Neuroscience and Neurobiology Commons^™

Exposure To Manganese During Juvenile Development Increases Microglial Activation In The Hippocampus Following Systemic Infection With A/California/04/2009 Influenza A H1n1 Virus, Megan Hager, Adam Schuller, Omar Yanouri, Collin Bantle, Richard Smeyne, Ronald Tjalkens

Farber Institute for Neuroscience Faculty Papers

Up to 80% of patients with Parkinson’s Disease (PD) develop dementia within 20 years of diagnosis. Although the etiology of PD and related neurodegenerative disorders is poorly understood, risk factors including environmental toxicants and viral infections are linked to disease onset and progression. Exposure to high doses of the essential element, manganese (Mn), causes neurotoxicity associated with parkinsonian symptoms and cognitive impairment in humans. Additionally, epidemiologic studies indicate that viral infections increase risk of developing PD. Previously, our lab demonstrated that mice exposed to Mn during juvenile development showed greater neuroinflammatory changes in microglia within the substantia nigra following systemic …

Neuroimaging Correlates Of Differences In Learning From Repeated Probabilistic Outcomes, Allison E. Rudolph

CMC Senior Theses

Learning from experience requires integrating feedback over time, yet individuals vary widely in how effectively they extract structure from probabilistic environments. This study examined how such variability relates to neural responses in the ventral striatum (vStr), caudate nucleus, hippocampus, and medial prefrontal cortex (mPFC). Seventy-four participants across childhood, adolescence, and adulthood completed a modified Iowa Gambling Task during fMRI scanning, choosing whether to play or pass on four machines differing in expected value and variance. Behavioral learning slopes, calculated across six runs for each machine, were used to classify participants as learners or non-learners. Learners showed clearer improvement over time …

Acute And Chronic Effects Of Neuroinflammation On Hippocampus And Anterior Cingulate Cortex Network Dynamics, Lauren A. Crew

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neuroinflammation has emerged as a critical modulator of cognitive function and neural circuit dynamics, yet the distinct contributions of acute and chronic neuroinflammation to brain function remain poorly defined. This dissertation examines how inflammation independently alters large-scale neural activity and behavior, focusing on interactions between the hippocampus (HPC) and anterior cingulate cortex (ACC), regions essential for memory and executive processes. Using in vivo electrophysiological techniques in a rodent model, this study compares the effects of short-term (acute) and prolonged (chronic) neuroinflammatory states, induced via Poly I:C, on neural oscillations, regional coherence, and spatial coding. Findings reveal that even transient inflammation …

Enduring Efffects Of Juvenile Fluoxetine Exposure On Serotonin Transporter Expression Within The Hippocampus And Prefrontal Cortex Of Male C57bl/6 Mice, Daniel Eduardo Calvo

Open Access Theses & Dissertations

Prescription rates of fluoxetine, the most dispensed selective serotonin reuptake inhibitor, have been rising among the juvenile population. Since adolescence is a critical developmental period in which the brain undergoes pruning, chronic increases in serotonin levels may lead to long-term neurobiological changes in brain regions responsible for emotional regulation. Thus, using mice as a model system, this thesis evaluated how adolescent fluoxetine exposure (AFE) influences the expression of serotonin transporters (SERT) in the adult hippocampus and prefrontal cortex. To do this, postnatal day (PD)-35 male C57BL/6 mice were administered with fluoxetine (250 mg/l in their drinking water) for 15 consecutive …

Investigation Of Rna-Binding Protein Expression Changes In The Hippocampus Following Doxorubicin And Cyclophosphamide Treatment, Lijie Chen

Dissertations and Theses

This study investigated the molecular mechanisms underlying chemotherapy-induced cognitive impairment (CICI) following doxorubicin and cyclophosphamide treatment in a rat model, revealing three significant alterations in hippocampal tissue: selective downregulation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) (21% decrease, p=0.0298), compromised astrocytic network integrity evidenced by reduced GFAP-positive area in cornu ammonis 3 (CA3) (24%, pB=0.026) and dentate gyrus (DG) (19%, pB=0.027) regions, and elevated cellular senescence marker p19Arf specifically in DG (69%, pB=0.033) and CA3 (27%, pB=0.024). The inverse relationship between hnRNPA1 reduction and p19Arf elevation suggests a potential mechanistic link between RNA dysregulation and senescence induction, with pronounced vulnerability in …

