Neuroscience and Neurobiology Commons^™

Neuroprotective Strategies Following Experimental Traumatic Brain Injury: Lipid Peroxidation-Derived Aldehyde Scavenging And Inhibition Of Mitochondrial Permeability Transition, Jacqueline Renee Kulbe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) represents a significant health crisis. To date there are no FDA-approved pharmacotherapies available to prevent the neurologic deficits caused by TBI. Following TBI, dysfunctional mitochondria generate reactive oxygen and nitrogen species, initiating lipid peroxidation (LP) and the formation of LP-derived neurotoxic aldehydes, which bind mitochondrial proteins, exacerbating dysfunction and opening of the mitochondrial permeability pore (mPTP), resulting in extrusion of mitochondrial sequestered calcium into the cytosol, and initiating a downstream cascade of calpain activation, spectrin degradation, neurodegeneration and neurologic impairment.

As central mediators of the TBI secondary injury cascade, mitochondria and LP-derived neurotoxic aldehydes make promising …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

The Role Of Endoplasmic Reticulum Stress In Ethanol-Induced Neurodegeneration, Yongchao Wang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heavy ethanol use causes neurodegeneration manifested by neuronal loss and dysfunction. It is becoming imperative to delineate the underlying mechanism to promote the treatment of ethanol-induced neurodegeneration. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases. This study aims to investigate the role of ER stress in ethanol-induced neurodegeneration. In experimental design, adult mice were exposed to binge ethanol drinking by daily gavage for 1, 5, or 10 days and the response of ER stress was examined. We found the induction of ER stress appeared at 5 days and remained at 10 days. Moreover, …

Exploring The Role Of Insulin Receptor Signaling In Hippocampal Learning And Memory, Neuronal Calcium Dysregulation, And Glucose Metabolism, Hilaree N. Frazier

Theses and Dissertations--Pharmacology and Nutritional Sciences

In the late 90’s, emerging evidence revealed that the brain is insulin-sensitive, highlighted by broad expression of brain-specific insulin receptors and reports of circulating brain insulin. Contemporary literature robustly supports the role of insulin signaling in normal brain function and suggests that insulin-related processes diminish with aging, evidenced by decreased signaling markers, reduced insulin receptor density, and lower levels of insulin transport across the blood-brain barrier. In the context of pathological cognitive decline, clinical trials using intranasal insulin delivery have reported positive outcomes on memory and learning in patients with mild cognitive decline or early-stage Alzheimer’s disease. However, while the …

Aptamer Functionalized Zinc Oxide Field Effect Transistors For Odor Detection, Michael D. Aldridge

Graduate Theses, Dissertations, and Problem Reports (ETD)

Odor detection and identification are complex processes, and tasks that currently only animals do well. There is a pressing need for an electronic nose, or eNose, with good sensitivity, selectivity, and speed that mimics that ability. Food quality control operations, environmental sensing, occupational safety, and the defense sectors all require systems that can rapidly and reliably detect trace levels of volatile organic compounds. The goal of this work is to create a biologically inspired device which can accurately detect and identify odors at concentrations consistent with the most sensitive biological systems.

In order to mimic a natural olfactory system, we …

Identifying Dopamine Receptor Genes And Transcription Marbled Crayfish, Wolfgang Stein, Saisupritha Talasu

Faculty Publications – Biological Sciences

Modulatory transmitters are major contributors to nervous system plasticity and behavioral flexibility, they determine motivational states and are involved in psychiatric and neurological disorders. Neuromodulators act through a variety of distinct receptors and due to the diversity in receptor subtypes and distribution, a single neuromodulator can exert many different actions. A prerequisite to understand the ways modulators work is thus to identify which receptors are expressed in an animal.

