Neuroscience and Neurobiology Commons^™

Competitive And Noncompetitive Credit Assignment To Reward Cues In The Lateral Orbitofrontal Cortex, Mihwa Kang

Dissertations, Theses, and Capstone Projects

This dissertation investigates the mechanisms underlying variations in credit assignment to reward cues, with a focus on the lateral orbitofrontal cortex (lOFC). The lOFC has long been implicated in signaling reward expectancies, with controversy as to whether it signals the economic value of future outcomes, their sensory features to guide behavior or both. However, whether the lOFC signals the relative (competition-dependent) or absolute (contiguity-dependent) credit of cues is unknown. To address this, I employed a combination of novel behavioral assays, in-vivo electrophysiological recordings and optogenetic stimulation in rats. In Chapter 2, I tested the suitability of a self-initiating variant of …

Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra

Markey Cancer Center Faculty Publications

Opioid use disorder is a major public health crisis that is manifested by persistent drug-seeking behavior and high relapse frequency. Most of the available treatments rely on targeting opioid receptors using small molecules that do not provide sustained symptom alleviation. Psychoplastogens are a novel class of non-opioid drugs that produce rapid and sustained effects on neuronal plasticity, intended to produce therapeutic benefits. Ibogalogs are synthetic derivatives of iboga alkaloids that lack hallucinogenic or adverse side effects. In the current study, we examine the therapeutic potential of DM506, a novel ibogalog lacking any cardiotoxic or hallucinogenic effects, in cue-induced seeking behavior …

Large Deviation Theory In Stochastic Processes: Applications To Biological Modeling, Moshe C. Silverstein

Dissertations

This dissertation delves into developing and applying stochastic models to analyze complex biological systems. It leverages Large Deviation Theory (LDT) to gain insights into these systems, focusing on two key examples: neural networks and calcium signaling dynamics. Traditional deterministic methods frequently fail to capture biological processes' randomness and inherent variability. Meanwhile, many stochastic approaches struggle to be mathematically tractable or provide accessible insights. The approach introduced in this study provides rigorous mathematical frameworks to enhance understanding of these stochastic behaviors while remaining tractable and insightful.

A stochastic model for a random biological neural network is constructed that addresses the dependencies …

The Neuroscience Of Mindfulness Based Art Therapy: A Literature Review, Elizabeth Strasser

Expressive Therapies Capstone Theses

Art therapy and neuroscience are two fields which are currently growing and expanding with the development of new technology which allows for therapists and scientists to advance their understanding of how the brain and the body respond to the world around us. The interaction between the brain, body, and environment is complex, and for the sake of clarity for this thesis this interaction will be conceptualized through the lens of the body-mind model, polyvagal theory, neuroaesthetics, the flow state, mindfulness, sensory engagement, and art as therapy. Neuroscience in relation to psychology can be used to develop a deeper understanding of …

Unraveling The Role Of Hid-1: Insights Into Sgii Regulation, Breanna L. Sellers

Electronic Theses and Dissertations

The regulated secretory pathway is important for the secretion of hormones and neuropeptides from large dense core vesicles (LDCVs). Dysregulation of the biogenesis of LDCVs can result in metabolic and neurological diseases. Recent studies have suggested that the peripheral membrane protein HID-1 plays a role in the sorting and storage of granins which contribute to LDCV biogenesis. To further understand how HID-1 influences the regulation of granins, we investigated potential HID-1 interactors. We determined that while HID-1 is likely functioning in the same pathway as USP25, a deubiquitinating enzyme (DUB), the cause of reduced cellular SgII levels is likely not …

Slow Ramping Emerges From Spontaneous Fluctuations In Spiking Neural Networks, Jake Gavenas, Ueli Rutishauer, Aaron Schurger, Uri Maoz

