Investigating Undergraduate Conditioned Place Preference Utilizing Virtual Alcohol Stimuli, Nikole A. Rodriguez Torres, Robert Astur, Jeffrey Divino

Honors Scholar Theses

Alcohol use remains a major concern among college students, with binge drinking linked to serious physical and mental health problems. But how much does the environment influence these addictive behaviors? The relationship between environmental cues and alcohol related behaviors is a critical area of study, particularly understanding reward and motivation mechanisms. Binge drinking, common among college students, is associated with a range of negative outcomes such as physical harm, legal issues, poorer overall health, sleep problems, depression, anxiety, and severe thoughts of suicide. In our study, college undergraduates were exposed to two VR rooms: one with alcohol-related stimuli and one …

Neurodevelopmental And Environmental Mechanisms Of Invasion, Proliferation, And Tumor Cell Fate Specification In Glioblastoma, Bianca Lynn Myers

Biomedical Sciences ETDs

Glioblastomas (GBMs) are the most aggressive primary brain tumors, and despite over 50 years of research efforts, the median survival remains at 14 months post-diagnosis. The current standard of care consists of maximal surgical resection radiotherapy with concurrent chemotherapy using temozolomide. However, the highly proliferative and invasive nature of GBM cells renders total resection nearly impossible as tumor cells invade the surrounding healthy tissue. The molecular and environmental drivers of these tumorigenic phenotypes are largely unknown. Here, we demonstrate that the neurodevelopmental transcription factor ASCL1 enhances tumor cell proliferation and invasion while activating the expression of a neural stem cell …

Apolipoprotein E4, Tauopathy, And Brain Injury: Molecular Insights Into Alzheimer's Disease Pathology, Nashanthea J. Roland

Theses & Dissertations

Alzheimer’s disease (AD) is the world’s leading cause of dementia, characterized by progressive atrophy of the hippocampal and cortical brain regions, synapse damage and loss, and a buildup of senile plaques and neurofibrillary tangles composed of β-amyloid peptides and hyperphosphorylated tau, respectively. While age is the most significant risk factor for developing AD, apolipoprotein E4 (APOE4) is the strongest genetic risk factor for AD. Although it is known that APOE4 influences tau pathology, the molecular mechanisms by which APOE4 drives AD pathogenesis and progression remain unclear. In addition to intrinsic contributions to AD, there are many extrinsic factors that can …

Claiming More To Cope: Does Ostracism Increase Overclaiming?, Katy Q. Chen

Honors Theses

In a pre-registered online study, we investigated the relationship between ostracism and overclaiming. Ostracism is the act of deliberately or unintentionally excluding and ignoring others. Overclaiming refers to the behavior of exaggerating one’s knowledge or familiarity with specific topics, often as a way of attempting to present oneself as more knowledgeable or competent than one actually is. Drawing from the temporal need-threat model, we hypothesized that ostracized individuals, as a compensatory response, would likely overclaim more compared to included individuals. This online study simulated a work experience where participants were asked to answer questions about their work-related experiences and opinions. …

The Endocannabinoid System's Influence And Modulation Of Nociception, Doreen M. Flannery

Honors Thesis

The anatomy and physiology of pain is a well-defined pathway where noxious stimuli is processed by different systems in the brain. The central research question of this review is how can we better understand the neurobiological effects pain has, and assess if there is therapeutic potential in using endocannabinoids to modulate these effects. Endocannabinoids are signaling molecules that play a key role at both the cellular and molecular level in modulating both acute and chronic pain by influencing different processes within each level that affect how the body responds to both internal and external stimuli. The endocannabinoid system is a …

Neurodegenerative Disease Mechanisms: Mitochondrial Impairment, Tau Aggregation, And Neuroinflammation As Central Drivers Of Disease Progression, Luis D. Estrella

Theses & Dissertations

The study of the intricate molecular mechanisms behind the pathology of neurodegenerative diseases has become a primary research area in the past decades. The major branches of these studies involve both disease progression and disease pathogenesis, in which neuroscientists have studied, and continue to study, the role that mitochondrial dysfunction, aberrant protein aggregation (like Tau), and immune cell reactions have on these. However, more recent studies have shined light to the fact that these three pathological features are not independent from one another and that their synchronous contributions may be the ultimate driver of neurodegeneration. This dissertation encompasses four different …

The Role Of Presynaptic Proteins In Alcohol Sensitivity And Tolerance, Madhumitha Gundluru

Honors Theses

Mammalian Unc13 (Munc13) and Drosophila Unc13 (Dunc13) are presynaptic active zone proteins essential for synaptic vesicle docking and priming in a neuron. Alcohol binds to the C1 domain of Munc13, which inhibits DAG binding. The reduction in DAG binding by Munc13 decreases the probability of vesicle fusion with the membrane, decreasing neurotransmitter release. Heterozygotes for a Dunc13 loss-of-function allele are behaviorally resistant to alcohol, physiologically resistant to alcohol, molecularly resistant to alcohol, and self-administer significantly more alcohol than control flies. Therefore, genetically reducing Dunc13 mimics a state of alcohol tolerance in the fly. The two main Dunc13 isoforms, Dunc13A and …

