Oxycodone Withdrawal Is Associated With Increased Cocaine Self-Administration And Aberrant Accumbens Glutamate Plasticity In Rats, Shailesh N. Khatri, Hanaa Ulangkaya, Erin E. Maher, Safiyah M. Sadek, Mei Hong, Andrea M. Woodcox, William W. Stoops, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid with- drawal is associated with increased likelihood of cocaine use, which may represent an attempt to ameliorate opioid withdrawal effects. Clinically, 30% of co-using individuals take opioids and cocaine exclusively in a sequential manner. Preclinical studies evaluating mechanisms of drug use typically study drugs in isolation. However, polysubstance use is a highly prevalent clinical issue and thus, we established a novel preclinical model of sequential oxycodone and cocaine self-administration (SA) whereby rats acquired oxycodone and cocaine SA in an A-B-A-B design. Somatic signs of withdrawal were evaluated …

Modulation Of Persistent Inward Currents With Changes In Posture And Cutaneous Sensory Input, Ryan William Weller

Theses and Dissertations (Comprehensive)

Spinal motor neuron (MN) persistent inward currents (PIC) increase and sustain the MN output. PIC is amplified by descending monoamines and reduced by afferent inhibition. There is strong coupling between plantar cutaneous sensory input and lower limb MNs. Given that monoaminergic drive is altered with postures and motor tasks, our purpose was to assess posture-dependent plantar cutaneous sensory modulation of tibialis anterior (TA) MNs. We hypothesize that: 1) a supine position will suppress PIC, 2) removing the load from the bottom of the heel will inflate PIC, and 3) cutaneous stimulation of the plantar aspect of the heel will reduce …

Effects Of The Cb1 Receptor Antagonist, Am251, On Maternal Behavior In Long-Evans Rat Dams, Jennifer Aguilera-Fonseca, Karla Colley, Eddie Galarza, Atoria Hamm, Joe Morse, Rachel Ntor, Destiny Pichardo, Vincent P. Markowski

McNair Scholars Program

No abstract provided.

Investigating The Roles Of Dapk, P53/Cep-1, And Mitochondrial Damage In Necrotic Neurodegeneration In C. Elegans, Anil Singh

Dissertations and Theses

Stroke is one of the leading causes of death in the U.S., with minority groups, suffering higher fatality rates. Stroke is caused by ischemia, where occlusion of blood supply to the brain results in neurodegeneration. Most of the damage is attributed to excitotoxicity, where an accumulation of the neurotransmitter glutamate in the synapse overstimulates postsynaptic neurons and ultimately leads to cell death (largely by necrosis). Stroke treatments are often ineffective, due to the delay between the onset of stroke and the delivery of effective treatment. To address this, we focus our study on putative later-acting mediators of excitotoxicity such as …

Gaba Transporter Loss-Of-Function Mutations In Pediatric Epilepsy: Neural Mechanisms And A Novel Fatty Acid Based Therapeutic Approach, Alessandra G. Jester

Graduate Student Theses, Dissertations, & Professional Papers

An increasing number of spontaneous mutations in the GABA transporter gene SLC6A1 (GAT-1) have been associated with pediatric epilepsy and neurodevelopmental disorders. The molecular mechanisms and impact of mutations on GABA homeostasis and neuronal circuit function are poorly understood. Furthermore, there are currently no validated therapeutic approaches to treat patients. A de novo mutation (S295L) in the GABA transporter gene SLC6A1 that was identified in a pediatric patient was introduced into a human cDNA construct, and mutant and wild-type transporters were expressed and studied in Xenopus oocytes by voltage clamp and radiolabeled GABA flux measurement. In addition, the effect of …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

UROP Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

UROP Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …

Characterizing Resting Cerebral Blood Flow In Obsessive-Compulsive Disorder With Arterial Spin Labeling, Hannah R. Wild

Theses and Dissertations--Psychology

Obsessive-compulsive disorder (OCD) is a condition characterized by intrusive thoughts (obsessions) and ritualistic behaviors (compulsions) profoundly impacting daily functioning and quality of life. Neuroimaging studies using various techniques have revealed inconsistent resting cerebral blood flow (rCBF) patterns in OCD patients, particularly within the cortico-striatal-thalamo-cortical (CSTC) circuit and sensorimotor network. Arterial Spin Labeling (ASL) MRI offers a promising, noninvasive method for directly measuring rCBF. This study, using data from the Yale HCP Trio study, analyzed unmedicated OCD patients and healthy controls, who underwent two consecutive resting pulsed-ASL scans. OCD patients with lower obsessional severity exhibited higher perfusion in the pre- and …