Psychology Faculty Articles and Research

The capacity to initiate actions endogenously is critical for goal-directed behavior. Spontaneous voluntary actions are typically preceded by slow-ramping activity in medial frontal cortex that begins around two seconds before movement, which may reflect spontaneous fluctuations that influence action timing. However, the mechanisms by which these slow ramping signals emerge from single-neuron and network dynamics remain poorly understood. Here, we developed a spiking neural-network model that produces spontaneous slow ramping activity in single neurons and population activity with onsets ~2 s before threshold crossings. A key prediction of our model is that neurons that ramp together have correlated firing patterns …

Multiple Guidance Mechanisms Control Axon Growth To Generate Precise T-Shaped Bifurcation During Dorsal Funiculus Development In The Spinal Cord, Bridget M. Curran, Kelsey R. Nickerson, Andrea R. Yung, Lisa V. Goodrich, Alexander Jaworski, Marc Tessier-Lavigne, Le Ma

Farber Institute for Neuroscience Faculty Papers

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis …

Long-Term Neurodevelopmental Outcomes Post-Chronic Midazolam Exposure During Early Life, Nghi M. Nguyen

Theses & Dissertations

In recent decades, the rising number of neonates born in the Neonatal Intensive Care Unit (NICU) due to prematurity has raised concerns about their overall well-being and development. Premature neonates are at higher risk of health complications and often require invasive procedures. These invasive procedures often induce stress and agitation, prompting physicians and healthcare providers to provide sedation or general anesthesia to manage discomfort. Epidemiological studies of human patients have revealed a correlation between childhood exposure to general anesthetic and sedative agents and subsequent cognitive deficits. This association is also supported in animal models, which shows that exposure to anesthetics …

The Effect Of Acute Social Isolation On Neural Molecular Responses In Components Of The Social Decision-Making Network, Patricia C. Lopes, Madeleine Chang, Faith Holloway, Biola Fatusin, Sachin Patel, Chandler Siemonsma, Morgan Kindel

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Prolonged or chronic social isolation has pronounced effects on animals, ranging from altered stress responses, increased anxiety and aggressive behaviour, and even increased mortality. The effects of shorter periods of isolation are much less well researched; however, short periods of isolation are used routinely for testing animal behaviour and physiology. Here, we studied how a 3 h period of isolation from a cagemate affected neural gene expression in three brain regions that contain important components of the social decision-making network, the hypothalamus, the nucleus taeniae of the amygdala, and the bed nucleus of the stria terminalis, using a gregarious bird …

Prelimbic Neuronal Ensembles In Natural Reward Seeking, Roger Ian Grant

MUSC Theses and Dissertations

External cues can become powerful motivators of behavior when paired with rewarding stimuli, such as natural rewards or drugs of abuse, as is the case in individuals with substance use disorder (SUD). The dorsomedial prefrontal cortex (dmPFC) has been implicated as a neural substrate which encodes cue-reward associations and has been shown to exert top-down control over both natural and drug reward seeking. We and others have shown that activity within the dmPFC is heterogeneous during reward seeking, with some neurons displaying excitatory responses to reward-predictive cues, and others showing inhibitory responses to the same cues. Furthermore, this response heterogeneity …

Investigating The Role Of Insulin-Like Signaling In Paclitaxel-Induced Nociceptive Hypersensitivity Using Drosophila Melanogaster, Sreepradha Sridharan

Dissertations and Theses (Open Access)

Paclitaxel (PTX), a chemotherapeutic that alters microtubule dynamics, is known to induce nociceptive hypersensitivity and sensory neuron damage in human patients and in Drosophila larvae. We used a modified feeding protocol to establish a genetically tractable Drosophila model of PTX-induced hypersensitivity. Larvae fed PTX exhibited hypersensitivity to thermal and mechanical stimuli. Thermal hypersensitivity was observed at low concentrations of PTX (even below 1 μM per ml of food), begins within 8 hours of PTX feeding, and did not completely resolve at the larval stage. Live imaging of peripheral thermal nociceptors showed that this hypersensitivity precedes observable neuronal damage. At low …