Neural Correlates Of Socially Rewarding Memories In Posttraumatic Stress Disorder, Kyle P. Blidy

MUSC Theses and Dissertations

Significance. Memory disturbances for emotional content are central to PTSD, yet most research focuses on trauma memories. Recent evidence suggests that enhancing access to positive memories could improve mood, affect regulation, self-esteem, and integration of trauma memories. However, the neurocognitive mechanisms underlying positive memory encoding in PTSD are poorly understood. No study has examined memory for positive social items in PTSD, which is important because PTSD entails social withdrawal and reduced accessibility to positive memory. Additionally, positive memories embedded in a social context have enhanced subjective value and strengthening their accessibility may confer greater benefits to wellbeing compared to non-social …

Robust And Generalizable Representations In The Hippocampus, Hung-Tu Chen

Dartmouth College Ph.D Dissertations

An intelligent system must balance generalizing across similar experiences with maintaining the distinctiveness of each experience. This thesis explores how the hippocampus manages this balance through its neural representations to support adaptive behavior. In Chapter 1, I provide an overview of key hippocampal phenomena that contribute to this process, including remapping, splitter signal, and replay. In Chapter 2, I challenge the concept of random remapping by showing that it is possible to predict, better than chance, how a given experience will be encoded in the hippocampus across different subjects. This suggests that encoding of related experiences, which was previously thought …

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 …

How Does Schizophrenia Affect The Expression Of Alpha 7 Nicotinic Acetylcholine Receptors In The Brain?, Shruti Varshney, Nimish Acharya

Rowan-Virtua Research Day

Schizophrenia (SZ) is a psychiatric disorder with a pathophysiology that has not yet been fully understood. This mental illness is characterized by disruptions in cognition, social activity, affect, and perception, and affects approximately 0.085% of individuals worldwide. The Alpha 7 Nicotinic Acetylcholine Receptor (α7nAChR) has been connected to auditory function gating deficits. The purpose of this review is to understand the current literature in how the levels of α7nAChR expression and function are affected by SZ, information that could be used to develop therapies to modulate auditory hallucinations in patients with SZ. A literature search was conducted for peer-reviewed journal …

Alpha 7 Nicotinic Acetylcholine Receptor Expression In The Hippocampus Of Patients With Schizophrenia, Shruti Varshney, Ananya Nethikunta, Minjal Patel, Mary Kosciuk, Randel L. Swanson, Venkat Venkataraman, Robert Nagele, Eric Goldwaser, Nimish K. Acharya

Rowan-Virtua Research Day

Background: Schizophrenia (SZ) is a heterogenous psychiatric condition characterized by disruptions in cognition, social activity, affect, and perception often associated with a varied combination of positive and negative symptoms. The pathophysiology behind SZ remains poorly elucidated. Earlier reports have cited the importance of the alpha 7 nicotinic acetylcholine receptors (α7nAChR) in the hippocampus and the receptor’s association with auditory sensory gating and cognitive function. Specifically, variations in the expression and functionality of α7nAChR can be linked to auditory hallucinations experienced by patients with SZ and several therapies have been researched that target α7nAChRs. However, there are very few primary research …

Role Of The Anti-Viral Immune Response In Neural Cell Modulation And Neurological Sequelae Of Childhood Viral Infections, Yashika Kamte

Electronic Theses and Dissertations

Viral infections of the central nervous system (CNS) often result in neurological sequelae and are considered a risk factor for the development of neurological disease. Moreover, the outcomes of a viral infection are largely dependent on the age of the host, with younger hosts developing more profound neuropathology. Perhaps the developing brain coupled with an immature immune system contributes to worse outcomes in the very young. Children suffering from brain infections are more prone to develop enduring neurological impairments even after recovery from the infection. Although majority of the brain growth occurs in utero, neurodevelopment continues throughout the juvenile …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …

Neural Damage Following Francisella Tularensis Infection, Anahis Tena

Open Access Theses & Dissertations

This dissertation investigates the impact of Francisella tularensis infection on the brain, focusing on its anatomical localization, effects on synaptic health, and behavioral and cognitive consequences in mice. Employing a combination of fluorescent tagging, confocal and light sheet microscopy, the study first maps bacterial foci within the brain, anticipating a concentration in the limbic system, particularly the hippocampus. Subsequently, it examines synaptic function post-infection using calcium imaging in various neuronal cultures, expecting a decrease in calcium signaling indicative of synaptic impairment. Finally, behavioral assays like the forced swim test, object recognition test, and Morris Water Maze assess the cognitive and …

