Neuroscience and Neurobiology Commons^™

Perinatal Buprenorphine Effects On Offspring Growth, Opioid Withdrawal, And Brain Morphology In Rats, Parker Barnes

Electronic Theses and Dissertations

Opioid use disorder (OUD) impacts 5.6 million people in the US. Buprenorphine (BUP) is a commonly prescribed opioid medication used to treat OUD, including in pregnant women. However, opioid use during pregnancy is associated with poorer infant outcomes including reduced fetal growth, neurodevelopmental deficits, and neonatal opioid withdrawal syndrome (NOWS). Recent clinical data suggests that providing mothers with a lower dose of BUP may result in fewer negative outcomes in infants. Here, a preclinical rodent model of low-dose perinatal BUP exposure was used to study offspring health outcomes in the neonate, juvenile, and adolescent offspring. Dams were given clinically relevant …

Using A Toxic Aging Coin To Assess Hexavalent Chromium-Induced Neurotoxicity., Samuel Thomas Vielee

Electronic Theses and Dissertations

We are facing an aging crisis, with 20% of the U.S. population projected to be geriatric (65+) by 2030 and live another 40+ years. Age-related diseases accompany a growing geriatric population, emphasizing the need to understand their etiology. Environmental pollutants compound this crisis by: 1) geriatrics are more susceptible, exacerbating age-related diseases and comorbidities, and 2) they accelerate biological aging, inducing age-related diseases at younger ages. We address this crisis using a ‘toxic aging coin’ approach; heads examines how age impacts toxicity, tails examines how chemicals accelerate aging. This thesis applies the heads side for Cr(VI)-induced neurotoxicity across ages. We …

Connectivity Of Amygdala Somatostatin-Expressing Neurons And Their Role In Taste-Guided Behavior., Jane Jeruto Bartonjo

Electronic Theses and Dissertations

The nucleus of solitary tract (NST) and parabrachial nucleus (PBN) represent the first and second central synapses of ascending gustatory information. Neural processing in these nuclei is influenced by descending input from forebrain regions such as the central nucleus of the amygdala (CeA). In mice, we have shown that somatostatin (Sst) expressing neurons of CeA that project to NST and PBN are largely distinct cell populations and optogenetic inhibition of the CeA/Sst-to-NST subpopulation increases the intake of high concentrations of quinine with no apparent effect on sucrose intake. Synaptic connectivity of these cells is needed to understand the possible mechanisms …

The Reinforcement Enhancing Effects Of Delta-9-Tetrahyrdrocannabinol (Thc) In Male And Female Rats, Kynah Walston

Electronic Theses and Dissertations

Cannabis is widely consumed by humans for pharmacological effects that are mediated by THC, though there is little evidence that THC is a primary reinforcer in non-human animal models. We hypothesized that THC may have potent reinforcement enhancing effects, comparable to other drugs (e.g., nicotine and caffeine) which are also widely consumed by humans, but difficult to establish as primary reinforcers in non-humans. In three experiments with male and female rats saccharin (SACC) or a visual stimulus (VS) served as reinforcers for operant behavior. We explored several pharmacological parameters of THC on responding for SACC or VS, including THC dose, …

Genetic Determinants Of Primary Nociceptor Sensitivity In Drosophila Melanogaster, Christine Hale

Electronic Theses and Dissertations

Abnormal pain affects ~50 million adults nationwide. With many of the current treatment options for chronic pain, such as opioid analgesics, carrying side effects such as the threat for addiction, research into safer and more effective options for chronic pain relief is crucial. Abnormal alterations in nociceptive sensitivity, which is the sensitivity of peripheral sensory neurons that detect noxious stimuli, can underlie, and perpetuate chronic pain. However, much is still unknown about the mechanism of how these abnormal alterations in sensitivity occur. To help elucidate genetic components controlling nociceptive sensitivity, the Drosophila melanogaster larval nociception model has been used …

Neural Stem Cells: Age-Dependent Outcomes During Viral Infections In The Central Nervous System, Manisha N. Chandwani

