Behavioral Neurobiology Commons^™

Perinatal Inflammation And Oxidative Stress Alter Adult Rat (Rattus Norvegicus) Motor Behavior, Alexander Young

Honors College Theses

Recent evidence in comparative animal models suggests that early life exposure to elevated inflammation (via LPS exposure) and oxidative stress (via acetaminophen exposure) may synergistically interact to alter typical neurodevelopmental trajectories, resulting in lasting effects on both behavior and gut-brain neurochemistry. The current study observed emotional and motor behaviors and collected fecal-boli to measure Tyrosine (TE) levels in male and female Long-Evans (Rattus norvegicus) rats. Subjects were either treated with [1] saline [2] lipopolysaccharide (LPS) to introduce an inflammatory state, [3] acetaminophen (APAP) to introduce oxidative stress, or [4] a dual-hit of both LPS + APAP on postnatal day (PD) …

The Sonic Hedgehog Effector Smoothened Modulates Cholinergic Interneuron Activity, Physiology, And Striatum-Dependent Behaviors, Santiago Uribe-Cano

Dissertations, Theses, and Capstone Projects

The striatum is a central node in action selection and associative learning, integrating cortical, thalamic, and neuromodulatory input. Among its principal modulators, dopamine (DA) and acetylcholine (ACh) are known for their temporally coordinated yet mechanistically distinct influences on striatal output. However, the upstream signals that regulate their dynamic interplay, particularly within cholinergic interneurons (CINs)—the primary source of striatal ACh—remain incompletely characterized. This dissertation investigates the role of Smoothened (Smo), a G protein-coupled receptor (GPCR) effector of Sonic Hedgehog (Shh) signaling, in modulating ACh signaling dynamics in the striatum.

Building on evidence that midbrain DA neurons co-release Shh and that CINs …

Neurochemical Signaling Of Reward-Based Learning In Ventral Tegmental Area Dopamine Neurons, Kyla F. Wholley

Dissertations, Theses, and Capstone Projects

Ventral tegmental area (VTA) dopamine neurons signal and participate in reward-related learning. Specifically, dopamine is postulated to encode reward-related environmental stimuli to compute reward prediction errors (RPEs). It is through the computation and maintenance of RPEs that learning occurs. However, little is known about the neural mechanisms that underlie how dopamine neurons compute RPEs and facilitate reward-related learning. The present study utilized fiber photometry in conjunction with a Pavlovian reward-based task to identify how GABA inputs to VTA dopamine neurons contribute to the computation of RPEs and reward-based behavior. Activity of GABA inputs to VTA dopamine neurons increased for reward-predicting …

Identification And Delineation Of Neuronal Pathways Underlying Hypophagia, Jing Cai

Dissertations and Theses (Open Access)

In terms of metabolism, eating disorders manifest in two extreme directions: overnutrition, which can lead to obesity, and malnutrition, which can result in underweight or even starvation. Both extremes compromise the quality of life. According to the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) standard, eating disorders affect up to 17.9% of young women and 2.4% of young men. Although eating disorders are primarily defined as mental disorders rather than metabolic disorders, they are intertwined with complex emotions and sensory perceptions. However, in contemporary animal research related to eating disorders and feeding behaviors, the majority of neuroscientists still examine …

Local Field Potentials In The Male Rat Nucleus Accumbens During Effort-Based Behavior, Celine Aliko, John Salamone, Alev Ecevitoglu

Honors Scholar Theses

Major depression is a devastating disorder that consists of multiple symptoms such as low mood and motivational dysfunction. It has been shown that motivational dysfunction can be studied in animal models by using effort-based choice paradigms, which vary in their response requirements. It has been reported that dopamine depletion in the nucleus accumbens decreases ratio-scheduled lever-pressing in a manner related to the size of the ratio requirement. One dopamine depleting agent is tetrabenazine (TBZ), which has been shown to decrease lever-pressing and induce low-effort bias. The current study aims to investigate behavioral and electrophysiological changes that occur with animals performing …