Extracellular Free Water As An Imaging Biomarker Of Neuroinflammation, Cristina N. Pinheiro

Theses and Dissertations--Psychology

Older adults experience a chronic state of heightened immune response referred to as “inflammaging” which can be observed by detecting levels of proinflammatory cytokines in blood serum. These proinflammatory cytokines are secreted in the central nervous system and may also enter the brain through the blood brain barrier. Previous literature has suggested that extracellular free water, a magnetic resonance imaging metric, may allow us to detect alterations in the extracellular space which are thought to correlate with inflammation in the central nervous system. This study examined the correlation between two proinflammatory cytokines, IL-6 and TNFα, collected longitudinally and cross-sectionally imaged …

Understanding The Significance Of Object Recognition In Cowbirds: Exploring The Interplay Of Cognition, Social Behaviour And Reproductive Success, Eric Rushton

Theses and Dissertations (Comprehensive)

Every day, animals use cognitive processes to make decisions in their environment such as those regarding food sources, threats and mates. One such important process provides the ability to recognize objects and individuals in order to guide future actions. Since object recognition and individual recognition are related processes, they may be linked to social cognition and to fitness; links not commonly explored in the literature. In this thesis I seek to examine (1) how brown-headed cowbirds (Molothrus ater) attend to and react to novel objects in their environment and (2) how this ability to recognize objects is related …

Evaluating Reactive Gliosis In The Brain Of Adult Zebrafish Following The Ingestion Of Nanopolystyrene., Hannah A. Kelehear

College of Graduate Studies: Theses & Dissertations

Polystyrene nanoplastics are one of the most pervasive environmental contaminants and have been shown to infiltrate multiple organ systems following ingestion. Studies in several animal models and humans have demonstrated that nanoplastics can cross the blood-brain barrier. Additionally, there is evidence that plastics will induce an inflammatory response in the brain involving reactive gliosis of microglia and astrocytes. This process has yet to be thoroughly investigated in the zebrafish model system in the context of micro-/nanoplastic ingestion. In the current study, we examined microglial and astrocytic phenotypes in the adult zebrafish telencephalon after consuming food contaminated with 44 nm polystyrene …

The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson

Honors College Theses

The purpose of this research is to improve understanding of the neurodevelopmental effects of embryonic exposure to elevated inflammation and oxidative stress induced by the antipyretic drug acetaminophen (APAP). Our study was the first to examine the interactive effects of APAP and inflammation in zebrafish embryos and how the treatments affect brain development and larval behavior. Experimental groups of zebrafish larvae were exposed to lipopolysaccharide (LPS) to induce inflammation, APAP, or LPS + APAP and larval behavior was analyzed using Ethovision automated behavioral tracking software. We also measured changes in whole-brain Glycogen Synthase Kinase 3 Beta (GSK3B) and GSK3B phosphorylation, …

Target Selection And Enhancement During Attentional Tracking, Marvin R. Maechler

Dartmouth College Ph.D Dissertations

At any waking moment, we are bombarded with more sensory information than we can fully process. Attention is necessary to deal with the dynamic world we live in. One fundamental function of vision and attention is to keep track of moving objects, but what are the targets of attention during tracking?

One of the first theories of attentional tracking predicted that targets would be selected at early processing stages. By employing the double-drift illusion, which dissociates physical and perceived positions of moving objects, we investigated which of these positions is selected for tracking. Contrary to earlier theories and in line …

Androgen Regulation Of The Hpa Axis And Stress-Related Behaviors In Mice: The Role Of Crf And Crf Receptor 1, Krystyna Ann Rybka

Electronic Theses & Dissertations (2024 - present)

Mood disorders such as anxiety and depression are nearly twice as prevalent in women when compared to men, with potential contributing factors involving sex-dependent exposure to gonadal hormones and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Androgen actions through androgen receptors (AR) or actions at estrogen receptors such as ERα, following the conversion of androgens to estradiol, have been shown to regulate stress-related behaviors as well as HPA axis responsiveness. Where androgen actions at AR appear to decrease the stress response and subsequent stress-related behaviors, actions at ERα seem to do the opposite and increase HPA axis reactivity. When the HPA …

Aberrant Lipid Accumulation And Retinal Pigment Epithelium Dysfunction In Prcd-Deficient Mice, Sree Indrani Motipally

Graduate Theses, Dissertations, and Problem Reports (ETD)