I studied which Dopamine receptors are present in the Procambarus virginalis, a highly invasive species of all female genetic clones with high quality genome and transcriptomes. Their broad behavioral repertoire makes …

The Bionic Brain: Pragmatic Neuroethics And The Moral Plausibility Of Cognitive Enhancement, Peter A. Depergola Ii

Philosophy, Theology and Religious Studies Faculty Publications

The seemingly infinite possibilities of contemporary neuroscience span from the augmentation of memory, executive function, appetite, libido, sleep, and mood, to the maturation and development of emotional health and personality. These prospects hint at the capacity to alter neurocognitive conceptions of reality. They also mark the unavoidable inculcation of nuanced individual responses, perhaps radical, to these “tailor- made” perceptions. Hence, there exists certain neuroethical, and even more generally, existential risks within this fascinating and expeditious enterprise. The primary question in the context of present-day neurotechnology is not what can be done, but what should be. To that end, this paper …

Neural Processing Of Communication Signals: The Extent Of Sender–Receiver Matching Varies Across Species Of Apteronotus, Kathryne M. Allen, Gary Marsat

Faculty & Staff Scholarship

As communication signal properties change, through genetic drift or selective pressure, the sensory systems that receive these signals must also adapt to maintain sensitivity and adaptability in an array of contexts. Shedding light on this process helps us to understand how sensory codes are tailored to specific tasks. In a species of weakly electric fish, Apteronotus albifrons, we examined the unique neurophysiological properties that support the encoding of electrosensory communication signals that the animal encounters in social exchanges. We compare our findings to the known coding properties of the closely related species Apteronotus leptorhynchus to establish how these animals …

Molecular And Biochemical Phenotypes Underlying Reactive Astrocytosis In Primary Optic Nerve Head Astrocytes, Anita Kirti Ghosh

Master's Theses

Glaucoma is a progressive optic neuropathy that manifests in a pathological triad of optic nerve head remodeling, damage to optic nerve axons, and retinal ganglion cell death. Optic nerve head astrocytes (ONHAs) are the primary cell type in the optic nerve head. ONHAs undergo reactive astrocytosis, an activated phenotype characterized by altered gene and protein expression and increased cell migration and proliferation, early in the disease pathology. Reactive astrocytosis is thought to underlie optic nerve head remodeling. The first goal of this thesis was to determine if exposure of primary adult rat ONHAs to hyperbaric pressure (25-30 mm Hg above …

The Effect Of Mild Cognitive Impairment On Anxiety In Older Adults In American And Ukraine, Eleanor Ryan

Senior Honors Theses and Projects

With the growing population of elderly individuals throughout the world, the study of their emotional distress is ever poignant to society. This is especially true when these individuals have cognitive impairment. The research, in regards to Eastern European individuals, is lacking. To gain a better understanding of this understudied population, elderly people with Mild Cognitive impairment (MCI) from both Ukraine and the United States were studied. It was found that the anxiety rates of the Ukrainian MCI group were significantly higher than both the United States MCI group and the Ukraine control (p = 0.004). Purpose The purpose of this …

Targeting Maladaptive Plasticity After Spinal Cord Injury To Prevent The Development Of Autonomic Dysreflexia, Khalid C. Eldahan

Theses and Dissertations--Physiology

Vital autonomic and cardiovascular functions are susceptible to dysfunction after spinal cord injury (SCI), with cardiovascular dysregulation contributing to morbidity and mortality in the SCI population. Autonomic dysreflexia (AD) is a condition that develops after injury to the sixth thoracic spinal segment or higher and is characterized by potentially dangerous and volatile surges in arterial pressure often accompanied with irregular heart rate, headache, sweating, flushing of the skin, and nasal congestion. These symptoms occur in response to abnormal outflow of sympathetic activity from the decentralized spinal cord typically triggered by noxious, yet unperceived nociceptive stimulation beneath the level of lesion. …

Neural Circuits Underlying Rodent Sociality: A Comparative Approach, Nicole S. Lee, Annaliese K. Beery