The Role Of The Circadian Clock In The Paraventricular Nucleus Of The Hypothalamus In Diurnal Energy Balance, Rachel Van Drunen

Dissertations and Theses (Open Access)

Circadian rhythms are internal biological rhythms that drive oscillations in physiology and metabolism. Maintained at the level of individual cells throughout the body, the circadian clock is necessary for driving tissue-specific temporal programs of energy balance. Though loss of the circadian transcription factor, BMAL1, in the paraventricular nucleus (PVN) of the hypothalamus has revealed its importance in driving rhythms in energy intake and metabolism, its transcriptional functions across time and in individual cell types in the PVN are not well understood. In this study, we show that loss of BMAL1 in the PVN not only results in arrhythmicity in processes …

Decision-Making In Rats: Effects Of Drug Abuse, Safa Binte Hossain

Open Access Theses & Dissertations

Decision-making is a critical cognitive function, often impaired by substance abuse. Understanding the underlying mechanisms in both human and animal models is essential for developing effective treatments. This thesis aims to study approach-avoid decision-making in rats and focuses on the impacts of oxycodone self-administration and alcohol abuse on approach-avoid decision-making.We hypothesize that oxycodone self-administration will alter decision-making in female rats, revealing sex differences and distinct psychometric functions, alcohol habituation will similarly affect decision-making in male rats. The study involved 23 Long Evans rats (11 males and 12 females) for decision-making behavioral study connecting multiple levels of rewards and costs combinations. …

Cerebrovascular Reactivity Mri As A Biomarker For Cerebral Small Vessel Disease–Related Cognitive Decline: Multi-Site Validation In The Markvcid Consortium, Peiying Liu, Zixuan Lin, Kaisha Hazel, George Pottanat, Cuimei Xu, Dengrong Jiang, Jay J. Pillai, Emma Lucke, Christopher E. Bauer, Brian T. Gold, Steven M. Greenburg, Karl G. Helmer, Kay Jann, Gregory Jicha, Joel Kramer, Pauline Maillard, Rachel M. Mulavelil, Pavel Rodriguez, Claudia L. Satizabal, Kristin Schwab, Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J. J. Wang, Rita R. Kalyani, Abhay Moghekar, Paul B. Rosenberg, Sevil Yasar, Marilyn Albert, Hanzhang Lu

Neurology Faculty Publications

INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.

METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.

RESULTS: CVR …

High Fat Diet & Social Isolation: Interactive Effects On Pain, Cognition, & Neuroinflammation, Ian M. Campuzano

Research Psychology Theses

Prior research has established a role for both social isolation and exposure to high fat Western diets in altering a range of behaviors from reduced memory performance to increased depression-like behaviors. The present study scrutinizes the interplay among these variables during the peri-adolescent developmental phase, utilizing Long-Evans rats as the experimental model. Our overarching hypothesis is that rats exposed to either social isolation, a high-fat diet, or both will result in heightened pain sensitivity, diminished cognitive flexibility, and increased neuroinflammatory responses within brain regions implicated in sociability, cognition, memory, and pain processing. Behavioral flexibility will be assessed using a maze-based …

Transcriptomics Analysis Reveals Potential Regulatory Role Of Nsmase2 (Smpd3) In Nervous System Development And Function Of Middle-Aged Mouse Brains, Zhihui Zhu, Timothy S. Mcclintock, Erhard Bieberich

Markey Cancer Center Faculty Publications

Neutral sphingomyelinase-2 (nSMase2), gene name sphingomyelin phosphodiesterase-3 (Smpd3), is a key regulatory enzyme responsible for generating the sphingolipid cer- amide. The function of nSMase2 in the brain is still controversial. To better under- stand the functional roles of nSMase2 in the aging mouse brain, we applied RNA-seq analysis, which identified a total of 1462 differentially abundant mRNAs between +/fro and fro/fro, of which 891 were increased and 571 were decreased in nSMase2-deficient mouse brains. The most strongly enriched GO and KEGG annota- tion terms among transcripts increased in fro/fro mice included synaptogenesis, syn- apse development, synaptic signaling, axon development, and …