Role Of Nucleus Accumbens Dopamine Receptor Signaling In The Suppression Of Punished Reward Seeking, Grace M. Joyner, Anna Caroline Toburen

Senior Theses

Previous studies have shown that within the nucleus accumbens (NAc), a brain region associated with motivation and reinforcement learning, activity of neurons expressing the dopamine D2 receptor (D2R neurons) act as a “break” on risky behavior associated with negative outcomes. Moreover, when these neurons are stimulated, rats were found to become more risk averse. However, the impact of dopamine signaling through NAc D2R neurons in risk avoidance is still unclear. To further explore the role of NAc dopamine signaling in punished reward-seeking, we tested rats in a novel punished food-seeking paradigm in which subjects are trained to choose between a …

A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing

Dissertations, Theses, and Capstone Projects

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of co-administration of a D1-recepter partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a ‘conflict’ model of abstinence and cue-induced relapse. Rats were first trained to press a lever to self-administer heroin and drug delivery was paired contingently with cues (e.g., …

Contributions Of Reward Identity And Time Prediction Errors To Pavlovian Learning, Daniel B. Siegel

Dissertations, Theses, and Capstone Projects

Some models of associative learning attempt to explain effects such as blocking and unblocking as reflecting a prediction error (PE): Associative strength, and thereby learning, are said to be greater when the unconditioned stimulus (US) received following a cue deviates from one’s expectations. Some models of PE-motivated behavior and PE-relevant brain activity represent the US as a single quantitative variable for outcome value, and that learning therefore only occurs when outcome value differs from expectations. There is growing evidence to suggest that changes in other dimensions of reward, such as identity and timing, also contribute to learning. In Experiment 1, …

Estrogen Modulation Of Vta Dopamine Neuron Physiology And Behavioral Responsivity To Variable Social Stressors, Mary R. Shanley

Dissertations, Theses, and Capstone Projects

The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific …

Elucidating The Modulatory Role Of Dopamine In The C. Elegans Chemosensory Ash Neuron, Cory Kunkel

Electronic Theses, Projects, and Dissertations

The neurotransmitter dopamine regulates chemosensory avoidance behavior in the model organism Caenorhabditis elegans. Avoidance behaviors are mediated by the polymodal ASH nociceptive sensory neurons, and behavioral avoidance of stimuli detected by ASH is less robust when dopamine signaling is impaired. We are investigating the neural response of the ASH neurons to various stimuli; our investigation includes the behavioral and physiological responses from the ASH neurons as dopamine signaling is manipulated to better understand the effects of dopamine on these sensory neurons. We hypothesize that dopamine plays a regulatory role on the ASH neurons, lessening the response of the ASH …

The Development And Evaluation Of Novel Da Transport Inhibitors And Their Effects On Effort-Related Motivation: A Review, Mukund Desibhatla

Honors Scholar Theses

Depression is a debilitating disorder that can cause motivational deficits such as psychomotor retardation, anergia, apathy, and fatigue. Recent research indicates that these motivational deficits, and potential pathways of therapeutic intervention, can be studied in animal models involving rats and mice. Treatments with the VMAT-2 inhibitor tetrabenazine (TBZ) and cytokine interleukin-1ß (IL-1ß) can create a low-effort bias and impair effort-related motivation (Nunes et al. 2013, 2014). A number of high-affinity DA transport inhibitors such as d-amphetamine, methylphenidate, and cocaine can restore extracellular DA, albeit with the cost of undesirable effects such as high abuse liability. These observations have led researchers …

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution …

Sleep Modifications In A Drosophila Melanogaster Model Of Fragile X Syndrome, Morgan Mclaughlin

Undergraduate Honors Theses

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disabilities, disruptions in sleep, and autism in humans. Mutations in Fragile X Mental Retardation gene 1 (FMR1), which codes for a protein that modifies the expression of many target proteins, are primarily responsible for this disorder. Genetic modifications of FMR1 can increase or decrease the overall amount of sleep in humans. A potential pharmaceutical target of FXS is dopamine, a critical neurotransmitter in the regulation of sleep and wakefulness. In fruit flies (Drosophila melanogaster) dopamine has been shown to alter sleep. The mushroom body, a structure in …