Neuroscience: Faculty Publications

All mammals begin life in social groups, but for some species, social relationships persist and develop throughout the course of an individual’s life. Research in multiple rodent species provides evidence of relatively conserved circuitry underlying social behaviors and processes such as social recognition and memory, social reward, and social approach/avoidance. Species exhibiting different complex social behaviors and social systems (such as social monogamy or familiarity preferences) can be characterized in part by when and how they display specific social behaviors. Prairie and meadow voles are closely related species that exhibit similarly selective peer preferences but different mating systems, aiding direct …

Cross-Limb Dynamics Of Postural Tremor Due To Limb Loading To Fatigue: Neural Overflow But Not Coupling, Steven Morrison, Justin Kavanagh, Karl Newell

Rehabilitation Sciences Faculty Publications

Many experiments have shown independence of the index finger dynamics under bilateral postural tremor protocols. Here we investigated in young adults the dynamics of bilateral multidirectional postural tremor and forearm muscle activity under the progressively fatiguing conditions supporting an external weight to the point of induced postural failure. When no loads were applied, tremor in the vertical (VT) and mediolateral (ML) directions was similar with prominent peaks within 2- to 4-Hz and 8- to 12-Hz bandwidths. Contrastingly tremor in the anterior-posterior (AP) direction was characterized by a single peak between 0 and 2 Hz. Although no tremor coupling occurred cross …

Domestication And Cognitive Complexity, David R. Brodbeck, Madeleine I. R. Brodbeck, Keeghan Rosso

Animal Sentience

Marino and Merskin (2019) list a number of tasks that sheep can perform well. As comparative psychologists, we are not surprised by these results. Indeed, many domesticated animal species show similar abilities.

The Perfecting Of The Octopus, Ila France Porcher

Animal Sentience

Cephalopods split away from the phylogenetic tree about half a billion years ago, and octopus evolution has been accelerated by an extremely low survival rate. This helps explain why this unusual animal presents qualities found in no other. It has a radially organized nervous system with a processing centre for each of its eight tentacles. Yet, although this might suggest that each tentacle has its own centre of consciousness, it remains just one animal, with one mouth to feed, and one life to lose, and it behaves as if it is centrally controlled. Its capacity for a range of intelligent …

Effects Of The Dual Orexin Receptor Antagonist Dora-22 On Sleep In 5xfad Mice, Marilyn J. Duncan, Hannah Farlow, Chairtra Tirumalaraju, Do-Hyun Yun, Chanung Wang, James A. Howard, Madison N. Sanden, Bruce F. O'Hara, Kristen J. Mcquerry, Adam D. Bachstetter

Neuroscience Faculty Publications

Introduction: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD.

Methods: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. Aβ plaques, Aβ levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively.

Results: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing Aβ levels, …

Investigating Neurogenesis As A Veritable Epigenetic Endophenotype For Alzheimer's Disease, Layne Wells

Scripps Senior Theses

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by progressive amyloid plaque aggregation, neurofibrillary tangles, and cortical tissue death. As the prevalence of AD is projected to climb in coming years, there is a vested interest in identifying endophenotypes by which to improve diagnostics and direct clinical interventions. The risk for complex disorders, such as AD, is influenced by multiple genetic, environmental, and lifestyle factors. Significant strides have been made in identifying genetic variants linked to AD through the genome-wide association study (GWAS). It has been estimated in more recent years, however, that GWAS-identified variants account for limited …

Trpm7 Channels As A Bioassay Of Internal And External Mg2+, Charles T. Luu

Browse all Theses and Dissertations

Magnesium is an important divalent metal cation that is involved in numerous cellular functions. The details of cellular Mg2+ regulation, homeostasis and transport remain unclear. Magnesium transporter protein (MagT1) is a Mg2+ transporter and deficiency of this protein has been reported to lead to impaired Mg2+ influx and a decreased cytoplasmic [Mg2+]. Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed membrane protein containing a channel pore and a C-terminal alpha-type serine/threonine protein kinase domain. Importantly, TRPM7 channel is believed to conduct both Mg2+ and Ca2+. In the present study, we investigated if TRPM7 can be used as a …

