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 …

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 …

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 …

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 …

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) …

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 …

Parvalbumin Interneuron-Oligodendrocyte Interactions In The Infralimbic Cortex Promote Extracellular Plasticity Mechanisms After Safety Learning, Lucy Emma Denholtz

Dissertations, Theses, and Capstone Projects

The ability to differentiate between threat and safety cues is essential for adaptive behavior, yet this process is disrupted in psychiatric disorders, such as post-traumatic stress disorder (PTSD), where safety cues fail to downregulate fear expression. To better understand the neurobiological mechanisms of safety learning, I investigate how safety conditioning vs contextual fear conditioning modify behavioral and cellular mechanisms in the infralimbic (IL) region of the medial prefrontal cortex (mPFC) at several time points after learning. Through this work, I identify a novel mechanism whereby safety learning promotes learning dependent neuro-glial interactions that promote conditions for plasticity in the mPFC. …

Neural Mechanisms Of Context-Sensitive Behavior In The Adult Male Zebra Finch, Katherine L. Anderson

Dissertations, Theses, and Capstone Projects

Adapting behaviors to the perceived external environment is key to the success and survival of individuals in social species. This context-sensitive modulation of behavior is critical for informative interactions with conspecifics, like alerting a neighbor to a nearing predator or capturing the attention of a potential mate. For the adult male zebra finch (Taeniopygia guttata), a vocal-learning songbird, context-sensitive adaptions to a learned song are key for developing and maintaining pair-bonds with females who are extremely attentive to subtle modulations of song structure. In this thesis, I explore the hypothesis that the influence of a social behavior network …

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 …

A Neuroimmune Circuit Mediates Chemo Brain Pathology, Daniel Ahmadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapeutic agents, while effective in targeting malignant tumors, often reduce the patients’ quality of life by inducing fatigue, pain, and motivational deficits. These symptoms are collectively referred to as “chemo brain.” The mechanisms underlying these adverse effects, and specifically whether fatigue and motivational impairments share a common etiology, remain poorly understood. The neural–immune substrates of these symptoms remain obscure, in part because standard preclinical regimens either bypass key systemic signals or introduce local toxicity confounds. Here, I establish and validate a three‑day, low‑dose intravenous cisplatin protocol that avoids peritoneal inflammation and severe renal injury yet produces robust, reversible fatigue and …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Neural Activity Within And Between Visual And Executive Areas Is Modulated Post-Locomotion In Rhesus Macaques, Sergey Egranov

Dissertations and Theses (Open Access)

Physical activity has been shown to benefit cognitive and mental health by improving cerebrovascular perfusion and regulating hormone-mediated processes on a systemic level. However, the acute effects of physical activity, such as locomotion, on the neuronal circuits underlying cognitive processes have yet to be fully characterized. This body of work seeks to rectify this gap in knowledge through analysis of how both behavioral performance and neuronal activity signatures in visual and executive brain regions are modulated post-locomotion in rhesus macaques.

To this end, we performed high-yield electrophysiological recordings simultaneously from area V4, a mid-tier visual cortical region, and the dorsolateral …

Characterization Of A Descending Neuron That Modulates Flight Performance And Provides Input Onto A Flight-Related Predictive Motor Circuit, Andisheh Balouchi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Descending neurons (DNs) play a critical role in sensorimotor integration by relaying motor information to the ventral nerve cord (VNC). Within the VNC, local interneurons, other DNs, and ascending neurons (ANs) make circuits with sensory and motor neurons to modify flies’ behavior. One important AN pair in Drosophila Melanogaster is mesothoracic ascending histaminergic neurons (MsAHNs), which are known to convey predictive wing motor signals to the brain. DNg32 is the primary upstream synaptic partner of MsAHNs, integrating DNg32 input with other inputs to generate predictive motor signals. The goals of this study were to 1) map the synaptic connectivity of …

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 …

Local Geometry Of Elementary Visual Computations, Peter Neri

MODVIS Workshop

Visual operators (e.g. edge detectors) are classically modelled using small circuits involving canonical computations, such as template-matching and gain control. Circuit models explain many aspects of the empirical descriptors that are used to characterize local visual operators, from sensitivity to classification images. Notwithstanding their utility, these models fail to provide a unified framework encompassing the variety of effects observed experimentally, such as the impact of contrast, SNR, and attention on the above descriptors. My goal is to start with a simple, plausible geometrical representation of the perceptual operation carried out by the observer, and to show that this representation is …