The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers

Undergraduate Honors Theses

Understanding the neural processes that mediate decision making is a relatively new field of investigation in the scientific community. With the ultimate goal of understanding how humans decide between one path and another, simpler models such as Drosophila Melanogaster, the common fruit fly, are often utilized as a way of determining the neural circuits involved in these decision-making processes. One of the most important decisions flies make is the decision of where to lay their eggs (oviposit). Choosing the proper substrate upon which to lay eggs is a crucial decision that can ultimately impact their fecundity. This paper investigates the …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Murine Genetic Variance In Sugar And Fat-Conditioned Flavor Preferences: Roles Of Dopamine, Opioid And Nmda Receptors And Nutritive Sensing, Tamar T. Kraft

Dissertations, Theses, and Capstone Projects

As obesity and diabetes have emerged as a severe public health crisis, understanding the mechanisms underlying the consumption of sugars and fats has become a topic of vigorous study. From a biological standpoint, genetic dispositions, neurochemical and hormonal influences, and predetermined orosensory and postingestive signals that modulate the hunger and satiety process may govern physiological aspects of the obesity puzzle. In addition to an innate appetite and attraction for simple carbohydrates and fats, learning plays an important role in modulating preferences for sugar- and fat-rich foods in rodents, including inbred mouse strains. Marked genetic variance has been observed among murine …

Basal Ganglia Involvement In The Playfulness Of Juvenile Rats, Stephen M. Siviy

Psychology Faculty Publications

Play is an important part of normal childhood development and can be readily studied in the laboratory rat in the form of rough‐and‐tumble play. Given the robust nature of rough‐and‐tumble play, it has often been assumed that the basal ganglia would have a prominent role in modulating this behavior. Recent work using c‐fos expression as a metabolic marker for neural activity combined with temporary inactivation of relevant corticostriatal regions and pharmacological manipulations of opioid, cannabinoid, and dopamine systems has led to a better understanding of how basal ganglia circuitry may be involved in modulating social play in the juvenile rat. …

Comparative Role Of Reward In Long-Term Peer And Mate Relationships In Voles, Nastacia L. Goodwin, Sarah A. Lopez, Nicole S. Lee, Annaliese K. Beery

Neuroscience: Faculty Publications

This is a contribution to SI: SBN/ICN meeting. In social species, relationships may form between mates, parents and their offspring, and/or social peers. Prairie voles and meadow voles both form selective relationships for familiar same-sex peers, but differ in mating system, allowing comparison of the properties of peer and mate relationships. Prairie vole mate bonds are dopamine-dependent, unlike meadow vole peer relationships, indicating potential differences in the mechanisms and motivation supporting these relationships within and/or across species. We review the role of dopamine signaling in affiliative behavior, and assess the role of behavioral reward across relationship types. We compared the …

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 …

Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa

Master of Science in Integrative Biology Theses

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like …

Possible Breakdown Of Dopamine Receptor Synergism In A Mouse Model Of Huntington's Disease, Samantha F. Kennedy

LSU New Orleans Theses and Dissertations

The model of basal ganglia function proposed by Albin, Young and Penney (1989) describes two anatomically independent motor pathways, the direct and indirect. However, under normal conditions striatal dopamine (DA) is required for the expression of motor behavior, and DAergic control of the two pathways (via D1 and D2 receptors, respectively) is dependent on co-activation. We tested for a possible breakdown of D1/D2 synergism using transgenic R6/1 mice bearing the human huntingtin allele (Htt). Motor stereotypy, observed prior to the onset of HD-related symptoms, was rated on a 5-point scale following activation of: A) D1 receptors alone, B) D2 receptors …

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 …

Distribution And Activation Of Catecholaminergic Neurons In The Brain Of Male Plainfin Midshipman Fish: Divergence In Behavior And Reproductive Phenotype, Zachary Ghahramani