An Erp Measure Of Non-Conscious Memory Reveals Dissociable Implicit Processes In Human Recognition Using An Open-Source Automated Analytic Pipeline, Richard J. Addante, Javier Lopez-Calderon, Nathan Allen, Carter Luck, Alana Muller, Lindsey Sirianni, Cory S. Inman, Daniel L. Drake

Psychology Student Publications

Non-conscious processing of human memory has traditionally been difficult to objectively measure and thus understand. A prior study on a group of hippocampal amnesia (N = 3) patients and healthy controls (N = 6) used a novel procedure for capturing neural correlates of implicit memory using event-related potentials (ERPs): old and new items were equated for varying levels of memory awareness, with ERP differences observed from 400 to 800 ms in bilateral parietal regions that were hippocampal-dependent. The current investigation sought to address the limitations of that study by increasing the sample of healthy subjects (N = …

Morphological Characterization Of Two Transgenic Strategies For Genetic Access To Semilunar Granule Neurons In The Mouse Dentate Gyrus, David T. Rexford

Masters Theses

Granule cells (GCs) of the dentate gyrus (DG) have been understood as a homogeneous class of neurons exhibiting a characteristic limited firing pattern. A subtype of GC called a semilunar granule cell (SGC) has been identified exhibiting variant morphology, electrophysiology, and positioning from normal GCs. SGCs represent an emerging novel subpopulation of GCs, however, there is presently no genetic tool to access SGCs separately from normal GCs. To provide access for future in vivo studies of this population, we examined two genetic strategies for putative SGC specificity in mouse brain slices. Morphological analysis was performed for quantitative identification of putative …

Glutamate, And Its Relationship To Task-Induced Functional Connectivity In The Human Brain: A Focus On Schizophrenia, Kathleen Liu Young, John Kopchick, Jeffrey Stanley, Vaibhav Diwadkar

Medical Student Research Symposium

Glutamate is the brain’s major excitatory neurotransmitter mediating both neuroplasticity and network function (Zhou & Danbolt, 2014). Basal glutamate (Glu) measured using proton magnetic resonance spectroscopy (1H-MRS) provides insight into a region’s density of neuropil related to the glutamatergic system. Moreover, given the role of glutamate in mediating brain network function, Glu levels may play a role in the brain’s functional connectivity (FC), which is typically estimated from functional magnetic resonance imaging (fMRI) time series data. These questions converge when considering the clinical syndrome of schizophrenia (SCZ). Patients with SCZ show abnormalities in basal Glu in the hippocampus and prefrontal …

Hyperparameter Codependence In Fieldnet: Guidelines For Ann Construction, Seiji Akera

Pitzer Senior Theses

Artificial Neural Networks (ANNs) comprise a non-linear modeling method that is often used to analyze neural data in place of linear models. These networks fall under one of two classifications: pure prediction purposes and improving understanding of the brain through neural interpretability. FieldNet is an ANN designed by Dr. Gautam Agarwal that takes complex valued theta oscillations recorded from implanted multi-electrodes and predicts the rat’s location as it moves throughout a maze. In learning neural features to make this classification, FieldNet appears to reconstruct place fields. The construction of FieldNet has an impact on both the performance and reconstruction capabilities …

Artificial Light At Night Disrupts Pain Behavior And Cerebrovascular Structure In Mice, Jacob Raymond Bumgarner

Graduate Theses, Dissertations, and Problem Reports (ETD)

Artificial Light at Night Disrupts Pain Behavior and Cerebrovascular Structure in Mice

Jacob R. Bumgarner

Circadian rhythms are intrinsic biological processes that fluctuate in function with a period of approximately 24 hours. These rhythms are precisely synchronized to the 24- hour day of the Earth by external rhythmic signaling cues. Solar light-dark cycles are the most potent environmental signaling cue for terrestrial organisms to align internal rhythms with the external day. Proper alignment and synchrony of internal circadian rhythms with external environmental rhythms are essential for health and optimal biological function.