Electronic Theses and Dissertations

Viral infections in the central nervous system (CNS) are associated with neurodevelopmental and neurobehavioral deficits. The outcomes of viral infections can be driven by damage and death of neurons. Neural stem cells (NSCs) play key roles in neurodevelopment, repair, and physiological brain function. During a viral infection, NSC activity can disturbed by direct infection of NSCs by the virus or by anti-viral immune response. Here, we aimed to assess whether the anti-viral immune response can impact NSC activity during an immunocompetent response in the adult brain. We utilized a transgenic mouse model of Measles virus infection where only the CNS …

Sex-Specific Effects Of Chaperone And Glial Defenses On Experimental Lewy Body Disease, Tarun Bhatia

Electronic Theses and Dissertations

Lewy body disorders are a group of neurodegenerative conditions characterized by the pathological misfolding and aggregation of the abundant protein, α-synuclein. The most common Lewy body disorders are Parkinson’s disease and dementia with Lewy bodies. Apart from ageing, male sex is a major risk factor for Lewy body disorders, as men are at ~1.5-fold higher risk for these diseases than women. Yet, preclinical studies on Lewy body disorders rarely examine sex as a biological variable, and the mechanisms underlying sex-skewedness in disease risk remain undetermined.

Here, we developed a sex-stratified model of Lewy body disorders by exposing primary neurons harvested …

Behavioral Effects And Neurobiological Mechanisms Of 3-Aminobenzimide In A Rodent Model Of Chronic Psychological Stress, Liza Wills

Electronic Theses and Dissertations

Major depressive disorder (MDD) is a leading cause of disability worldwide, with a lifetime prevalence rate of approximately 20%. Inadequate pharmacological treatment methods for MDD are a significant debilitating factor. Patient estimates suggest that the treatment resistance rate for pharmacological interventions is over 30%. Postmortem analyses of human tissue of individuals diagnosed with MDD have shown an increase in Poly (ADP-ribose) polymerase 1 (PARP-1) mRNA gene expression in prefrontal cortical white matter when compared to psychiatrically normal brain tissue. In order to further investigate this issue, the present study used the social defeat stress/chronic unpredictable stress (SDS + CUS) rodent …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Beyond The Brain: A Study Of Α-Synuclein's Role In Bone And Adipose Tissue, Carolina A. Figueroa

Electronic Theses and Dissertations

α-Synuclein is a polypeptide encoded by the Snca gene, highly expressed in neurons, but it is also found in bones and adipose tissue. Co-expression analysis showed that Snca regulates skeletal homeostasis, and its deletion reduced estrogen deficiency-induced bone loss and weight gain. It is a major component of Lewy bodies (LB) in Parkinson’s disease (PD), leading to progressive immobilization and a range of nonmotor symptoms, including osteopenia, body composition alterations and insulin resistance. This thesis aimed to determine α-Synuclein’s intrinsic role in bone and adipose homeostasis. We discussed the PD pathophysiology emphasizing aspects of bone health and metabolism. By using …

Alcohol Consumption In A Preclinical Model Of Schizophrenia, Liza Hernandez

Electronic Theses and Dissertations

Schizophrenia is a debilitating psychiatric disorder that affects approximately 1% of the global population. Schizophrenia is highly comorbid with other psychiatric disorders such as Alcohol Use Disorder (AUD) with a prevalence rate of 27% - 65%, which is significantly higher than AUD exhibited by the general population (6%). Research indicates that a higher rate of AUD in individuals suffering from schizophrenia may be related to the common neuronal pathways that underlie the expression of both disorders. The present study will determine whether the neonatal quinpirole (NQ) rodent model of schizophrenia will approximate the human condition and exhibit increased EtOH consumption. …

The Role Of Inter-Enlargement Propriospinal Neurons In Locomotion Following Spinal Cord Injury., Courtney Therese Shepard

Electronic Theses and Dissertations

The focus of this dissertation is to explore the functional role of two anatomically-defined pathways in the adult rat spinal cord before and after spinal cord injury (SCI). To do this, a Tet^On dual virus system was used to selectively and reversibly silence neurons with cell bodies at spinal segment L2 and projections to spinal segment C6 (long ascending propriospinal neurons, LAPNs) and neurons that originate in the C6 spinal segment and terminate at L2 spinal segment (long descending propriospinal neurons, LDPNs). This dissertation is divided into five chapters. Chapter One provides background information regarding spinal cord injury, locomotion, …

