Neuroscience and Neurobiology Commons^™

Optimization Of Tyrosine Hydroxylase Antibody For Immunohistochemistry Fluorescence Detection In Zebrafish (Danio Rerio), Madison Thurber

Theses/Capstones/Creative Projects

Dopamine is an important neurotransmitter produced through the catecholamine synthesis pathway that affects brain activity. Unregulated dopamine levels can lead to various diseases such as Parkinson’s Disease or attention deficit hyperactivity disorder (ADHD). Optimization of an immunohistochemistry protocol will allow for the quantification of tyrosine hydroxylase antibody, which indirectly allows for dopamine quantification in dopaminergic regions within the brain. However, the antibody concentration to give the optimal signal-to-noise ratio in IHC varies across studies. Through this experiment, I determined the concentration of tyrosine hydroxylase (TyrH) antibody for immunohistochemistry that gave the best signal-to-background noise ratio within several known dopaminergic regions …

Effects Of Methamphetamine On Microglia Through Reactive Oxygen Species, Chase Seiter, Jordan Yorgason, Nathan Sheets, James Blood, Lydia Hawley, Erin Taylor, Eliza White, Hillary Wadsworth, Jason Hansen

Library/Life Sciences Undergraduate Poster Competition 2024

▪ Dopamine release in the Nucleus Accumbens (NAc) underlies motivational behavior for methamphetamine (METH) reward.

▪ ATP is a chemoattractant to microglia and is METH on ATP release and clearance are unknown.

▪ Furthermore, METH is known to produce reactive dopamine terminal function, microglia morphology and METH interactions are unknown.

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

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 & 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 …

Sex Differences In Mood And Anxiety-Related Outcomes In Response To Adolescent Nicotine Exposure, Tsun Hay Jason Ng

Electronic Thesis and Dissertation Repository

Nicotine dependence is causally linked to increased risk of mood/anxiety disorders in later life. Females are reported to experience a higher prevalence of anxiety/depressive disorders and challenges in smoking cessation therapies, suggesting a potential sex-specific response to nicotine exposure and mood/anxiety disorder risk. However, pre-clinical evidence of sex-specific responses to adolescent nicotine exposure is unclear. Thus, to determine any sex differences in anxiety/depressive-related outcomes, adolescent male and female Sprague Dawley rats received nicotine (0.4 mg/kg; 3x daily) or saline injections for 10 consecutive days, followed by behavioural testing, in-vivo electrophysiology and Western Blot analyses. Our results revealed that adolescent nicotine …

Utilizing Crispr Cas9 To Visualize Dopamine Receptors In Caenorhabditis Elegans, Lauren Michelle Velasquez

Electronic Theses, Projects, and Dissertations

Dopamine (DA) is a neurotransmitter with imperative implications in many functions including movement, reward, and cognition. Studying the pathways of dopaminergic neurons at multiple levels allows us to understand the ways in which these systems can go wrong. We study dopamine in a model system such as the worm Caenorhabditis elegans because of its relatively simple and well-characterized nervous system. DA is involved in regulating chemosensory behaviors in worms. The purpose of this research project is to definitively answer the following question: Are the dopamine receptors DOP-1 and DOP-4 expressed in chemosensory neurons? Previous reporter assays show that neither of …

Recovery From Social Isolation In Drosophila: The Role Of Dopamine And The Autism-Related Gene Nlg3., Ryley T. Yost

Electronic Thesis and Dissertation Repository

Within a group, individuals establish their preferred distance from each other, or social space, a form of social behaviour. The resulting distance depends on the exchange of social cues from others that needs to be perceived and integrated within the organism’s neural circuitry. In humans, social spacing can be impaired in neuropsychiatric disorders such as autism and schizophrenia. When organisms are subject to social isolation, profound changes in social behaviour are observed in a variety of species from insects to mammals, including social space. However, the genetic and molecular mechanisms modulating a behavioural response to isolation and possible recovery remain …

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 …

Variation In Sign-Tracking And Goal-Tracking Behaviors In A Genetically Diverse Inbred Panel Of Mice, Emily A. Schoenblum

Undergraduate Honors Theses

No abstract provided.

Connectional Analysis Of Brain Regions Associated With Feeding, Kenichiro Negishi

Open Access Theses & Dissertations

Rodent models are invaluable for understanding the foundations of motivatedbehaviors. One major obstacle faced by these efforts is the lack of a 'wiring diagram' or a 'parts list' of structures that support motivated behaviors. Here, I present work that advances our knowledge of the structural organization of connections and chemoarchitecture of the diencephalon. Chapter 1 aims to clarify a wiring diagram of the medial prefrontal cortex (mPFC) following a recent demonstration of cortically-evoked feeding through this region. Chapter 2 clarifies the distributions of a subpopulation of tyrosine hydroxylase (TH) neurons in the hypothalamus. These disparate datasets were analyzed and interpreted …

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 …

Quantifying Psychostimulant-Induced Sensitization Effects On Dopamine And Acetylcholine Release Across Different Timescales, Georg Lange

