Neuroscience and Neurobiology Commons^™

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 …

The Relationship Between Sleep, Working Memory, And Decision Making In Young And Old Adult Populations, Melissa G. Merz

Honors Undergraduate Theses

Sleep is known to influence basic tasks concerning working memory, reaction time and executive functioning (Silva, Wang, Ronda, Wyatt, & Duffy, 2010; Nebes, Buysse, Halligan, Houck, & Monk, 2009). However, the amount that sleep influences these functions varies from study to study possibly due to differences in age and task design. Aim 1A of this study is to determine if sleep quality affects working memory. Aim 1B of this study is to determine if age affects sleep quality and working memory in comparison of young and old adult populations. Finally, Aim 2 of this study is to determine if there …

N-Alkyl 4-Methylamphetamine Enantiomers And The Implication For Potential Modulation Of Abuse Liability And Enhancement Of Psychoactive Drug Targeting., Ramsey Sitta

Theses and Dissertations

Drugs of abuse have a long history in humanity. Currently however, a subject of great interest is the phenylalkylamine family of drugs. Not only is the abuse liability of interest but also the potential therapeutic expansion of the capabilities of this family of drugs by utilizing the unique stereospecific effects of the newly discovered hybrid compounds. Based upon prior data of N-Alkyl 4-MA the enantiomers of N-Methyl, N-Ethyl, and N-Propyl were analyzed in hDAT, hNET, and hSERT. It was found that there was a negative correlation between chain length and potency and dopaminergic component. In agreement with the currently established …

Octopamine In Sexual Behavior, Ana Isabel Fernandez

Open Access Theses & Dissertations

Octopamine is a biogenic amine neuromodulator present in neuronal and non-neuronal tissues in invertebrates (Roeder, 1999). It modulates numerous physiological processes such as motivation, pheromone response, olfaction, ovulation, learning and memory. Octopamine together with its precursor tyramine have roles restricted only to invertebrates (Roeder, 1999). It is believed that octopamine is the invertebrate homolog of norepinephrine, a catecholamine present in mammals that acts as a neuromodulator in the sympathetic and central nervous systems. Both octopamine and norepinephrine are derived from the same amino acid tyrosine and are monoamine neurotransmitters. The main objective of this study is to understand the role …

A Behavioral And Neuroimmune System Model Of The Effects Of Chronic Low-Level Lead Exposure In Young Male C57bl/6j Mice, Mayra Gisel Flores-Montoya

Open Access Theses & Dissertations

Chronic low-level lead exposure reduces memory in children however the brain mechanisms mediating these effects are not known. In previous studies we showed that early lead exposure reduced olfactory memory and exploratory behavior in young mice, and reduced microglia cell density in hippocampus/dentate gyrus. The present studies aimed to identify additional behavioral tests that were sensitive to early low-level lead exposure in young mice; and to examine whether microglia upregulated factors known to promote cell migration. Seventy-two C57BL/6J male mice were exposed to 0 ppm (controls), 30 ppm (low-dose), or 430 ppm (high-dose) of lead acetate via dams' milk from …

Effects Of Chromium On Mouse Splenic T Lymphocytes And Effects Of Ethanol Exposure During Early Neurodevelopment On Behaviors In Mice, Lu Dai

Theses and Dissertations--Toxicology and Cancer Biology

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively.

Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro …

Identification Of Novel Sleep Related Genes From Large Scale Phenotyping Experiments In Mice, Shreyas Joshi

Theses and Dissertations--Biology

Humans spend a third of their lives sleeping but very little is known about the physiological and genetic mechanisms controlling sleep. Increased data from sleep phenotyping studies in mouse and other species, genetic crosses, and gene expression databases can all help improve our understanding of the process. Here, we present analysis of our own sleep data from the large-scale phenotyping program at The Jackson Laboratory (JAX), to identify the best gene candidates and phenotype predictors for influencing sleep traits.