Expression Of Tumor Necrosis Factor-Alpha In A Chick Model Of Stress Vulnerable, Treatment – Resistant Depression, Mary Katherine Jourdan

Electronic Theses and Dissertations

An increasing body of literature suggests a Major Depressive Disorder subpopulation, Treatment Resistant Depression (TRD), is associated with an increased immune response. More than a decade of research has identified and begun to validate a novel animal model of TRD. This study sought to determine whether TNF-α levels would be altered due to isolation stress and differentiated between stress-vulnerable and -resilient strains. Black Australorp and Production Red chicks were placed into isolation for varying times during which Distress Vocalization (dVoc) rates were calculated and transformed into entry into behavioral despair percent thresholds. Blood levels of TNF- α were quantified via …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

No Evidence That Portion Size Influences Food Consumption In Male Sprague Dawley Rats, Fabien Naniex, Sophie C. Pinder, Megan Y. Summers, Renee M. Rouleau, Eric Robinson, Kevin P. Myers, James E. Mccutcheon

Faculty Journal Articles

In studies of eating behavior that have been conducted in humans, the tendency to consume more when given larger portions of food, known as the portion size effect (PSE), is one of the most robust and widely replicated findings. Despite this, the mechanisms that underpin it are still unknown. In particular, it is unclear whether the PSE arises from higher-order social and cognitive processes that are unique to humans or, instead, reflects more fundamental processes that drive feeding, such as conditioned food-seeking. Importantly, studies in rodents and other animals have yet to show convincing evidence of a PSE. In this …

Relations Among Maternal And Paternal Behavior And Children's Stress Biology, S.K. Jiaming Lin, Stacey N. Doan, John Milton

Scripps Senior Theses

Parenting behavior has been shown to have a wide range of effects, influencing children’s psychological and biological stress outcomes. Most research focuses on maternal parenting behaviors, with few studies observing the effects of paternal behaviors or the influence of both parents on their children. In this study, the relationship between maternal and paternal parenting behaviors was examined in its association to predict children’s cortisol levels. Cultural differences in parenting styles was also observed. American (N=86) and Chinese (N=97) families participated in the study, with parents reporting their behaviors. Children’s cortisol was collected during a stressor task and correlational analysis was …

Evidence-Based Probiotic Intervention For Behavioral And Social Deficits In Autism Spectrum Disorder, Allisen To

Scripps Senior Theses

Autism Spectrum Disorder (ASD) refers to a heterogeneous neurological condition characterized by repetitive and restrictive behaviors and social communication deficits. ASD diagnoses are at a record high, at approximately 1 in 59 children according to the US Center for Disease Control. Currently, there are no available interventions that effectively treat the core symptoms of ASD. All pharmaceutical options address comorbid side effects of ASD but not core deficits and are particularly associated with negative side effects. Additionally, there are economic and geographic barriers that can prevent families of individuals with ASD from seeking or receiving effective interventions. Many of the …

Shining Light On An Amygdala -- Brainstem Connection Important For Attention Processing, Jose Carlos Cano

Open Access Theses & Dissertations

We are continuously being exposed to an exorbitant amount of sensory information, which should result overwhelming. However, the nervous system operates several intrinsic sensory filtering mechanisms that allow us to cope with such sensory cluttering and shape appropriate behavior. Sensorimotor gating is a pre-attentive neuronal filtering mechanism that gates superfluous sensory information, and orients attentional resources towards salient information processing. Its relevance becomes in individuals suffering from schizophrenia and several otherwise unrelated neuropsychiatric disorders where sensorimotor gating is impaired. To understand the neural impaired mechanisms, extensive research studies have focused on first identifying the neural substrates underlying sensorimotor gating. This …