Mapping The Neural Circuits That Underlie Metabolic Vs. Emotional Regulation Of Food-Seeking Behavior, Xu Zhang

Dissertations and Theses (Open Access)

Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food …

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations and Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …

Cortical Representation Of Learning Social Interactions In Freely Moving Non-Human Primates, Melissa Franch

Dissertations and Theses (Open Access)

The motivation and capacity to be social is necessary for human survival. Successful learning of complex, prosocial behavior stems from the ability to perceive and respond to visual cues, such as the body language and facial expressions, from others in our environment. This dependence on visual information to guide social interaction is especially true for humans and non-human primates. Although recent studies in primate neurophysiology discovered neurons that can encode socially relevant variables, like reward and social actions, the underlying neural mechanisms of learning advanced social concepts, such as cooperation, are not well understood. Further, previous work has identified …

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 …

Connectivity Of Amygdala Somatostatin-Expressing Neurons And Their Role In Taste-Guided Behavior., Jane Jeruto Bartonjo

Electronic Theses and Dissertations

The nucleus of solitary tract (NST) and parabrachial nucleus (PBN) represent the first and second central synapses of ascending gustatory information. Neural processing in these nuclei is influenced by descending input from forebrain regions such as the central nucleus of the amygdala (CeA). In mice, we have shown that somatostatin (Sst) expressing neurons of CeA that project to NST and PBN are largely distinct cell populations and optogenetic inhibition of the CeA/Sst-to-NST subpopulation increases the intake of high concentrations of quinine with no apparent effect on sucrose intake. Synaptic connectivity of these cells is needed to understand the possible mechanisms …

Activity Dynamics Of The Nucleus Accumbens Neurons During Natural And Drug Reward Seeking, Reda M. Chalhoub

MUSC Theses and Dissertations

The nucleus accumbens core (NAc) represents a major neural substrate of reward encoding that has been found to play a role in differentially regulating natural and drug rewards, including cocaine. Its constituent D1- and D2- receptor expressing medium spiny neurons (MSN) are alternatively hypothesized to have either opposing effects on reward seeking or a shared role in forming encoding “ensembles” – a sparsely activated population of neurons that encode reward associations- that coordinate behavioral responding to rewards and cues predicting reward availability. Previous methods used to study these neuronal populations failed to temporal quantify the cell-type specific activity in reward …

Active Encoding Of Space Through Time, Michele Rucci, Jonathan D. Victor

MODVIS Workshop

No abstract provided.

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Oral Contraceptives And Affective Disorders: Neurobiology And Informed Choice, Sophia Mae Drezner

Scripps Senior Theses

Pregnancy prevention and female reproductive freedom have been some of the most contested political issues for decades. Abortion, a fundamental part of women’s healthcare, divides liberals and conservatives on an international scale. The consequences of unintended pregnancy without safe and reliable contraception are widespread, disproportionately impacting women of color, trans and non-binary folks, and poorer communities. The birth control pill is the most common form of oral contraception (OC) globally. Many people with ovaries begin the pill or other hormonal contraceptive (HC) methods as young as 11 years old. Exogenous progesterone and estrogen are known to impact mood, affect, physiology, …

Meta-Analytic Connectivity Modelling Of Healthy Swallowing, Chris R. Tilton

Honors Theses and Capstones

A quantitative, voxel-wise meta-analysis was performed to investigate the brain regions involved in healthy human swallowing. Studies included in the meta-analysis (1) examined water swallowing, saliva swallowing, or both, (2) included healthy, normal subjects, and (3) reported stereotaxic brain activation coordinates in standard space. Following these criteria, a systematic literature review identified 8 studies that met the criteria. An activation likelihood estimation (ALE) meta-analysis and meta-analytic connectivity modelling (MACM) analysis were performed with BrainMap software. Ten clusters with high activation likelihood were found in the bilateral precentral gyri, right insula, left declive, right medial frontal gyrus, right dorsal nucleus of …