Impaired Dnajb2 Response To Heat Shock In Fibroblasts From A Neuropathy Patient With Dnajb2/Hsj1 Mutation: Cystamine As A Potential Therapeutic Intervention, Raj K. Pradhan, Nikolas G. Kinney, Brigid K. Jensen, Hristelina Ilieva

Farber Institute for Neuroscience Faculty Papers

Background and Objectives: Neuropathy is a debilitating disorder characterized by peripheral nerve dysfunction and damage to sensory, motor, and autonomic neurons and their axons. While homozygous mutations in DNAJB2/HSJ1 have been linked to early-onset neuropathy, a heterozygous DNAJB2 c.823+6C>T was discovered in an adult patient with severe sensory–motor polyneuropathy. This mutation is predicted to affect both isoforms of the protein. DNAJB2 (HSP40), a key member of the heat shock protein family, plays a critical role in cellular protection and stress, including response to heat shock. DNAJB2 traffics unfolded proteins to another heat shock protein, HSP70, and activates its ATPase …

Behavioral And Neural Microstructures Of Dynamic Cue-Motivated Responses, Erica Townsend

Dartmouth College Ph.D Dissertations

Sign-tracking, a conditioned response in which animals are physically attracted to reward-predictive cues due to motivational value attribution, is known to be persistent but can be flexible under some circumstances. For example, during an omission paradigm, in which vigorous responses must be withheld to avoid reward cancellation, animals can quickly restructure their responses. However, sign-tracking does not cease entirely, and cue attraction persists. This dissertation explores the behavioral and neural mechanisms underlying the simultaneous persistence and flexibility of sign-tracking during omission procedures. First, a novel method for behavioral analysis is introduced to accurately depict sign-tracking animals in dynamic tasks such …

Biomarkers That Could Explain Parasite-Induced Behavioral Alterations In The Golden Shiner (Notemigonus Crysoleucas) – Posthodiplostomum System, Laura D. Nicolas

All HCAS Student Capstones, Theses, and Dissertations

Trophically transmitted parasites require an intermediate host to be consumed and often manipulate host phenotype (i.e., morphology, physiology, and/or behavior) to increase predation risk by definitive hosts. Posthodiplostomum is a trematode with a complex life cycle involving snails as first hosts, fish as second intermediate hosts, and piscivorous birds as definitive hosts. In fish hosts, Posthodiplostomum infection has been linked to increased predation, suggesting suppression of antipredator behaviors. However, the specific physiological pathways remained unexplored and changes in the host’s neural, endocrine, and immune systems could be involved. Thus, I examined whether Posthodiplostomum infection intensity was associated with brain serotonin …

Mitochondrial Network Expansion And Loss During Oligodendrocyte Life And Death, Xhoela Bame

Dartmouth College Ph.D Dissertations

Oligodendrocytes are the myelinating cells of the central nervous system, known for modulating signal transmission, refining neural circuits, and providing metabolic support to axons. Oligodendrocytes are generated throughout life from oligodendrocyte precursor cells (OPCs) and are damaged or lost in demyelinating and neurodegenerative diseases and age-related pathologies. Thus, understanding the cellular checkpoints that occur during the generation and degeneration of oligodendrocytes is crucial for maintaining their population in health and recovering it in disease and aging.

Using high-resolution optical imaging, I have discovered a dynamic redistribution and subcellular partitioning of mitochondria during oligodendrogenesis. Mitochondria transiently expanded towards the differentiating OPC …

The Impact Of Insufficient Sleep On The Serial Reproduction Of Information, David L. Dickinson, Sean P. A. Drummond

ESI Publications

Story retelling is an important form of communication, cultural practice, and message transmission. Insufficient sleep is known to affect relevant cognitive skill areas necessary for story retelling or transmission fidelity. We conducted a preregistered randomized cross-over study on n = 155 young adults with exogenously assigned nightly sleep levels experienced in their at-home environments. A serial story reproduction task was administered online, and chains of up to three retells of a given story involved varied numbers of sleep restricted (SR) versus well-rested (WR) retellers. While story content decayed with each retell, group-level analysis showed that additional SR retellers in a …

Developing A Trial Unique Sequencing Task For Mice, Yader Gomez, Lilly Hagos, Gage Pompa, Ariana Mitic, Orlando Montiel, Talha Soluoku

Undergraduate Research Symposium Posters

The hippocampus and the anterior cingulate cortex (ACC) play distinct yet complimentary roles in the performance of cognitively demanding tasks.

While rodent models cannot truly capture human cognition, there is a serious need to develop more cognitively demanding rodent tasks to better understand human cognition to develop new tools to fight neurodegeneration.

Sequencing tasks are some of the most difficult for rodents to perform and are notoriously difficult to train.

Cutting edge interactive touch screen technology allows us to test an endless array of sequences, in a sound-controlled enclosure featuring a simple behavioral response for the mice.

