Life Sciences Commons^™

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Electrophysiological Signatures Of Stress Adaptability In The Bnst-Vta Pathway, Yuka Miura

Dissertations, Theses, and Capstone Projects

Chronic stress has detrimental effects on psychological and physiological health. Incapability to adapt to chronic stress can lead to depression, anxiety disorders, and addiction. The brain regions critical for reward processing share diverse physiological and molecular changes linked to depressive-like behaviors as a result of chronic stress. Cumulative evidence shows that counteraction or prevention of these alterations in neurons, occasionally in a projection-specific manner, can enhance stress adaptation or resilience.

Chronic stress induces various changes in the brain, including in the bed nucleus of the stria terminalis (BNST) and the ventral tegmental area (VTA). The neural projections from the BNST …

Automatic Analysis Of The Frequency, Vigor, And Complexity Of Spontaneous Locomotion Bouts Of Mice With Loss And Gain Of Function Of The G Protein-Coupled Receptor Smoothened In Cholinergic Neurons, Aleksandra Feshchenko

Dissertations, Theses, and Capstone Projects

Locomotion, a fundamental behavior, is classically assessed using simple metrics of velocity and total distance moved in an open field. This behavior however offers rich data about the organization and breadth of actions an animal can take while only facing limitations due to the bio-mechanical constraints of the organism. Importantly, these actions are not biased towards a particular task-solution space imposed by many behavioral paradigms. Here, to analyze motor complexity in freely ambulating mice, we developed a method for the automatic and unbiased identification of locomotor bouts which we call Bout Finder (BF). This analysis utilizes Open Feld data to …

You Hurt My Feelings: Autonomic And Behavioral Responses To Social Exclusion And The Moderating Effect Of Psychopathic Traits, Liat Kofler

Dissertations, Theses, and Capstone Projects

Humans have a fundamental need to form and maintain social connections, and thus experiencing social exclusion is extremely distressing as it threatens this basic human need. Individuals who are socially excluded often respond aggressively, not only towards their ostracizers but also towards innocent bystanders, with ostracism being implicated in extreme acts of violence such as school shootings. However, individual differences in behavior exist within the context of social exclusion as not everyone responds aggressively after being ostracized. Identifying risk factors for retaliatory aggressive behavior following experiences of social exclusion may facilitate the development of targeted interventions aimed at mitigating such …

Ultrastructural Correlates Of Axons And Synapses Belonging To Different Circuits In Ferret Primary Visual Cortex, Anjelique Sawh

Dissertations and Theses

The goal of this study was to determine differences in distinctive layers of mammalian primary visual cortex through analysis of their ultrastructural characteristics. Characterizing brain circuitry using 3-dimensional reconstruction of electron microscopy images, and subsequent ultrastructural analysis of axonal populations provides us with a better understanding of the connectivity of the neural circuits. By quantifying ultrastructural differences in axonal processes such as synaptic densities, types of synapses and their post-synaptic densities (PSDs), mitochondrial volumes, synaptic vesicle aggregates, dendritic targets, and bouton volumes, we aimed to understand whether differences in anatomical specializations among different cortical layers could underlie differences in function …

Development And Characterization Of A Novel, Genetically- Encoded Sensor To Image Sonic Hedgehog Signaling In Functional Circuits, Sonia Bernal

Dissertations, Theses, and Capstone Projects

Dynamic neurotransmitter and neuromodulator signaling in functional circuits is the neural substrate of animal behavior and cognition. The study of said circuits requires tools with sufficient spatiotemporal dynamics that can probe complex signaling patterns and decode their functional relevance by coupling the signal to behavioral output, ideally in awake, behaving animals. Much is known about the role of classical neurotransmitters such as dopamine in behavior, but a wide variety of peptides and small molecules also regulate neuronal transmission. One of these is Shh, whose presence has been observed in a variety of brain regions known to modulate movement, perception, and …

Antisocial Behavior And Callous Unemotional Traits In Youth: A Biosocial Approach, Yong Lin Huang

Dissertations, Theses, and Capstone Projects

Early life presence of antisocial behavior (e.g., aggression/delinquency) and psychopathic/callous-unemotional (CU) traits (lacking empathy/remorse, shallow affect) are precursors to juvenile crime and criminal offending in adulthood. Etiological research on antisocial/CU tendencies has implicated both neurobiological (e.g., alterations in brain function and structure) and environmental (social adversity, prenatal stress) underpinnings. It has been proposed that reward and punishment processing deficits may induce problematic traits and behavior, such that antisocial/CU tendencies may be linked to hypersensitivity to rewards and hyposensitivity to punishment. Studies in this area have generated inconsistent findings and focused primarily on adult and clinical samples, leaving youth and community …

