fear) due to deficits in orienting attention to salient facial features like the eyes. Psychopathic individuals also display blunted autonomic responding to emotional stimuli, though whether this is due to attention-orienting deficits remains to be clarified. The present project investigated whether empathy-related …

The Role Of The Direct And Indirect Basal Ganglia Pathways In The Learning, Performance, And Goal-Directed Control Of Action Sequences, Eric Garr

Dissertations, Theses, and Capstone Projects

Animals engage in intricately woven action sequences that are constructed from trial-and-error learning, but the mechanisms by which the brain links together individual actions which are later recalled as fluid chains of behavior are not fully understood. The aim of this dissertation is to investigate the learning and goal-directed control of action sequences in rats. Experiment 1 addresses a question that comes out of a reinforcement learning model of action sequencing: how does the extent of training change how the performance of an action sequence is impacted by reward devaluation. The data show that action sequences remain goal-directed overall regardless …

Structure And Function Of Dopamine In The Inner Ear And Auditory Efferent System Of A Vocal Fish, Jonathan T. Perelmuter

Dissertations, Theses, and Capstone Projects

The neuromodulator dopamine is considered essential for coordinating the internal motivational state of an organism with appropriate behavioral responses to stimuli in the external environment. This could be accomplished by modifying the function of neural circuits involved in sensory processing such that they are “tuned in” and optimally sensitive to important stimuli during critical time windows. While dopamine modulation of auditory processing has been studied in the central nervous system, neuromodulation can also occur outside the brain, in the inner ear. The majority of investigations of dopamine in the ear are conducted using rodents and focus on its role in …

Murine Genetic Variance In Sugar And Fat-Conditioned Flavor Preferences: Roles Of Dopamine, Opioid And Nmda Receptors And Nutritive Sensing, Tamar T. Kraft

Dissertations, Theses, and Capstone Projects

As obesity and diabetes have emerged as a severe public health crisis, understanding the mechanisms underlying the consumption of sugars and fats has become a topic of vigorous study. From a biological standpoint, genetic dispositions, neurochemical and hormonal influences, and predetermined orosensory and postingestive signals that modulate the hunger and satiety process may govern physiological aspects of the obesity puzzle. In addition to an innate appetite and attraction for simple carbohydrates and fats, learning plays an important role in modulating preferences for sugar- and fat-rich foods in rodents, including inbred mouse strains. Marked genetic variance has been observed among murine …

The Interaction Of Attention And Memory On The Reorienting Negativity, John C. Moses

Dissertations, Theses, and Capstone Projects

The three-stage model of distraction asserts that when we are presented with salient but task-irrelevant information, our sensory systems first detect the distracting stimulus by way of sensory memory buffers, which is indicated electrophysiologically by the mismatch negativity (MMN). Following detection, attentional resources are involuntarily allocated towards the processing of the distraction, as represented by the P3a. Finally, attentional resources are shifted away from the distracting stimulus and returned to the task-relevant information, as indicated by the reorienting negativity (RON). A great deal of research has focused on this last step in the model, largely centering around defining the mechanisms …

Voluntary Oral Methamphetamine Reveals Susceptibilities To Spatial Memory Deficits, Decreased Dopamine Marker Expression And Increased Neuroinflammation In The Hippocampus Of Male And Female Mice, Jorge A. Avila

Dissertations, Theses, and Capstone Projects

Methamphetamine is an addictive illicit psychostimulant that produces lasting neurochemical and behavioral changes. The mechanisms underlying these deficits have been characterized in animal models using extremely high doses. Currently, better translational models are needed to understand the onset and progression of these deficits that more accurately reflect the gradual and voluntary dosing parameters as chosen by an abuser. To that end, a new model of methamphetamine administration, labeled Voluntary Oral Methamphetamine Administration (VOMA), offers a means to examine the progression of neurotoxicity, behavioral deficits, and the addiction process through a voluntary consumption framework.

Female populations show consistent vulnerabilities to methamphetamine, …

Neurogenesis Is Altered Between And Across Brain Regions After Neurodegeneration And Injury, Alice Perez

Dissertations, Theses, and Capstone Projects

Adult neurogenesis is the addition of new neurons in the adult brain. In mammals, neurogenesis is largely restricted to the hippocampus and olfactory bulb, which underlie learning, memory, and olfaction. In songbirds, new neurons are incorporated into telencephalic regions that subserve the production, perception, and maintenance of song. Studies of the regulation of neurogenesis have exclusively focused on a single brain region and within a single hemisphere. Interestingly, it has yet to be investigated whether there are correlations between numbers of new neurons across regions and hemispheres within the same animal. Here we examined these differences in a rat model …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Interhemispheric Communication And Lateralization In The Mouse Hippocampus, Jake Jordan

Dissertations, Theses, and Capstone Projects

The hippocampus is essential for memory and spatial navigation. Many theories have been proposed to explain how the hippocampus contributes to cognition; however, none has fully explained relevant neurophysiological and behavioral data. Hemispheric lateralization of hippocampal function has been reported in humans and in rodents, and lateralization of hippocampal neural circuitry has been reported in rodents. Most theories of hippocampal function fail to consider the hippocampus as a bilateral structure with hemispheric differences. Further, proposed theories of hippocampal lateralization have their own limitations in explaining empirical data concerning left/right function. Little is known about communication between the hippocampi across hemispheres. …