The original knockout mouse project (KOMP) was a worldwide collaborative effort to produce embryonic stem (ES) cell lines with one of …

Characterization Of Sex Differences In The Reinforcing Effects Of Nicotine, Rodolfo Jesus Flores Garcia

Open Access Theses & Dissertations

It is presently unclear whether ovarian hormones, such as estradiol (E2) promote the reinforcing effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day procedure involving 2 days of vehicle administration and 2 days of E2 administration. Two doses of E2 (25 or 250 ug) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on …

Predatory Behavior And Neuroanatomy Of The Sessile Rotifer, Cupelopagis Vorax , Elizabeth Preza

Open Access Theses & Dissertations

Predator-prey interactions contribute to the evolution of behavioral and morphological characteristics of species. However, research on zooplankton has mainly focused on planktonic species such Mesocyclops edax (Arthropoda, Cyclopoida) and Asplanchna spp. (Rotifera, Ploima). Cupelopagis vorax (Rotifera, Collothecaceae) provides a unique model for studying the predatory behavior of a sessile species. Cupelopagis was chosen because it is the only rotifer known to exhibit rheotaxic behaviors in the presence of prey and because it undergoes indirect development where non-feeding, free-swimming larvae mature into feeding adults. The integration of behavioral techniques, immunohistochemistry, and confocal microscopy were used to provide insight as to how …

Canine Emotions As Seen Through Human Social Cognition, Miiamaaria V. Kujala

Animal Sentience

It is not possible to demonstrate that dogs (Canis familiaris) feel emotions, but the same is true for all other species, including our own. The issue must therefore be approached indirectly, using premises similar to those used with humans. Recent methodological advances in canine research reveal what dogs experience and what they derive from the emotions perceptible in others. Dogs attend to social cues, they respond appropriately to the valence of human and dog facial expressions and vocalizations of emotion, and their limbic reward regions respond to the odor of their caretakers. They behave differently according to the …

Sensory-Specific Satiety Is Intact In Rats Made Obese On A High-Fat, High-Sugar Choice Diet., Kevin P. Myers

Faculty Journal Articles

Sensory-specific satiety (SSS) is the temporary decreased pleasantness of a recently eaten food, which inhibits further eating. Evidence is currently mixed whether SSS is weaker in obese people, and whether such difference precedes or follows from the obese state. Animal models allow testing whether diet-induced obesity causes SSS impairment. Female rats (n = 24) were randomly assigned to an obesogenic high-fat, high-sugar choice diet or chow-only control. Tests of SSS involved pre-feeding a single palatable, distinctively-flavored food (cheese- or cocoa-flavored) prior to free choice between both foods. Rats were tested for short-term SSS (2 h pre-feeding immediately followed by 2 …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

Animal Sentience? Neuroscience Has No Answers, Yoram Gutfreund

Animal Sentience

Woodruff’s target article provides a detailed review of comparative studies on brain and behavior in teleosts. However, the relevance of the scientific data to the question of consciousness rests solely on the validity of a small set of so-called "requirements for consciousness." I use the target article to demonstrate that the neuroscientific study of animal consciousness in general relies on external, highly questionable and unfalsifiable criteria, and therefore fails to resolve the question of which animal species are sentient. Fish behavior can be remarkably complex, but whether fish are conscious remains a matter of belief.

Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton

Theses and Dissertations

Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Interleukin-17a Promotes Cd8 T Cell Cytotoxicity To Facilitate West Nile Virus Clearance, Amber M. Paul, Dhiraj Acharya, Penghua Wang, Jianfeng Dai, David Gate

Publications

CD8 T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a/) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 T cells isolated from Il17a/ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in …

Adult Neurogenesis In Avian Auditory Cortex, Caudomedial Nidopallium (Ncm): Lateralization And Effects Of Statins, Shuk C. Tsoi

