Systems Neuroscience Commons^™

Towards Identifying Fear And Safety Network States Across Sex, Rhonda Kolaric

Dissertations, Theses, and Capstone Projects

Post-traumatic stress disorder (PTSD) is a trauma- and stressor-related disorder with a lifetime prevalence of 5-6% in men, and 10-12% in women (National Center for PTSD). Generalized anxiety disorder (GAD) is a highly prevalent anxiety- and depression-related psychiatric disorder with a lifetime prevalence of 1-2% in men, and 3-4% in women (National Institutes of Health). Both of these disorders disproportionately affect women. A hallmark feature of both disorders is the maladaptive generalization of fear, in which defensive responses extend beyond the original traumatic or threatening stimulus to neutral or unrelated cues. This overgeneralization can become debilitating, disrupting cognitive, emotional, and …

The Effects Of Chronic Nicotine Exposure On Dopamine-Mediated Reinforcement Learning And Striatal Neurotransmission, Srishti Bose

Dissertations, Theses, and Capstone Projects

Tobacco is one of the most widely used substances across the United States; tobacco consumption is linked with several diseases and is one of the leading causes of preventable death in the country. Nicotine is the active substrate found in tobacco products, acting as a stimulant, which reinforces continued use. The introduction of tobacco-free options such as e-cigarettes and oral pouches has driven an increase in nicotine exposure across the population, especially in young adults. Acute nicotine use induces neuroadaptations in the mesolimbic dopaminergic system, which mediates reinforcement learning and addiction, that potentiates reward-related neurotransmission. Furthermore, there are clinical studies …

History-Dependent Gain Control In The Paraventricular Thalamus: Neural Substrates Of Stress-Enhanced Fear Learning, Michael Martino

MUSC Theses and Dissertations

Post-traumatic stress disorder (PTSD) is characterized by hyperarousal and heightened reactivity that generalize beyond the original traumatic event, yet the neural mechanisms by which prior stress experience biases future fear learning remain poorly understood. Stress-enhanced fear learning (SEFL) is a well-validated rodent model of this phenomenon, in which a severe stressor produces persistent sensitization of subsequent fear acquisition. This dissertation used a 30-day SEFL paradigm to identify the brain-wide functional signature of stress sensitization and to identify candidate neural substrates.

Whole-brain cFos mapping during acute fear acquisition revealed a predominant pattern of suppressed neural activity in sensitized animals, with limbic …

Mapping And Modeling Threat-Evoked Brain States After Early Life Adversity, Taylor W. Uselman

Biomedical Sciences ETDs

Early life adversity (ELA) increases lifelong neuropsychiatric vulnerability. Yet how ELA reorganizes brain-wide activity and circuit coordination across later experience remains unclear. This dissertation tests the hypothesis that ELA alters adult brain-wide activity and responses to threat through disrupted coordination among neural systems that regulate emotional experience, including prefrontal-limbic and monoaminergic systems. Longitudinal manganese-enhanced MRI of adult mice exposed to standard or fragmented early care, combined with computational processing and statistical modeling, quantified brain states before, during, and long after innate predator threat. These studies established that acute threat evokes large-scale, distributed brain activity that evolves over time. ELA potentiates …

Transcranial Ac Modulation Of Cerebellar Nuclear Activity In Awake Animals, Nuran Kavakli

Dissertations

Entrainment of cerebellar nuclear (CN) cells via cerebellar transcranial alternating current stimulation (ctACS) has been reported in animals under ketamine/xylazine anesthesia. Our main objective was to demonstrate modulation of CN activity in unanesthetized, freely moving animals using ctACS. Multi-channel carbon-fiber electrodes were implanted into the interpositus nucleus for recording multi-unit (MU) activity, and thin-film electrodes were implanted subcutaneously over the posterior cerebellum for stimulation. A frequency-domain-based metric was developed to quantify modulation from MU signals. The results demonstrated modulation in a wide range of frequencies (4 Hz-300 Hz) as in anesthetized animals. In contrast, the amplitude of the peak in …