Contextually Modulated Avoidance Behavior In Rats Post-Pavlovian Extinction, Lauren Branigan

Theses and Dissertations

The following study sought to examine the psychological substrates of renewal (e.g.., context dependent extinction processes) for conditioned avoidance behaviors in rats. Using signaled active avoidance conditioning, rats acquired two-way shuttle responding, to two different auditory stimuli. These behaviors were then extinguished through exposure to the auditory stimuli where shuttling behavior was now without consequence. Subjects were then tested for renewal of avoidance in three distinct renewal sequences (e.g., ABA vs ABB, AAB vs AAA, and ABC vs ABB) in three separate groups of rats. It was found that subjects showed more responding to a stimulus presented outside of its …

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …

The Integration Of Multiple Sources Of Sonic Hedgehog In The Spinal Cord Contribute To The Production Of First-Born Oligodendrocyte Precursor Cells Which Become Critical For Synapse Remodeling In Response To Adult Motor Neuron Injury, Lev Starikov

Dissertations, Theses, and Capstone Projects

Oligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here I show that interrupting Sonic hedgehog (Shh) signaling originating from nascent ventricular zone derivatives (VZD), motor neurons and the lateral floor plate, almost completely blocks ventral but not dorsal oligodendrogenesis without noticeably affecting early tissue patterning and embryonic development. In the absence of ventral OPCs, dorsal OPCs increase proliferation and populate the entire spinal cord with increased density. In these mutant mice, dOPCs take …

Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, Diego F. Buenaventura

Dissertations, Theses, and Capstone Projects

There are two types of photosensitive cells of the retina that contribute to image formation: Cone photoreceptors that mediate color discrimination and rods that provide photosensitivity in low-light conditions. Given the importance of cones in high acuity and color vision, deficiencies in this cell type that result from ailments such as retinitis pigmentosa and macular degeneration can lead to a debilitating loss of vision. Currently, one of the most pressing goals in the field of retinal development is the elucidation of the gene regulatory networks (GRN) involved in inducing an undifferentiated cell into becoming a functional cone photoreceptor.

Recently, an …

A Defense Of Pure Connectionism, Alex B. Kiefer

Dissertations, Theses, and Capstone Projects

Connectionism is an approach to neural-networks-based cognitive modeling that encompasses the recent deep learning movement in artificial intelligence. It came of age in the 1980s, with its roots in cybernetics and earlier attempts to model the brain as a system of simple parallel processors. Connectionist models center on statistical inference within neural networks with empirically learnable parameters, which can be represented as graphical models. More recent approaches focus on learning and inference within hierarchical generative models. Contra influential and ongoing critiques, I argue in this dissertation that the connectionist approach to cognitive science possesses in principle (and, as is becoming …

Post-Synaptic Mechanisms Of Early And Late Prepulse Inhibition In The Goldfish, Daniel Bronson

Dissertations, Theses, and Capstone Projects

Sensorimotor gating, or prepulse inhibition (PPI), attenuates the startle response during sensory processing by limiting sensory input to the startle circuit. In the goldfish startle circuit, a single action potential in the Mauthner-cell (M-cell) triggers the startle response. PPI in the M-cell is mediated by multiple post-synaptic mechanisms, including the activation of a tonic, shunting inhibition as well as a voltage-sensitive conductance, both of which briefly reduce M-cell excitability. However, the specific channels and pathways that modulate PPI are not fully known. This work further characterizes the post-synaptic conductances that mediate PPI by blocking voltage-gated and inward-rectifying potassium channels, antagonizing …

Novel Biobehavioral Methods For Assessing The Anxiety-Related Attention Bias, Samantha Denefrio

Dissertations, Theses, and Capstone Projects

Anxiety disorders will affect an estimated one in three Americans, significantly impacting emotional health and quality of life. High personal and economic costs make research on the etiology, maintenance, and treatment of anxiety a crucial public health goal. Selective and exaggerated attention towards threat, termed attention bias (AB), has been identified as a core behavioral and neurocognitive mechanism in anxiety. A novel treatment, attention bias modification training (ABMT), targets AB and aims to ameliorate anxiety. Rarely acknowledged, however, are the challenges in the conceptualization and measurement of AB. First, associations between anxiety and AB in anxious populations have been increasingly …

Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh

Dissertations and Theses

No abstract provided.

Using Fundamental Properties Of Light To Investigate Photonic Effects In Condensed Matter And Biological Tissues, Laura A. Sordillo

Dissertations and Theses

Light possesses characteristics such as polarization, wavelength and coherence. The interaction of light and matter, whether in a semiconductor or in a biological sample, can reveal important information about the internal properties of a system. My thesis focuses on two areas: photocarriers in gallium arsenide and biomedical optics. Varying the excitation wavelength can be used to study both biological tissue and condensed matter. I altered the excitation wavelengths to be in the longer near-infrared (NIR) optical windows, in the shortwave infrared (SWIR) range, a wavelength region previously thought to be unusable for medical imaging. With this method, I acquired high …