Dissertations, Theses, and Capstone Projects

In the first part of this paper, we investigated the basic relationship between learning, memory and adult neurogenesis using zebra finches. We found that in the auditory cortex, the left hemisphere had more new neurons than the right hemisphere. This lateralization was correlated with song learning and memory. In the second part, we used juvenile zebra finches as a model organism to study the effects of Lipitor on learning, memory and neurogenesis. We found that Lipitor impaired song learning and memory storage. Lipitor treatments also changed the morphology of new neurons and size of old neurons, suggesting statins may affect …

The Evolutionary History Of Consciousness, Eirik Søvik, Clint Perry

Animal Sentience

Klein & Barron argue that insects are capable of subjective experience, i.e., sentience. Whereas we mostly agree with the conclusion of their arguments, we think there is an even more important message to be learned from their work. The line of reasoning opened by Klein & Barron proves instructive for how neuroscientists can and should explore the biological phenomenon of consciousness.

An Ultrasensitive Electrogenerated Chemiluminescence-Based Immunoassay For Specific Detection Of Zika Virus, Amber M. Paul, Dhiraj Acharya, Pradip Bastola, Linda Le, Estenfani Fernandez, Michael S. Diamond, Wujian Miao, Fengwei Bai

Publications

Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV-PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs …

An Investigation Of Short-Term Plasticity In Human Motor Cortex, Matthew Alan Gannon

Graduate Theses and Dissertations

Transcranial magnetic stimulation (TMS) produces a transient magnetic field that activates underlying cortical tissue by eliciting an electrical discharge of the neurons in the targeted area. Repetitive TMS (rTMS) uses patterns of repetitive TMS pulses and has been reliably shown to produce changes in the state of cortical excitability outlasting the time of stimulation. One such protocol that has demonstrated states of increased excitability is intermittent theta burst stimulation (iTBS). This method applies high-frequency bursts (50Hz) of pulses every 200 ms in trains of ten bursts. The effects of and differences between rTMS protocols have been investigated since gaining popularity …

Tnf Signaling During Tissue Damage-Induced Nociceptive Sensitization In Drosophila, Juyeon Jo

Dissertations and Theses (Open Access)

Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive sensitization in both Drosophila and vertebrates. In Drosophila larval model of nociceptive sensitization, UV irradiation in results in epidermal apoptosis and thermal allodynia. TNF/Eiger is produced from dying epidermal cells and acts its receptor in nociceptive sensory neurons to induce thermal allodynia. Inhibition of TNF signaling results in attenuation of nociceptive sensitization whereas epidermal apoptosis still occurs in the absence of TNF. Major gaps in this model are the precise relationship between apoptotic cell death and production of TNF/Eiger, downstream signaling mediators for TNFR/Wengen, and target genes that alter nociceptive …

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 …

Insects Have The Capacity For Subjective Experience, Colin Klein, Andrew B. Barron

Animal Sentience

To what degree are non-human animals conscious? We propose that the most meaningful way to approach this question is from the perspective of functional neurobiology. Here we focus on subjective experience, which is a basic awareness of the world without further reflection on that awareness. This is considered the most basic form of consciousness. Tellingly, this capacity is supported by the integrated midbrain and basal ganglia structures, which are among the oldest and most highly conserved brain systems in vertebrates. A reasonable inference is that the capacity for subjective experience is both widespread and evolutionarily old within the vertebrate lineage. …

The Contribution Of The Pineal Gland On Daily Rhythms And Masking In Diurnal Grass Rats, Arvicanthis Niloticus, Dorela D. Shuboni, Amna A. Agha, Thomas K. H. Groves, Andrew J. Gall

Faculty Publications

Melatonin is a hormone rhythmically secreted at night by the pineal gland in vertebrates. In diurnal mammals, melatonin is present during the inactive phase of the rest/activity cycle, and in primates it directly facilitates sleep and decreases body temperature. However, the role of the pineal gland for the promotion of sleep at night has not yet been studied in non-primate diurnal mammalian species. Here, the authors directly examined the hypothesis that the pineal gland contributes to diurnality in Nile grass rats by decreasing activity and increasing sleep at night, and that this could occur via effects on circadian mechanisms or …

Encoding Of Saltatory Tactile Velocity In The Adult Orofacial Somatosensory System, Rebecca Custead

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement.