Study Aim: To …

Know Thyself: A History Of Ancient Neuroscience, Alex Delano

Departmental Honors & Graduate Capstone Projects

Neuroscience is often described as one of the youngest bodies of science, but documented study of the brain begins as early as the Neolithic period. The ancient Mediterranean was a hub for science, mathematics, philosophy, and literature, all disciplines necessary for the study of the brain. Evidence of neurosurgical procedures like trepanation and craniotomy began in the Neolithic period and were practiced and improved upon throughout the ancient Mediterranean. The first detailed studies on brain anatomy were carried out in the 3^rd century BCE in Greece which created a necessary structure for future scientists to build on. While many …

Characterizing The Medial Forebrain Bundle In Adolescents With Anhedonic Depression, Tina Nguyen

Biological Sciences Undergraduate Honors Theses

Adolescent depression has quickly grown in prevalence, yet the underlying neuropathology remains poorly understood. Anhedonia–the diminished ability to experience pleasure–is a core symptom of melancholic depression. Early identification of biomarkers associated with anhedonic depression could help mitigate the severity of the disorder by enhancing treatment efficacy. Blunted functionality of the nucleus accumbens (NAcc), the reward center of the brain, and abnormal dopaminergic activity in the ventral tegmental area (VTA) have both been linked to depression. Furthermore, glutamatergic input from the hypothalamus modulates the VTA which in turn, downregulates dopamine release in the NAcc. However, there is limited evidence supporting that …

Effects Of Novel Dopamine D4 Receptor-Targeted Compounds On Locomotor Activity And Anxiety-Like Behavior In Male And Female Sprague Dawley Rats, Samantha Alyse Walkow, Noah A. Ivak, Daniel Chandler, John Tkaczynski, Thomas M. Keck, Comfort A. Boateng, Eleni Papadopoulos, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

The consequences of modulating subtypes of G protein coupled dopamine receptors are broadly studied for their role in decision making behavior, specifically in situations involving uncertain risk and reward. The actions of dopamine D4 receptors (D4Rs) on these complex processes are the least understood, particularly due to a lack of available compounds with suitable selectivity for D4Rs. Further, current research often fails to evaluate how modulating specific dopamine receptor subtypes may affect locomotor activity and anxiety-like behavior as confounding factors prior to assessing their function in behavioral assays of higher order decision making. The goal of the current study was …

Mechanisms Of Behavioral Change In Hosts Of Toxoplasma Gondii: A Review, Olivia Grimsley

Senior Honors Theses

The parasite Toxoplasma gondii is a highly ubiquitous parasite that latently infects an estimated 33% percent of the global population. Toxoplasmosis is of obvious clinical significance due to the extremely high risks to the unborn who contract it congenitally. Less attention has been given to a more subtle aspect of latent infection, which is the behavioral alterations that are commonly experienced by those who contract the parasite. Infected individuals commonly display a variety of altered behaviors, such as increased aggression and risk-seeking behaviors, depression, higher tendency towards suicide and self-directed violence, a loss of fear response, and a greatly increased …

Poor Sleep Quality Is Associated With Decreased Structural Coherence Of Mesolimbic Dopamine Projections In Children, William A. Walker

Psychological Science Undergraduate Honors Theses

Insomnia is the second most common mental disorder that affects approximately 10% of the population. An additional one-third of the population experiences occasional symptoms of insomnia like difficulty falling asleep or staying asleep. Sleep quality is also a key indicator of overall mental and physical health; however, researchers have only begun to study the effects of the structure of the mesolimbic pathway on sleep cycle regulation and quality. Emerging research suggests that mesolimbic dopamine projections from the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAcc) play a role in sleep-wake regulation. In this study, I analyzed data from the …

Involvement Of The Mpfc In Narcissism And Celebrity: A Transcranial Magnetic Stimulation Study, Sydney Ash

Theses, Dissertations and Culminating Projects

Narcissism is typically characterized by extreme self-focus, lack of empathy for others, and emotional regulation deficits. Grandiose narcissism has been linked to an increased desire for fame, while vulnerable narcissism has been linked to an increase in celebrity worship. While there is a lack of research concerning the neural correlates of desire for fame and celebrity worship, narcissism has been correlated with the medial prefrontal cortex (mPFC) in various studies. The current study aimed to identify relationships between grandiose and vulnerable narcissism, fame appeal, celebrity attitudes, need to belong, and self-esteem using six scales. We also targeted the mPFC with …

Dabigatran Reduced Acute Microgliosis In A Mouse Model With Tbi, Nicholas R. Eltman, Rashmeena Abbasi, Mary C. Kosciuk, Syed Ahmed, Jose L. Pascual, Randel L. Swanson, Nimish K. Acharya

Rowan-Virtua Research Day

Objective:

The study objective was to investigate the acute anti-inflammatory effects of dabigatran in a preclinical mouse controlled cortical impact (CCI) model of severe traumatic brain injury (TBI).

Design

Mice were separated into three groups: controlled cortical impact (CCI) with dabigatran (drug treatment, n=5), CCI with saline (positive control, n=5), and sham CCI without saline or dabigatran (negative control, n=3). Dabigatran (80mg/kg) or saline was administered orally at 2, 10, 18, 26, 34, and 42 hours following experimental CCI in the drug treatment or positive control groups, respectively. Animals in the negative control group received sham CCI only. 48h following …