Emotional Content In Working Memory Processes: An Fmri Study., Manal Zafar

Electronic Theses and Dissertations

Working memory (WM) is a dynamic system that processes and manipulates both goal-relevant and goal-irrelevant information, integral to higher-level cognition and executive control (Fujii, 2001; Nyberg & Erikkson, 2016). The processing and manipulation of representations is modulated by the affective nature of the information (Pessoa, 2009) such that negative information can either impair or enhance WM processing. WM impairments are seen commonly across clinical disorders such as depression, anxiety, PTSD and schizophrenia (Levens & Gotlib, 2010; Joorman et a., 2011; Brodziak et al., 2015). Specifically, negative information is known to have differential processing in WM compared to neutral and positive …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Establishing A Mouse Model Of Cerebral/Cortical Visual Impairment., Dana K. Oakes

Electronic Theses and Dissertations

Cerebral/cortical visual impairment (CVI) is a disorder most often caused by perinatal hypoxic injury to the developing brain. CVI is the leading cause of childhood visual impairment in developed nations, encompassing deficits in many aspects of vision including visual acuity, contrast sensitivity, and object recognition. The pathophysiology of CVI is not well understood because no animal model currently exists to study this disorder. Because there is no animal model, the pathophysiology of CVI is poorly understood. Here, we developed a murine early postnatal hypoxic model of CVI by exposing mice to 9.5% O₂ at postnatal day (P)3 for a …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

The Role Of The Circadian Clock In Disease And Tissue Function, Marvin Wirianto

Dissertations and Theses (Open Access)

The mammalian circadian clock responds to the 24-hour daily cycle and regulates tissue-specific gene expression and downstream physiology. The central pacemaker located in the hypothalamic suprachiasmatic nuclei (SCN) synchronizes the peripheral clocks in different tissues. This dissertation aims to uncover specific circadian regulatory mechanisms in the brain and skeletal muscle.

Alzheimer’s Disease (AD) is the most common type of dementia. It has previously been shown that there is a strong correlation of disease progression with circadian rhythm decline. We showed that circadian modulation by a small molecule Nobiletin (NOB) was able to mitigate AD pathogenesis. Furthermore, NOB significantly alleviated the …

Wired For Success: A Neurobiological Approach To Improving The Academic Outcomes Of Middle School Boys, Allison Emery

University Honors Theses

Male accomplishment in scholastic settings has been declining globally for the last decade, leading to long-term consequences for boys and men. Possible neurobiological underpinnings of the gender gap in education are discussed in this literature review. While male and female differences have, in the past, largely been considered socialized, recent science also confirms neurobiological variances between male and female development. These distinctions are assessed for their potential ties to the decline in male academic success, and are correlated to classroom practices, strategies and interventions meant to increase boys' engagement and performance.

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

Poly (Adp-Ribose) Polymerase-1 (Parp1) Expression In The Frontal Cortex And Hippocampus In Major Depressive Disorder (Mdd) And Suicide, Ramona Faith Fulkerson

Electronic Theses and Dissertations

Major Depressive Disorder (MDD) is a prevalent psychiatric disorder that has a complex pathophysiology. In this study we evaluate the expression of PARP1 and the downstream alarmin protein high mobility group box 1 (HMGB1) in two brain areas that have demonstrated pathology in MDD. MDD donors were compared to controls. MDD subgroups that died by suicide were also compared to those that did not die by suicide. Immunoblotting to determine PARP1 and HMGB1 protein expression was performed in white and grey matter from the frontal cortex and the hippocampus. In BA10 white and grey matter, PARP1 protein expression was significantly …