The modern human environment on Earth is no longer …

Spatial Representation In Postrhinal Cortex, Patrick Lachance

Dartmouth College Ph.D Dissertations

Animals rely on a variety of internal and external cues to orient themselves when navigating their environments and determining their current spatial context. Information regarding these cues enters the brain from the navigator’s first-person perspective. Information of this type is considered to be egocentric, or self-centered. However, decades of behavioral, electrophysiological, and imaging research suggest that the brain contains a rich collection of spatial representations that are unrestricted by the animal’s first-person perspective, and instead are defined relative to the surrounding environment. These representations are considered allocentric, or world-centered. Despite an abundance of promising modeling work, the specific mechanisms by …

Mirnas Levels In A Streptozocin Model Of Alzheimer’S Disease, Nada Moustafa

Theses and Dissertations

Dementia entails a progressive decrease in cognitive functions, with 50%-75% of cases attributed to Alzheimer’s disease (AD); an aging-associated condition characterized by the build-up of tangled phosphorylated Tau (p-Tau) protein and beta-amyloid (Aβ) depositions. Sporadic AD (sAD) is multifactorial in nature, resulting from a combination of environmental and genetic predisposing factors. Type 2 diabetes mellitus (T2DM) is a leading risk factor for dementia, and deregulation of brain glucose metabolism is associated with early cognitive affection in sAD. Thus, the diabetogenic agent Streptozotocin (STZ) is used to experimentally create an AD model in animals (STZ-induced sAD), in which abnormalities in cerebral …

Examining Limbic Sexual Dimorphisms In Schizophrenia, Kennedy S. Madrid

Undergraduate Honors Theses

Schizophrenia is a mental disorder that affects a significant number of individuals in the United States and can have numerous different symptoms. Recently, interest in the differences between the neuroanatomy of individuals with schizophrenia and individuals without schizophrenia has emerged, specifically the sexual dimorphism in individuals with schizophrenia. This study aimed to gain a better understanding of the sexual dimorphisms of two structures in the limbic system: the hippocampus and amygdala. Data was harmonized and analyzed from two datasets to determine the sexual dimorphic factor of these structures in healthy controls and individuals with schizophrenia. Demographic features were also taken …

Withdrawal From Voluntary Oral Methamphetamine Reveals Female Specific Susceptibilities To Behavioral Deficits And Neurochemical Perpetuators Of Neurotoxicity And Drug Seeking Behavior, Nicoletta K. Memos

Dissertations, Theses, and Capstone Projects

MA is a potent, highly addictive psychomotor stimulant known to produce neurotoxic effects on the brain leading to neurological impairments^1-6 characterized by neurodegeneration of dopaminergic fibers, cell bodies and pathways, as well as brain regions such as the hippocampus, frontal cortex, and midbrain^1,5.

In MA addiction, women are more vulnerable to the behavioral and cognitive effects of MA compared to men. Adult human literature reveals gender differences in usage patterns and women demonstrate increased vulnerability to the neurotoxic effects and health effects of MA use. Women begin drug use at an earlier age, escalate drug use quicker, …

The Effects Of Astrocytic Derived Insulin-Like Growth Factor (Igf-1) On Cognition And Astrocytes, Destiny Wilson

Honors Theses

Insulin-like growth factor 1 (IGF-1) is a neuroendocrine signaling hormone that plays a vital role in growth and development, as well as learning and memory. Inhibition of this hormone results in cognitive impairments like those seen with age-related decline. While a majority of research has focused on the role of IGF-1 on neurons, the role of astrocytes still needs to be explored. Our research investigates how astrocytes and cognition are affected as a result of direct regulation of localized IGF-1 production in early development and after puberty. Preliminary studies in our laboratory established a connection between IGF-1 and glial fibrillary …

Case Study: Effects Of Ultrasonic Vocalizations On Rat Behavior And Place Cell Remapping In The Hippocampus, Qingli Hu

Honors Scholar Theses

Spatial information is known to be encoded in the hippocampus, and small changes in the environment can alter the way that it is represented by our hippocampal place cells in a process called remapping. Hearing is an important sense that can be used to orient ourselves and react to the environment accordingly. In this case study, a rat model is used to test the effects of emotional auditory stimuli, behaviorally significant ultrasonic vocalizations (USVs) (50 kHz, emitted during play; 22 kHz, emitted during danger), on rat behavior on a linear track and place cell remapping in the hippocampus. Behaviorally, it …