Rhythms Of Hippocampal Function And Memory After Moderate Prenatal Alcohol Exposure, Lilliana May Sanchez

Psychology ETDs

Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms of the behavioral deficits. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify …

Invisible Shipwrecks And Neurological Endangerment: The Trade-Off In Seeking Asylum - Reframing The Neurobiological Cost Of Forced Migration, Eisha Giran

CISLA Senior Integrative Projects

Forced migration along the Spain–Morocco route represents one of the most visible humanitarian crises of the twenty-first century, yet its neurological dimensions remain insufficiently examined. This paper investigates how prolonged displacement and trauma reshape neural systems involved in stress regulation, memory, and emotional processing. It introduces the concept of neurological endangerment, defined as a condition of prolonged and inescapable threat exposure during forced migration in which stress-response systems remain chronically activated, opportunities for recovery are structurally constrained, and cumulative neurobiological risk persists beyond the period of immediate danger.

To address the gap between biological measurement and lived experience, this paper …

Neural Mechanisms Underlying Jung’S Active Imagination: A Review And Hypothesis, Charles R. Fox

Journal of Conscious Evolution

Active imagination is a key technique of Jungian analysis. Despite its centrality, and its potential importance beyond Jungian psychology to the area of systems neuroscience, psychology, and consciousness studies, there are no known neurological mechanisms underlying this psychological phenomenon. There is a history of using the types of mental imagery used in active imagination to explore consciousness. The development and use of active imagination is briefly reviewed, and a case is developed that the neurology underlying active imagination would be fruitfully explored by considering it a special case of mystical experience. Active imagination primarily uses the right hemisphere processing of …

Expanding Access To Noninvasive Spinal Neuromodulation For Pediatric Spinal Cord Injury Rehabilitation: A Comparative Device Study, Alice E C Palmer

College of Arts & Sciences Senior Theses

Paralysis following spinal cord injury (SCI) has traditionally been considered permanent due to the disruption of supraspinal input to spinal motor circuits. However, growing evidence suggests that spinal networks below the level of injury retain intrinsic motor-generating capabilities through central pattern generators. Transcutaneous spinal cord stimulation (scTS) is a noninvasive neuromodulation technique that delivers electrical stimulation through the skin to reactivate these spinal networks. Although prior studies demonstrate that scTS delivered through research-grade devices is safe and effective in adults and children with chronic SCI, clinical translation remains limited by lack of FDA-approved systems, high costs, and restricted access to …

The Effects Of Sour & Spicy Food On Visual & Auditory Reflexes, Aditi Kumar, Alondra-Sophia Martinez, Magdalena E. Saad, Emma J. Welsch

Posters - 2026

• The reflex reaction time measures how quickly the nervous system can respond to a stimulus. • In the experiment, both visual and auditory reflexes were measured to evaluate differences in reaction time after the consumption of sour and spicy foods. • Spices and herbs produce different signals that interact with the nervous system. (McMullen 2024) • Comparing the response times from before and after consumption, this experiment allowed us to determine if different tastes affect reflex reaction times.

Circuit And Synaptic Mechanisms Of Methamphetamine Induced Cognitive Deficits During Abstinence: Roles Of The Perirhinal-Prefrontal Pathway And The Nucleus Reuniens, Sarah Goldsmith

MUSC Theses and Dissertations

Cognitive deficits during abstinence are a hallmark of methamphetamine (meth) use and indicative of negative treatment outcomes. In rats, both long access meth self-administration and meth binge produce recognition memory deficits due to drug-induced plasticity within the perirhinal cortex (PRH). PRH projections are numerous and include the medial prefrontal cortex (mPFC) and the Nucleus Reuniens (NRe). In the first study, the role of the PRH-mPFC reciprocal circuit in novel object recognition memory was investigated by infusing an rgAAV encoding GFP-tagged Cre recombinase into the PRH or the mPFC. Following surgery, rats explored objects. During exploration, PRH neurons receiving input from …