Characterization Of Ethanol-Related Phenotypic Differences Between C57bl/6j And C57bl/6nj Substrains: Role Of Cyfip2?, Matthew C. Hartmann

Electronic Theses and Dissertations

The C57BL/6 (B6) mouse is the most commonly used inbred strain in biomedical research, and has served as the basis for various large-scale genetic and genomic projects. Although the parental substrain, C57BL/6J (B6J), originated at The Jackson Laboratory, isolated breeding colonies are now maintained at numerous sites. This separation has resulted in genetic drift that has led to the emergence of phenotypic differences among these colonies. For instance, B6J mice display higher levels of voluntary ethanol consumption and increased locomotor responses to psychostimulants, relative to C57BL/6N mice (B6N). Initial progress has been made in elucidating the genetic bases of these …

The Effects Of Two Novel Anti-Inflammatory Compounds On Prepulse Inhibition And Neural Microglia Cell Activation In A Rodent Model Of Schizophrenia, Heath W. Shelton

Electronic Theses and Dissertations

Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits …

Preference For Odor-Taste Mixtures Is Dependent On Previous Experience., Kelsey Allison Mcqueen

Electronic Theses and Dissertations

The perception of flavors occurs when a tastant is simultaneously detected and associated with an odorant (i.e., odor-taste mixture). Sampling an odor and taste together results in a congruent odor-taste mixture. Mixing an odor and taste from different congruent odor-taste pairs results in incongruent odor-taste mixtures. Creation of a flavor percept requires sampling a novel chemosensory stimulus; however, mammals exhibit robust neophobic behavior when presented with new chemosensory stimuli. To determine preferences for novel odorants and experienced odor-taste mixtures, we employ a two-bottle brief-access preference task where two chemosensory stimuli are presented simultaneously. We found that rats show a preference …

Behavioral And Molecular Analysis Of Memory In The Dwarf Cuttlefish, Jessica M. Bowers

Electronic Theses and Dissertations

Complex memory has evolved because it benefits animals in all areas of life, such as remembering the location of food or conspecifics, and learning to avoid dangerous stimuli. Advances made by studying relatively simple nervous systems, such as those in gastropod mollusks, can now be used to study mechanisms of memory in more complex systems. Cephalopods offer a unique opportunity to study the mechanisms of memory in a complex invertebrates. The dwarf cuttlefish, Sepia bandensis, is a useful memory model because its fast development and small size allows it to be reared and tested in large numbers. However, primary literature …

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 …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

Role Of Trkb-Signaling In Taste Development And Function., Jennifer Rios-Pilier

Electronic Theses and Dissertations

In the geniculate ganglion, taste neurons likely differentiate into subtypes during development, but very little is known about how these neurons are defined molecularly or how they differentiate. Embryonically, geniculate neuron development is regulated by the growth factor, brain ­derived neurotrophic factor (BDNF). Postnatally, BDNF becomes restricted to subpopulations of taste receptor cells with specific functions, primarily sour responding. I hypothesized that during development, the receptor for BDNF, tropomyosin kinase B receptor (TrkB), also becomes restricted to a neuronal subset. I used transgenic mouse models to label and quantify both geniculate sensory neurons (Phox2b+), and those expressing TrkB (GFP) across …

Examining The Associative Learning And Accumbal Dopaminergic Mechanisms Of Caffeine Reinforcement, Curtis Bradley

Electronic Theses and Dissertations

Caffeine is the most consumed psychoactive substance in the world, and most caffeine consumption in coffee and energy drinks is intended to produce a psychoactive effect. However, caffeine is not a primary reinforcer in preclinical paradigms – non-human species do not reliably take the drug to produce a psychoactive effect. However, caffeine is a ‘reinforcement enhancer’ in preclinical models; the effects of caffeine increase the motivation to obtain other non-drug reinforcers. The overall goal of this project was to determine if these reinforcement enhancing effects of caffeine could promote caffeine self-administration and to subsequently investigate the behavioral and neurochemical underpinnings …

Diel Rhythmicity Found In Behavior But Not Biogenic Amine Levels In The Funnel-Web Spider Agelenopsis Pennsylvanica (Araneae, Agelenidae), Alexander E. Demarco