Therapeutic Treatment With The Anti-Inflammatory Drug Candidate Mw151 May Partially Reduce Memory Impairment And Normalizes Hippocampal Metabolic Markers In A Mouse Model Of Comorbid Amyloid And Vascular Pathology, David J. Braun, David K. Powell, Christopher J. Mclouth, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Neuroscience Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop …

Investigating Mechanisms Of Injury And Intervention In A Novel In Vitro Model Of Traumatic Brain Injury In Organotypic Hippocampal Slice Cultures, Julia Elaine Jagielo-Miller

Theses and Dissertations--Psychology

Traumatic brain injuries (TBIs) impact millions of individuals each year and can pose long term consequences. Despite numerous attempts, no medication has been approved by the FDA to treat TBIs. The causes of these failed trials are multifaceted, but in part can be attributed to the complex nature of TBIs, as well as a lack of sufficient pre-clinical data. In vitro models of TBI are an important tool to help understand the cellular changes seen following the injury, in a highly controlled environment. For the following experiments, a novel model of TBI was used to injure organotypic hippocampal slice cultures, …

Contributions Of Emotion Regulation And Brain Structure And Function To Adolescent Internalizing Problems And Stress Vulnerability During The Covid-19 Pandemic: A Longitudinal Study, David G. Weissman, Alexandra M. Rodman, Maya L. Rosen, Steven Kasparek, Makeda Mayes, Margaret A. Sheridan, Lilliana J. Lengua, Andrew N. Meltzoff, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Background: Adolescence is a period of increased vulnerability for internalizing problems, particularly following stressful life events. We examined how emotion regulation and brain structure and function were associated with internalizing problems during the COVID-19 pandemic and moderated the association between pandemic-related stressors and internalizing problems. Methods: Data are from a longitudinal sample (N = 145, age range, 10–15 years) strategically assessed at 3 crucial time points: before the COVID-19 pandemic, early during the stay-at-home order period, and again 6 months later. We examined associations of amygdala and hippocampal volume and amygdala activation during an emotional processing task before the pandemic, …

Long-Term Effects Of Adolescent Fluoxetine Exposure On Hippocampal Gene Expression In Male C57bl/6 Mice, Anapaula Themann

Open Access Theses & Dissertations

Mood-related disorders, including depression and anxiety, are prevalent among children and adolescents. This poses a public health challenge, given their adverse impact on these young populations. Treatment with the selective serotonin reuptake inhibitor fluoxetine (FLX) is the first line of pharmacological intervention in pediatric patients suffering from affect-related illnesses. Although the use of this antidepressant has been deemed efficacious in the juvenile population, the enduring neurobiological consequences of adolescent FLX exposure are not well understood. For this reason, we explored for persistent molecular adaptations, in the adult hippocampus, as a function of adolescent FLX pretreatment. To do this, we administered …

Targeting Ampa Receptor Modulation During Early Life Adversity: A Mediator For Threat Associated Memories, Roseanna M. Zanca

Dissertations, Theses, and Capstone Projects

Early life adversity (ELA) is the exposure to a single or to multiple traumatic events before the age of 18 that go beyond the child’s coping. These adverse events are often exacerbated during adolescence particularly when cognitive performance is compromised. Adolescents who experienced ELA may show symptoms of post-traumatic stress disorder (PTSD), while not vividly recalling the early life trauma. These individuals show atypical connectivity between prefrontal-amygdala and hippocampus, all of which is associated with an increased risk of experiencing a traumatic event again later in life. While clinical research has increasingly stressed the importance in addressing the long-lasting consequences …

The Neurobiological Relationship Between Childhood Maltreatment And Major Depressive Disorder (Mdd), Morgan Clinton

Global Tides

Childhood maltreatment compromises healthy development, impacts neurobiology, and is associated with lasting alterations to emotional perception, processing, and regulation. Most significantly, childhood maltreatment increases the risk for later development of emotional disorders such as major depressive disorder (MDD). The stress associated with both childhood maltreatment and MDD can lead to lasting alterations to the fronto-limbic circuitry. Using functional and structural magnetic resonance imaging, researchers have observed hippocampal atrophy and amygdala hyperresponsiveness in participants who’ve experienced both childhood maltreatment and MDD. Furthermore, researchers have also observed increased connectivity between the hippocampus and amygdala in victims of childhood maltreatment. Because childhood maltreatment …