Dissertations, Theses, and Capstone Projects

The plainfin midshipman fish, Porichthys notatus, provides an excellent opportunity for delimiting the influence of neurochemical content on vertebrate vocal behavior, in part because the production and recognition of social-acoustic signals is vital to their reproductive behavior. There are two distinct reproductive male morphs that follow divergent developmental trajectories with corresponding alternative reproductive tactics: type I males are the territorial/nesting morph that vocally court females during the summer breeding season while type II males do not court females, but instead sneak spawn in competition with type I males. Catecholaminergic neurons, which synthesize and release the neurotransmitters dopamine or noradrenaline, …

Examining The Neuronal Dopaminergic Pathway Underlying Sleep Behavior And Related Dopamine Sleep Disorders, Mary Beth Putz

Undergraduate Honors Theses

The human brain is an extremely complex organ with approximately 100 billion different neurons that are constantly sending and receiving messages. These messages are sent using the chemical messengers of the brain: neurotransmitters and neuromodulators. Mechanisms of neural control of sleep are substantially conserved across species. Evidence from multiple animal models including flies, zebrafish, and mice shows that the arousal, or wake phase, is regulated by conserved neuromodulators such as dopamine, norepinephrine, and serotonin. Since these neurotransmitter systems are distributed throughout the brain and sub-serve many functions in addition to sleep, the precise circuit mechanisms by which these neurotransmitters regulate …

Testing The Efficacy Of Lsn2463359, A Metabotropic Glutamate 5 Receptor Positive Allosteric Modulator, In Animal Models Of Schizophrenia, Dierdre M. Freamon

Seton Hall University Dissertations and Theses (ETDs)

For many years the dominant theory surrounding the cause of schizophrenia was focused on elevated dopamine levels found in critical areas of the brain. Recently a new theory has emerged pointing to elevated glutamate levels resulting from hypofunction of NMDA receptors and hypoactivity of GABAergic neurons which normally inhibit glutamatergic cells in a tonic manner. Therefore, while traditional antipsychotics directly block dopamine receptors, some of the newly generated compounds are designed to modulate glutamate to normal levels.

I propose testing the efficacy of the metabotropic glutamate 5 receptor modulator LSN2463359, previously shown to act as an indirect agonist of the …

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

Chronic Ethanol Exposure Causes Disinhibited Behavior In Drosophila, Estrella Padilla, Kyung-An Han

COURI Symposium Abstracts, Summer 2012

Ethanol consumption is frequently associated with disinhibited sexual and locomotor behaviors in humans. Dopamine, a major monoamine found in vertebrates and invertebrates, is implicated in these processes since it regulates motivation, reward, motor control, and sexual behaviors. The goal of this study is to elucidate the role of dopamine in ethanol-associated behavioral disinhibition using the genetically tractable model system Drosophila melanogaster. Previous studies have shown a requirement for normal dopamine neurotransmission for ethanol-induced courtship disinhibition. Furthermore, genetic manipulation of the dopamine system revealed that D1 receptor activity is important for disinhibition and D2 for sensitization. The current study focuses …

Ethanol Reward Conditioning In Drosophila Melanogaster, Isaac A. Moya^, Young-Cho Kim, Kyung-An Han*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Validation On Sodium Channel Dependence By Electrical Stimulation-Induced Dopamine Release, Alice E. Hernandez ^, Mabel N. Terminel, Edward Castaneda *

COURI Symposium Abstracts, Spring 2012

No abstract provided.

The Effects Of Extended Access To Methamphetamine Self-Administration On Dopaminergic Markers In The Striatum, Joe Luevano

Open Access Theses & Dissertations

Methamphetamine (METH) abuse is a persistent problem in the U.S. and abroad. Escalation of METH use among independent users occurs for a variety of physiological and psychological reasons. Methamphetamine dependence may be attributed to the rewarding effect of this drug via the dopaminergic systems of the central nervous system (CNS). The presence of METH in the CNS increases synaptic release of dopamine. This increase in dopaminergic neurotransmission is thought to be directly attributed to the rewarding effects of METH. Following METH use, compensatory changes have been found to occur in the dopaminergic system during various periods of abstinence. It is …