High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable …

Assessment Of Daf-19 Related Behavioral Defects, Loraina A. Stinson

Lawrence University Honors Projects

The daf-19 gene encodes the only RFX transcription factors in C. elegans, producing at least four related protein isoforms, one of which, DAF-19C, is responsible for ciliogenesis. Previous work by Senti and Swoboda (2008) demonstrated that adult worms deficient in all four DAF-19 proteins have extremely aberrant dwelling and roaming behavior on bacterial food. Most intriguingly, the addition of cDNA encoding the DAF-19C isoform restores cilia formation, but does not fully restore wild-type dwelling and roaming behavior. We are suggesting that additional neuron functions are needed to properly execute behaviors and these neuron functions require the activity of other …

Examination Of Methamphetamine Reinstatement In Female And Male Rats: A Pre-Clinical Model Of Relapse, Steven T. Pittenger

Department of Psychology: Dissertations, Theses, and Student Research

Methamphetamine (meth) dependence is often characterized by persistent and chronic relapse (i.e., return to drug use). There is growing pre-clinical and human evidence suggesting females are at greater risk to relapse. The set of studies presented in this dissertation extended this limited evidence by identifying sex-dependent neural substrates correlated with meth-triggered reinstatement (Experiment 1) and by examining sex-differences in reinstatement triggered by drugs of abuse that are commonly co-abused with meth (Experiment 2). Female and male rats were trained to self-administer meth, received subsequent extinction sessions, and then tested for reinstatement. In Experiment 1, rats were perfused following reinstatement testing …

The Effects Of Lipopolysaccharide-Induced Neuroinflammation On Learning And Forgetting In Juvenile Rats, Michele Barry

Seton Hall University Dissertations and Theses (ETDs)

The inability to remember events experienced very early in life is referred to as Infantile Amnesia (IA) and has been observed in both humans and animals. Over the years interest in the phenomenon waned, but has recently increased with the discovery of new neurobiological methods to study brain function (e.g., Callaghan, Li & Richardson, 2014). The neurobiological mechanism behind IA has yet to be determined, but several innovative theories have been developed with these new research methods. The neurogenesis hypothesis theorizes that increased neurogenesis during early development disrupts previously established memories. The hippocampus, an area that mediates both the memory …

Reverse Genetic Screening Of Innexin Gap Junction Proteins In Drosophila Neurons, Shannon P. Fox

Senior Honors Projects, 2010-2019

The reflexive response and perception of pain (nociception) is an evolutionarily conserved process in animals. Pain can be a major health concern and current treatments often prove insufficient, especially in regards to chronic pain. Greater understanding of the molecular processes underlying pain sensation could lead to new and more effective treatments. The aim of this study is to investigate the molecular mechanisms of cold nociception in Drosophila melanogaster. A specific subset of peripheral sensory neurons (Class III dendritic arborization (da) neurons), are implicated in Drosophila larvae’s response to noxious cold.

Previous literature has associated a family of gap junction protein, …

The Effects Of Chronic Partial Sleep Deprivation And Chronic Voluntary Alcohol Consumption On Δfos B Accumulation, Kristian Ponder

Masters Theses, 2010-2019

The present study explores the relation between sleep restriction and alcohol use and the neural substrates that result from chronic behaviors. Accumulation of the transcription factors ΔFosB is suggested as a possible outcome of chronic behaviors, such as addiction. Sleep is discussed as possible mediating factor in the relationship between ΔFosB and chronic alcohol consumption. There were four experimental groups in this study: Control (C), Sleep Deprivation only (SD), Alcohol Exposure only (AO), and both sleep deprivation and alcohol exposure (B). Levels of ΔFosB accumulation in the Nucleus Accumbens (NAc) revealed a significant main effect of sleep deprivation, but no …