Mitochondrial Distribution Of Glycine Receptors In Motor Neuron Cell Lines, Katsiaryna Milashevich

Student Theses and Dissertations

Although non-essential, glycine plays an important role in major metabolic reactions and is most known for its anti-inflammatory effects. An accumulation of contemporary research has shown that glycine is able to stabilize membrane potential using glycine receptors at the cellular level and to protect mitochondrial function directly, whether it is from inflammation, heavy metal poisoning, or ischemia-induced neuroinflammation. In this research, the existence of a hypothetical mitochondrial glycine receptor is examined. Immunofluorescence imaging was used to examine the presence of the glycine receptor subunits alpha 1 and alpha 2 in both non- differentiated and differentiated neuroblastoma cell lines. The preliminary …

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, …

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 …

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 …

The Invisible Brain Injury Crisis, Michael E. Rosenthal

Capstones

According to the Center for Disease Control and Prevention’s 2013 data, over 282,000 hospitalizations and 2.5 million emergency department visits were at least in part attributable to TBI. In the same year, about 56,000 people died.

Emergency departments in 2012 treated about 329,290 kids under 20 for TBI following an injury taking place during physical activity.

This project explores the rise in traumatic brain injuries and examines the difficult path that some of the survivors have to go through during recovery. By telling the story through my own personal experiences, I guide the reader through what the initial trauma and …

The Nucleus Accumbens Core Dopamine D1 And Glutamate Ampa/Nmda Receptors Play A Transient Role In The Performance Of Pavlovian Approach Behavior, Veronica Dobrovitsky

Dissertations, Theses, and Capstone Projects

The role of the nucleus accumbens core (NAc core) continues to be redefined with newly acquired data on neurochemical mechanisms mediating the learning and performance of behavior. Previous empirical data showed that dopamine transmission at the D1 receptor (D1R) plays a transient role in the expression of learned Pavlovian approach behavior. Here we show that, prior to overtraining, dopamine activity at D1Rs specifically within the NAc core is critical for the performance of approach behavior elicited by the recently-acquired reward-paired cue. Blockade of D1Rs in the NAc core, but not the dorsomedial striatum or NAc shell, disrupted approach responses during …

Modulation Of Spasticity By Trans-Spinal Direct Current Stimulation In Animals With Spinal Cord Injury, Wagdy Mekhael

Dissertations, Theses, and Capstone Projects

Central nervous system injuries usually produce motor impairments that are exacerbated by pathologically altered muscle tone. Abnormal muscle tone interferes with voluntary movement and is associated with loss of dexterity. Prior work in our laboratory demonstrated that 30-second trans-spinal direct current (DC) stimulation can temporarily modify muscle tone in anesthetized spastic mice after spinal cord injury (SCI). These experiments described DC-induced muscle tone responses to be polarity-dependent. That is, anodal stimulation (current passed from the lumbar spine to sciatic nerve) decreased muscle tone, and cathodal stimulation (current passed from the sciatic nerve to the lumbar spine) increased it. The present …

Psychopathy, Empathic Concern, And Emotional-Sentence Processing: An N400 Erp Study, Farren Larson

Student Theses

Using an undergraduate sample, the present study examined how psychopathic traits (assessed by the Psychopathic Personality Inventory-Revised) and empathic concern (assessed by the Interpersonal Reactivity Index) affect emotional-information processing using event-related potentials (ERPs) and a sentential priming paradigm. Participants had their electroencephalogram (EEG) recorded while they silently read sentences with three types of endings: congruent, incongruent, and emotionally negative. We hypothesized that participants with high levels of psychopathic traits and participants with low levels of empathic concern would find the emotionally negative sentence endings less unexpected and disturbing (yielding a smaller N400), compared to participants with low levels of psychopathic …

Dopamine D1 And D3 Receptor Polypharmacology In Cocaine Reward And Cocaine Seeking, Ewa J. Galaj

Dissertations, Theses, and Capstone Projects

Background: In the search for efficacious pharmacotherapies to treat cocaine addiction much attention has been given to agents targeting D1 or D3 receptors because of the involvement of these receptors in cocaine-related behaviors. D1 and D3 receptor partial agonists and antagonists have been shown to reduce cocaine reward, reinstatement of cocaine seeking and conditioned place preference (CPP) in rodents and non-human primates. However, translation of these encouraging results with selective D1 or D3 receptor agents has been limited due to a number of factors including toxicity, poor pharmacokinetic properties and extrapyramidal and sedative side effects.

Purpose: Given the …

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.

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 …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.