Electronic Theses and Dissertations

Quantifying individual differences in behavior and the extent that behavior is influenced by circadian control is of paramount importance in behavioral ecology. In addition, the proximate mechanisms underlying behavior are also critical in order to obtain a more complete picture of how behavior evolves. Biogenic amines (BAs) are simple nitrogenous compounds derived from amino acids and have been consistently and extensively linked to behavior. For this study, we analyzed temporal patterns of BAs in relation to the antipredator (boldness) and aggressive behavior in female Agelenopsis pennsylvanica, a funnel-web spider. Using HPLC-ED, we compared behavioral responses to temporal patterns of …

An Analysis Of Neurogenesis In A Mouse Model Of Chemotherapy Related Cognitive Impairment, Maxwell A. Hennings

Electronic Theses and Dissertations

Cancer patients treated with adjuvant chemotherapy often experience cognitive decline following treatment. This phenomenon, often dubbed “chemo brain” or “chemo fog” is usually temporary, but for a subset of survivors, these cognitive impairments can be long-lasting (>10 years) and negatively affect patients’ quality of life, career performance, and social fulfillment. While it is unclear what neurobiological mechanisms underlie chemotherapy related cognitive impairment, the majority of the animal literature has focused on adult neurogenesis. One process important for neurogenesis is the proliferation of new neurons within the dentate gyrus of the hippocampus. It is evident that many chemotherapy agents can …

Therapy Dogs And The Impact On Employees In The Pediatric Medical Setting, Laine Foith

Electronic Theses and Dissertations

More than 40% of nurses reported experiencing significant burnout. Burnout is characterized by disengagement, cynicism, negative views of personal accomplishment and ability, and emotional exhaustion. The healthcare providers that experience burnout can possibly expect a decrease in ability to recognize/report errors, increase of negative feelings toward the patient, and decrease levels of patient satisfaction (Ernest, 2014). One of the ways Schub (2015) suggested to regulate burnout for employees was to provide psychosocial support to colleagues to reduce stress. This study is one of the first attempts to bridge the gap between the unknown correlation between qualitative and quantitative benefits of …

Exploring The Relationship Between Behaviour And Neurochemistry In The Polyphenic Spider, Anelosimus Studiosus (Araneae: Theridiidae), Jennifer B. Price

Electronic Theses and Dissertations

The importance of social behaviour is evident in human society, but there are both costs and benefits associated with cooperation and sociality throughout the animal kingdom. At what point do the benefits outweigh the costs, and when do selective pressures favour sociality and colonization over solitude and independence? To investigate these questions, we have focused on an anomalous species of spider, Anelosimus studiosus, also known now as the northern social spider. Throughout its broad range, A. studiosus is solitary and aggressive, but recently, colonies of cooperative and social individuals have been observed at northern latitudes. This leads to two …

An Analysis Of The Interaction Of Methylphenidate And Nicotine In Adolescent Rats: Effects On Bdnf, Elizabeth D. Freeman

Electronic Theses and Dissertations

This investigation was an analysis of the interaction of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine sensitization and conditioned place preference (CPP) in a rodent model and underlying mechanisms of this effect. Animals were treated IP with 1 mg/kg MPH or saline using a ―school day‖ regimen of five days on, two days off, from postnatal day (P) 28-50. During the final two weeks of MPH treatment, animals were either behaviorally sensitized to nicotine (0.5 mg/kg free base) or saline for 10 days, or conditioned to nicotine or saline using the CPP behavioral paradigm. In addition, three …

Neurochemical Levels Correlate With Population Level Differences In Social Structure And Individual Behavior In The Polyphenic Spider, Anelosimus Studiosus., Jennifer Bryson Price

Electronic Theses and Dissertations

Anelosimus studiosus is a socially polyphenic spider. Individuals can be classified as social/tolerant or solitary/aggressive. These behavioral differences are associated with considerable variation in social structure. Here, we begin to examine the physiological differences that may underlie the behavioral dimorphism in this species and possible implications for the evolution of sociality. Octopamine is a neurotransmitter that has been found to elevate aggression in invertebrates. Serotonin has been shown, in some cases, to interact antagonistically with octopamine. We used High Pressure Liquid Chromatography with Electrochemical Detection to quantify levels of these neurochemicals among adult females from social (multi-female) and solitary (single-female) …