Gpr171 Modulates Mood, Consummatory Behaviors, And Morphine Antinociception In A Sexually Dimorphic Pattern In Mice, Megan C. Raddatz

All Graduate Theses and Dissertations, Fall 2023 to Present

Receptors in the brain influence everything from complex behaviors related to mood, all the way to simple physiological functions like the way a person moves. Receptors are activated or inactivated by chemicals or hormones that the body produces or that are created to mimic the body’s natural chemicals. Of the hundreds of receptors in the brain, GPR171 is particularly interesting because new drugs have been created to activate or block the receptor, and are being proposed for the treatment of different disorders, particularly disorders related to pain. GPR171 has been shown to affect pain behaviors, eating, and mood-related behaviors, but …

Advancing Methods For Studying The Neuroscience Of Sex Variability And Diversity, Vic Shao-Chih Chiang

Graduate Doctoral Dissertations

Sex variability and diversity are pervasive across taxa and genera. Society is heavily structured around sex/gender conceptualizations, and neuroscience research actively shapes these constructs. This dissertation adopts frameworks that challenge ideologies perpetuating sex/gender injustices and developed neuroscience-related methodologies that could advance the conceptualisations of sex. First, I studied B6D2F1 mice which exhibit sexual behaviour months after castration. This challenged the dogma that sexual behaviour is dependent on gonadal steroid hormones. I enhanced the behavioural analysis of these mice using deep learning techniques. Second, applying similar deep learning methods, I refined the behavioural analysis of Astatotilapia burtoni cichlids, which exhibit sexual …

The Effects Of Non-Invasive Brain Stimulation On Excitability Of The Primary Motor Cortices And Complex Motor Task Learning, Erik Woodruff Wilkins

UNLV Theses, Dissertations, Professional Papers, and Capstones

Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are promising non-invasive brain stimulation techniques, particularly for clinical applications involving altered or impaired motor function, such as in stroke and Parkinson’s disease. Although tDCS and tACS are different modalities, both forms of stimulation operate on the same principle - weak electrical currents are delivered through electrodes placed on the scalp in specific configurations known as “montages”. The most commonly used montage for targeting the primary motor cortex (M1) is the M1-SO configuration. This montage leverages the established observation that cortical regions directly beneath the anode generally increase in …

Evaluating The Effects Of Concussions And Tdcs On Executive Functioning In College Students, Macey Hoffman, Erin Dychdala

Neuroscience Summer Fellows

This PowerPoint presentation evaluates the effects of concussions and tDCS treatment on executive functioning in students at Ursinus College.

Host-Microbiome Interactions In The Teleost Brain, Amir Mani Varnoosfaderani

Biology ETDs

This dissertation investigates host-microbial interactions within the teleost brain, previously considered sterile. Reviewing current literature highlights significant gaps in understanding teleost brain immunity, despite prevalent neurotropic diseases. We mapped the immune profiles of rainbow trout brains and meninges, revealing the olfactory bulbs as the immune effector part of the brain and the optic tectum as a nod2 expression hub. High il6 and il10 levels were noted in the telencephalon. A persistent bacterial community within healthy salmonid brains shares diversity with gut and blood microbiota. Brain bacterial isolates exhibit genomic signatures for brain colonization and polyamine biosynthesis. The microbiota shifts across …

Energy Drinks, Shots, And Pre-Workout Supplements: A Brief Review, Jason M. Curtis, Jose Antonio

Journal for Sports Neuroscience

Abstract

Introduction: There are many purported benefits, both physically and mentally, to consuming energy drinks, energy shots, and multi-ingredient pre-workout supplements ¹.

Methods: This current review, we used studies that investigated the benefits of ED, ES, and MIPS products. We looked for studies that reported the effects of these products, both physical and/or mental.

Review Findings: Current literature on these products suggests that the consumption of these ergogenic aids may increase power, force production, anaerobic production, muscular endurance, and endurance performance in athletes as well as improvement in many indices of mental performance ^2,15.

Practical …