Identification Of The Cell Type Expressing The Glycine Transporter 1 (Glyt1) In The Thalamus, Patricia A. Lozano

Open Access Theses & Dissertations

Glycine acts as an inhibitory neurotransmitter and a co-agonist of NMDAR at the glutamatergic synapses. Termination of glycinergic neurotransmission is achieved by glycine transporter 1 (GlyT1) and glycine transporter (GlyT2). Both transporters are expressed in the spinal cord, brainstem and cerebellum, but GlyT1 is also expressed in the retina and the forebrain. Previous studies have described the role and cyto- architecture of GlyT1 in the caudal areas of the brain and retina, but not in the structures of the forebrain. Based on our preliminary data, GlyT1 is highly expressed in the thalamus, an area involved in sensory and motor signal …

U.S. Perceptions Of Economic Mobility Since The Enactment Of Nafta And Their Impact On American Politics And Society, Jairemy Quinton Edwards

Open Access Theses & Dissertations

In this study, I examine how perceptions of NAFTA developed over 20 years since its enactment, measured as perceived economic mobility in 2016, have affected more recent public perceptions leading to increased, controversial tendencies towards nationalism, protectionism, and pessimism about the future of the U.S. economy. I then assess whether and how such perceptions in turn may have affected voter perceptions about Donald Trump, setting the stage for his 2016 election victory. Therein, I have found that among U.S. voters in 2016, those with perceptions of reduced economic mobility since the enactment of NAFTA were significantly more likely to have …

The Language Content Of Computer-Mediated Versus Face-To-Face Motivational-Type Interviews, Karla Deyanira Llanes

Open Access Theses & Dissertations

Motivational Interviewing (MI) is an extensively used technique to facilitate behavior change by increasing a person's own motivation and commitment toward change. Recently, several innovative and effective ways to conduct motivational interviews have emerged. However, one potential option has not been investigated: the utility of conducting a motivational interview via computer. The current study begins to address this gap in knowledge by comparing the language content of computer-mediated motivational-type interviews and face-to-face motivational-type interviews. The motivational-type interviews were conducted with young adults who reported ambivalence about their level of recreational marijuana use. Specifically, non-marijuana users, occasional marijuana users, and frequent …

The Effectiveness Of The Natural Ear On Adults Ability To Accurately Match Pitch, Kendra Nicole Rosales

Open Access Theses & Dissertations

Background: Many theories, such as oral motor, perceptual, and sensorimotor deficits, have been posited to explain inaccurate pitch matching abilities. The current study identifies with the sensorimotor deficit theory and found it to be the most plausible explanation for inaccurate singing abilities. The Natural Ear (NE) program was designed to process voice productions in real-time and filter out the discordant harmonics, allowing a person to hear only their F0.

Purpose: The purpose of this study was to examine the effectiveness of the Natural Ear program in increasing pitch matching accuracy in singers.

Methods: A total of 50 participants were included …

Thermal Block Of Action Potentials Is Primarily Due To Voltage-Dependent Potassium Currents: A Modeling Study, Michael W. Jenkins, Hillel J. Chiel

Faculty Scholarship

Objective. Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. Approach. To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. Main results. Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature …

Soft-Surface Grasping: Radular Opening In Aplysia Californica, Catherine E. Kehl, Joey Wu, Sisi Lu, Richard F. Drushel, Rebekah K. Smoldt, Hillel J. Chiel

Faculty Scholarship

Grasping soft, irregular material is challenging both for animals and robots. The feeding systems of many animals have adapted to this challenge. In particular, the feeding system of the marine mollusk Aplysia californica, a generalist herbivore, allows it to grasp and ingest seaweeds of varying shape, texture and toughness. On the surface of the grasper of A. californica is a structure known as the radula, a thin flexible cartilaginous sheet with fine teeth. Previous in vitro studies suggested that intrinsic muscles, I7, are responsible for opening the radula. Lesioning I7 in vivo does not prevent animals from grasping and ingesting …