Dissertations, Theses, and Capstone Projects

Drug-induced behavioral sensitization describes the phenomenon that behavioral response to a drug of abuse is getting stronger if the same psychostimulant is delivered multiple times which is much more pronounced if done in the same environmental context. A proposed neural basis is the formation of an association between contextual cues and the rewarding drug which is mediated by dopamine. Dopamine operates at different timescales and to fully understand dopamine sensitization, it is necessary to investigate dopamine release at slow (tens of minutes) but also faster (sub-second) timescales. But creating a holistic view has been difficult due to a lack of …

Assessment Of The Triple Reuptake Inhibitor Diclofensine: Effort-Based Decision-Making In A Rodent Model Of Motivational Dysfunction, Sofia Papanikolaou

Holster Scholar Projects

Serotonin-selective reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications. Despite their popularity, they remain relatively ineffective at treating effort-related motivational symptoms of depression such as fatigue and anergia. Increasing research on triple reuptake inhibitors (TRIs) that target three neurotransmitters—dopamine, serotonin, and norepinephrine—has suggested that TRIs could have efficacy in targeting motivational dysfunction due to their dopaminergic effects. Previous research has shown that the dopamine depleting agent tetrabenazine can reliably induce motivational deficits in rats, as evidenced by a shift towards low-effort behavior in effort-based choice tasks, and provide a validated approach to creating a model of motivational dysfunction. …

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., …

The Neurobiological Underpinnings Of Depression-Related Maternal Behavior Deficits, Sarah B. Winokur

Doctoral Dissertations

Maternal caregiving is a dynamic process that requires extensive cognitive, motivational, and affective processing. World-wide, approximately 17% of mothers are diagnosed with postpartum depression yearly (Wang et al., 2021). Untreated, mothers with postpartum depression experience deficits in cognition, motivation, affect, and parenting (Arteche et al., 2011; Dix and Meunier, 2009; Lovejoy et al., 2000). Although postpartum depression is related to compromised parenting, to date, few studies have examined the neurobiological mechanisms by which maternal behavior is compromised in postpartum depression (Field, 2010; Murray et al., 1996)_. This dissertation aims to examine how depression neurobiologically disrupts parenting abilities. These studies …

Effects Of Catharanthine On Dopamine Release In The Nucleus Accumbens And Ethanol Consumption, Emily Baldwin

Undergraduate Honors Theses

This thesis discusses the history of catharanthine and related compounds, and their potential anti-addictive properties. Current research is exploring possible mechanisms of these properties. Past studies have found catharanthine has effects on neurons that project to the mesocorticolimbic system, an area implicated in addiction. We have seen that catharanthine decreases evoked dopamine (DA) release but increases basal DA release. This is the first study to investigate catharanthine’s effect on DA transmission in vivo. Using microdialysis, we determined the effect of catharanthine on DA in the nucleus accumbens of the striatum. This study determines the effect of different doses of …

Dopaminergic Modulation Of A Fast Visuomotor Pathway In Parkinson's Disease, Madeline C. Gilchrist

Electronic Thesis and Dissertation Repository

Parkinson’s disease (PD) is associated with reduced dopaminergic (DA) input to the dorsal striatum (DS). This study investigated the role of DA in modulating automatic, stimulus-driven reactions by assessing contextual control of stimulus-locked responses (SLRs) in 10 PD patients off and on DA medication. The SLR is the rapid recruitment of limb muscles that drives the arm towards suddenly appearing stimuli. Participants reached away from (anti-reach) or towards (pro-reach) a target on a screen, depending on instruction appearing 500 or 1000ms before target appearance. Modulation of SLRs was assessed by comparing SLR magnitude on anti- and pro-reach trials using surface …

Early Experience And The Functional Calibration Of The Stress-Response Systems, Niki Hosseini-Kamkar

Electronic Thesis and Dissertation Repository

Individuals exposed to adversities in childhood are at a greater risk of developing various diseases as adults, including cardiovascular disease and cancer (Felitti et al. 1998). These findings have sparked an interest in examining biological mechanisms that might explain the link between exposure to adversity and disease. To date, evidence has linked adversity to the function of the hypothalamic-pituitary-adrenal (HPA) axis. More recently, adversity has been associated with the function of the mesolimbic dopamine pathway as well.

This thesis uses a variety of techniques to explore the association between adversity and the function of the HPA axis and mesolimbic dopamine …

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 …

Cholinergic Modulation Of Behaviour, Ornela Kljakic

Electronic Thesis and Dissertation Repository

The cholinergic system is one of the most influential and essential signalling systems in the body. In the brain, cholinergic neurons innervate many brain regions where they influence a wide variety of behaviours. However, the precise role of each cholinergic region on distinct types of behaviour is not well known. Furthermore, in recent years there has been evidence that many cholinergic neurons in the brain have a capacity for co-transmission. Yet the functional significance of secreting two classical neurotransmitters from the same neuron is still largely unidentified. In this thesis, we investigated how different cholinergic nuclei modulate behavioural functions. To …

Neural Substrates Of Reward, Error, And Effort Processing Underlying Adaptive Motor Behaviour, Dimitrios J. Palidis

Electronic Thesis and Dissertation Repository

Human motor control is highly adaptive to new tasks and changing environments. Motor adaptation relies on multiple dissociable processes that function to increase attainment of reward and to reduce sensory error and physical effort as costs. This thesis tests the hypothesis that fronto-striatal and dopaminergic neural systems contribute to specific aspects of motor adaptation that occur through reinforcement of rewarding actions.