Increased Neuronal Activity Restores Circadian Function In Drosophila Models Of C9orf72-Als/Ftd, Sho Inami, Benjamin P. Jenny, Oghenerukevwe Akpoghiran, Sara I. Gallagher, Alexandra K. Strich, Ayako Tonoki, Davide Trotti, Aaron R. Haeusler, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

Circadian rhythm disruptions are common across neurodegenerative diseases, but their link to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains unclear. The C9orf72 hexanucleotide repeat expansion is the most prevalent genetic cause of ALS/FTD. Here, we used Drosophila models expressing pathogenic arginine-rich dipeptides (PR or GR) or GGGGCC hexanucleotide repeats to investigate circadian deficits in C9orf72-ALS/FTD. We found that circadian rhythmicity and period length were altered in a repeat number-, dosage-, expression pattern-, and age-dependent manner. Additionally, we observed lower levels of the neuropeptide PDF, a key regulator of free-running circadian rhythms, as well as decreased projection complexity and …

How To Search For The Engram: Optogenetics And Network Dynamics, Claudia Garcia Jou

Dissertations, Theses, and Capstone Projects

Memories are thought to be encoded by ensembles of neurons called "engram cells", because their artificial activation with optogenetics leads to the behavioral expression of a memory. However, the physiological mechanisms that mediate this process remain unknown. In this thesis, I investigate how optogenetic stimulation of memory-tagged cells changes neuronal firing, spatial coding, and the geometry of neural manifolds. I used an active place avoidance task and a foraging task to label engram cells in the dorsal hippocampus with Channelrhodopsin2 (ChR2). I then recorded the hippocampal activity response to optogenetic stimulation in mice under anesthesia, head-fixed, or freely moving. I …

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) …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

The Serotonin 1b Receptor In Psilocybin’S Therapeutic-Like Mechanisms: From Behavior To Network Reorganization, Sixtine Fleury

Dartmouth College Ph.D Dissertations

Mood disorders represent a substantial and growing global health crisis, with ~10 million adults in the US meeting criteria for a major depressive disorder (MDD). Current first-line treatments such as SSRIs require long-term daily administration and fail a significant proportion of patients, driving renewed interest in rapid-acting alternatives. Psilocybin, a serotonergic psychedelic, shows growing clinical evidence of efficacy in treating depressive and anxiety disorders, often producing therapeutic effects persisting weeks to months following a single dose. Yet, the neural mechanisms underlying these enduring effects remain poorly understood and have been largely attributed to the serotonin 2A receptor (5-HT2AR) based on …

The Role Of The Amygdala In Huntington Disease-Associated Aggression, Luis Torres

Honors Undergraduate Theses

Huntington disease (HD) is a fatal neurodegenerative disorder caused by a trinucleotide CAG expansion in the huntingtin gene (HTT). HD is characterized by motor, cognitive, and psychiatric symptoms that significantly impact patient and caregiver quality of life. Psychiatric symptoms, including depression, anxiety, and irritability, are common manifestations of HD and can emerge years before the onset is clinically diagnosed. Aggression is a common and challenging psychiatric symptom in HD, often misunderstood and associated with caregiver stress, early institutionalization, and reduced quality of life. Despite its clinical impact, aggression in HD lacks effective, targeted treatment options. Similar to HD …

Assessing The Effects Of Theta Transcranial Alternating Current Stimulation During Working Memory Performance On Theta-Gamma Phase Amplitude Coupling In Healthy Adults, Samantha M. Zimmer

UNF Graduate Theses and Dissertations

Transcranial alternating current stimulation (tACS) is an emerging form of noninvasive brain stimulation with substantial effects on behavior and brain function due to its ability to entrain endogenous neural oscillations. Working memory is a cognitive process that involves holding onto information that is no longer present in the environment and manipulating or reorganizing information for immediate use. Theta oscillations are critical for the functionality of the frontoparietal network and are involved in strengthening communication and coordination between frontal and parietal brain regions, especially during working memory processing. TACS applied at the theta frequency, targets theta oscillations, strengthens network communications, and …