Progressive Rod-Cone Degeneration (PRCD) is a peripheral membrane protein predominantly expressed in photoreceptor outer segment (OS) disc membranes with an unknown function. Several mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans. The most common “cysteine to tyrosine” (C2Y) mutation in Prcd leads to progressive retinal atrophy in multiple dog breeds and RP in humans. Canine models harboring the C2Y mutation in Prcd show disorganized OS structure with greatly attenuated photoreceptor OS renewal rates. Recent studies show defects in the photoreceptor nascent disc flattening in the absence of Prcd. However, it is unclear how OS discs eventually …

Evaluating The Potential Of Using Eeg To Monitor Cognitive Workload In Simulated Suborbital Flight, Erik Seedhouse

Journal of Aviation/Aerospace Education & Research

Mental workload can be assessed using electrophysiological measures of brain activity, such as electroencephalography (EEG). EEG signals reveal cortical electrical activity. This cortical activity was recorded using specialized headsets. The focus of this research was to study cognitive performance (CP) in four pilots during simulated suborbital flights under nominal day and night profiles and under contingency day and night profiles. A 14-channel EMOTIV EEG headset measured the participants' brain activity while they flew simulated flights in a Suborbital Spaceflight Simulator (SSFS). Several sessions of EEG data were recorded from each subject, and feature extraction was applied. Data revealed that real-time …

The Effects Of Early Exposure To Prescription/Illicit Drugs And Drug Metabolites On Larval Zebrafish Behavioral And Motor Function Development, Jacob Thomas, Dena Weinberger, Bikram Subedi, Brandon Capps

Murray State Theses and Dissertations

THE EFFECTS OF EARLY EXPOSURE TO PRESCRIPTION/ILLICIT DRUGS AND DRUG METABOLITES ON LARVAL ZEBRAFISH BEHAVIORAL AND MOTOR FUNCTION DEVELOPMENT

A Thesis Presented to the Faculty of the Department of Biology

Murray State University

Murray, Kentucky

In Partial Fulfillment of the Requirements for the Degree of Masters In Science

By Jacob Thomas, B.S., Murray State University

December 2024

Acknowledgements

Brandon Capps, who pretty much did a whole third of the legwork on this project and saved me lots of headaches;

Chandler Maddox, one of the University of Kentucky’s finest undergrads who came in from the top rope with a folding chair …

The Effects Of Diet-Induced Obesity On Cerebral Microvascular Bioenergetics, Alec Anthony Hanshew

Graduate Theses, Dissertations, and Problem Reports (ETD)

Obesity is a worldwide epidemic but is especially a concern in the United States with over 40% of the population being obese. Obesity is known to cause increased metabolic demand, systemic inflammation, peripheral vascular dysfunction, and increased levels of oxidative stress and reactive oxygen species (ROS). However, the role of obesity on cerebrovascular bioenergetic function has not been fully elucidated. This study aimed to determine the impact of diet-induced obesity on cerebrovascular bioenergetics. 72, 6-month-old C57Bl/6 male and female mice were randomized into control and HFD groups. Control mice were subjected to the feeding of standard chow (18% fat, 24% …

Synaptic Zinc Transporters Support Normal Synapse Structure And Function In Mouse Auditory Cortex, Abbey Manning

Graduate Theses, Dissertations, and Problem Reports (ETD)

Many regions of the brain are highly enriched with free zinc inside glutamatergic vesicles at presynaptic terminals. At these synapses, zinc transporter 3 (ZnT3) moves zinc into vesicles where it is co-released with glutamate. Alterations in ZnT3 are implicated in multiple neurodevelopmental disorders, and ZnT3 knock-out (KO) mice – which lack synaptic zinc – show behavioral deficits associated with autism spectrum disorder and schizophrenia. Shank3 is a synaptic scaffolding protein that assists in tethering and organizing structural proteins and glutamatergic receptors in the postsynaptic density of excitatory synapses. The localization of Shank3 at excitatory synapses and the formation of stable …

An Inhibitory Recurrent Network In The Olfactory System, Farzaan Salman

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neuromodulatory circuits are a necessary component of neural flexibility as they are able to act differentially depending on the receptors expressed by their downstream targets. Identifying the synaptic partners of modulatory neurons and determining the neurotransmitter and receptor content of these partners is necessary to identify the rules governing neuromodulatory circuits. In this study, I characterized the circuit of the contralaterally projecting, serotonin-immunoreactive deutocerebral neurons (CSDns), the sole synaptic source of the neuromodulator serotonin in the olfactory circuit of Drosophila melanogaster, by identifying the strongest synaptic partners of the CSDns, and the expression of genes encoding neurotransmitters and receptors of …