Behavioral tasks were designed to isolate learning in response to feedback conveying information about reward, error, and physical effort. We also measured behavioral effects of savings and anterograde interference, by which memories from previous motor learning can facilitate or …

Dissecting The Neural Circuits Mediating Pain-Induced Negative Affect And Drug-Seeking Behaviors, Tamara Markovic

Arts & Sciences Electronic Theses and Dissertations

Understating the function of neural circuits and the state-depended adaptations within them is one of the fundamental aims in the field of neuroscience. With recent technical developments in monitoring circuit dynamic, such as calcium (Ca2+) imaging, visualizing synaptic connections using viral approaches and manipulating neuronal activity in cell-specific manner such as optogenetic and chemogenetics, we are now able to mechanistically link the activity and function of neural circuits with behavioral outcomes.Using the above-mentioned techniques, I demonstrate that pain induces somatic adaptations in the Ventral Tegmental Area (VTA) dopamine (DA) neurons to drive anhedonia-like behaviors. Pain is a complex phenomenon composed …

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 …

Muscarinic Excitation Of Dopamine Neurons In The Ventral Tegmental Area Via Activation Of A Trpc-Like Cation Conductance, Yu Tzu Chen

Theses and Dissertations

Dopaminergic (DA) neurons in the ventral tegmental area (VTA) play a crucial role in reward and motivational behaviors, including the development of drug addictions. VTA DA neurons receive excitatory cholinergic inputs from the mesopontine tegmentum. Blockage of the M5 muscarinic receptor in DA neurons has been shown to attenuate drug-induced DA release and abuse-related behaviors, but the molecular mechanism is unknown. In this study, experiments were designed to identify the electrophysiological effects of muscarinic agonism in the modulation of action potential kinetics and firing patterns in VTA DA neurons of mice. Pharmacology of the muscarinic receptor-evoked current was also characterized. …

The Effects Of 17alpha-Hydroxyprogesterone Caproate On The Development Of The Mesocortical Dopamine Pathway And Cognitive Behavior, Melanie Lolier

Legacy Theses & Dissertations (2009 - 2024)

This dissertation examined the complex developmental impact of the clinically relevant synthetic progestin 17α-hydroxyprogesterone caproate (17-OHPC) on medial prefrontal cortex (mPFC) development. In rodents, the effects of 17-OHPC are subtle, but significant. In the Chapter II, we observed that 17-OHPC abolishes sex differences in dopaminergic fiber innervation and alters microglia phenotype in the prelimbic and infralimbic areas by the end of the first postnatal week. In the third chapter, the overall effect of 17-OHPC on the ontogeny of dopaminergic fiber innervation and synaptic bouton density were used to characterize the timing and duration of treatment effects in the mPFC. In …

Behavioral, Endocrine, And Neural Responses To Stress In Postpartum And Nulliparous Rats : Potential Mechanisms Of Postpartum Stress Resilience, Joanna Medina

Legacy Theses & Dissertations (2009 - 2024)

Major depressive disorder is one of the most pervasive psychiatric illnesses in the United States. Women are at greater risk for developing depression, particularly during their childbearing years. Approximately 17% of new mothers develop postpartum depression within 4 weeks after parturition. The risk for postpartum depression is even greater in women who do not breastfeed or stop breastfeeding early. Major depressive disorder and postpartum depression share the same symptomology and common etiological bases. Dysregulated stress responses, dopamine activity, and neuroinflammation are recognized mechanisms for depression. The transition to motherhood encompasses physiological and behavioral adaptations in the brain essential for ensuring …

Tonic And Phasic Amperometric Monitoring Of Dopamine Using Microelectrode Arrays In Rat Striatum, Martin Lundblad, David A. Price, Jason J. Burmeister, Jorge E. Quintero, Peter Huettl, Francois Pomerleau, Nancy R. Zahniser, Greg A. Gerhardt

Neuroscience Faculty Publications

Here we report a novel microelectrode array recording approach to measure tonic (resting) and phasic release of dopamine (DA) in DA-rich areas such as the rat striatum and nucleus accumbens. The resulting method is tested in intact central nervous system (CNS) and in animals with extensive loss of the DA pathway using the neurotoxin, 6-hydroxyDA (6-OHDA). The self-referencing amperometric recording method employs Nafion-coated with and without m-phenylenediamine recording sites that through real-time subtraction allow for simultaneous measures of tonic DA levels and transient changes due to depolarization and amphetamine-induced release. The recording method achieves low-level measures of both tonic and …