Neuroscience and Neurobiology Commons^™

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 Responses To Magnetic Orientation Information In Songbirds, Madeleine Ir Brodbeck

Electronic Thesis and Dissertation Repository

Effective navigation and orientation is essential for animals to survive. The study of migratory birds provides insights into these processes, particularly through mechanisms like the geomagnetic compass, which uses Earth's magnetic field for directional information. A brain region in songbirds relevant to this is cluster N, known for its potential role in processing geomagnetic information. Notably, cluster N appears exclusive to nocturnally migratory birds, being active solely at night, and lesion studies reveal that an intact cluster N is necessary for geomagnetic compass orientation. However, given the scarcity of empirical data concerning cluster N, substantial questions persist regarding its function. …

The Modulation Of Lfp Characteristics In The Freely Moving Common Marmoset, William Jm Assis

Electronic Thesis and Dissertation Repository

The hippocampus is a neural structure critical for navigation. Neurons in this region, along with others, create a functional network which generates large-amplitude modulations known as local field potential (LFP) activity. Prior LFP research has predominantly used rodent animal models, however recent studies have shown that frequencies associated with navigation in other mammals do not correlate to those of the rodent. We hypothesized that LFP characteristics in the common marmoset are modulated by the speed and axis of travel of the animal. Two marmosets were placed in a free moving 3-dimensional environment where movement and neurological activity were recorded. Results …

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 …

Characterizing The Roles Of The Variable Linker And Hub Domains In Camkii Activation, Noelle Dziedzic

Doctoral Dissertations

Learning and memory formation at the cellular level involves decoding complex electrochemical signals between nerve cells, or neurons. Understanding these processes at the molecular level requires a comprehensive study of calcium-sensitive proteins that serve as signal mediators within cells. More specifically, the protein calcium/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of downstream cellular signaling events in the brain, playing an important role in long term memory formation. CaMKII is encoded in humans on four different genes: alpha, beta, gamma and delta. For added complexity, each of these gene products can be alternatively spliced and translated into multiple protein …

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

Graduate Theses, Dissertations, and Problem Reports

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 …

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 …

Context, Goals, And Operant Behavior: The Role Of The Prelimbic Cortex And Associated Neural Circuitry, Callum Mark Piper Thomas

Graduate College Dissertations and Theses

Operant (instrumental) conditioning is a laboratory model of voluntary behavior. In its simplest form, performing a particular response, such as a lever press, leads to delivery of a reinforcing outcome (e.g., a sucrose pellet). Operant behaviors can be associated with preceding stimuli (“habits”) or outcomes (“goal-directed actions”). A factor that influences performance of operant behaviors is the context in which they are learned. Contexts can be defined as background stimuli that are present during behavior. For example, eating dessert may occur in the context of a restaurant and the sated feeling of a finished meal. The context for eating dessert, …

Deciphering The Firing Patterns Of Hippocampal Neurons During Sharp-Wave Ripples, Kourosh Maboudi Ashmankamachali

Theses and Dissertations

The hippocampus is essential for learning and memory. Neurons in the rat hippocampus selectively fire when the animal is at specific locations - place fields - within an environment. Place fields corresponding to such place cells tile the entire environment, forming a stable spatial map supporting navigation and planning. Remarkably, the same place cells reactivate together outside of their place fields and in coincidence with sharp-wave ripples (SWRs) - dominant electrical field oscillations (150-250 Hz) in the hippocampus. These offline SWR events frequently occur during quiet wake periods in the middle of exploration and the follow-up slow-wave sleep and are …

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, …

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 …

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, …

Investigation Of Memory Related Cortical Thalamic Circuitry In The Human Brain, Puck C. Reeders

FIU Electronic Theses and Dissertations

This dissertation examined the role of medial prefrontal cortex (mPFC) and the hippocampus (HC) in episodic memory, and provides a novel approach to identify the midline thalamus mediating mPFC-HC interactions in humans. The mPFC and HC are critical to the temporal organization of episodic memory, and these interactions are disrupted in several mental health and neurological disorders. In the first study, I provide evidence that the mPFC is involved in ordinal retrieval, and the HC is active in temporal context retrieval in remembering the order of when events happen. In the second study, I focus on the anatomical basis of …

Effects Of A Novel, Non-Toxic Histone Deacetylase Inhibitor On Hippocampal Memory Formation, Histone Acetylation, And Bdnf Gene Expression In Male Mice, Sarah Brianna Beamish

Theses and Dissertations

Memory dysfunction is a common symptom of aging, neuropsychiatric disorders, and neurodegenerative disorders, yet truly effective treatments for memory loss do not exist. De novo gene transcription is a molecular requirement for long-term memory formation. The transcription of genes related to synaptic plasticity and learning are regulated in part by histone acetylation, an epigenetic mechanism that regulates chromatin accessibility. Pharmacological compounds that maintain histone acetylation, called histone deacetylase inhibitors (HDACi), enhance memory by preventing deacetylation of core histone proteins, which initiates binding of transcriptional machinery to open chromatin. Therefore, HDACi are potentially promising therapeutics that could be used to prevent …

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 …

Sex Differences In The Role Of Cornichon Homolog-3 On Spatial Memory And Synaptic Plasticity, Hannah Elizabeth Frye

Arts & Sciences Electronic Theses and Dissertations

Cornichon homolog-3 (CNIH3) is an AMPA receptor (AMPAR) auxiliary protein highly expressed in the dorsal hippocampus (dHPC), a region where AMPARs are critical for spatial memory and synaptic plasticity. A 2016 genome-wide association study (GWAS) by Nelson et al. identified single nucleotide polymorphisms (SNPs) in the gene CNIH3 to be associated with reduced individual risk for the development of opioid use disorder (OUD) in individuals with prior opioid exposure. We previously demonstrated a key role for AMPARs in the dHPC in opioid-associated learning and memory, therefore we hypothesized that CNIH3 in the dHPC may mediate learning and memory processes through …

Dedicated Interneuronal Microcircuits Regulated By Behavioral State, Moises William Arriaga

Arts & Sciences Electronic Theses and Dissertations

The hippocampus is a critical brain structure for learning and memory. Neuronal inhibition within the hippocampus, performed by a wide variety of inhibitory interneuron subtypes, is required to organize and regulate the cell activity and circuit operations which underly memory formation. Despite the importance of inhibitory interneurons to the function of the hippocampus, detailed descriptions of the role of interneurons in the regulation of network activity have been limited by difficulties associated with identifying and recording from these cells using traditional electrophysiology techniques, especially in awake, behaving animals. To better investigate the function of hippocampal interneurons in awake, behaving animals, …

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 …

Placenta-Expanded Stromal Cell Therapy In A Rodent Model Of Simulated Weightlessness, Amber M. Paul, Linda Rubinstein, Charles Houseman, Metadel Abegaz, Steffy Tabares Ruiz

Publications

Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative. We found that treatment of adult female mice with PLX-PAD near the onset of simulated weightlessness by hindlimb unloading (HU, 30 d) was well-tolerated and partially mitigated decrements caused by HU. Specifically, PLX-PAD treatment rescued HU-induced thymic atrophy, and mitigated HU-induced changes in percentages of …

The Effects Of Interneuron Progenitor Cell Transplantation On Network Dynamics In An Animal Model Of Mesial Temporal Lobe Epilepsy, Willie Curry

Graduate College Dissertations and Theses

Epilepsy is associated with a very high incidence of cognitive and behavioral comorbidities that are detrimental to overall quality of life. Current treatments for epilepsy,namely anticonvulsant pharmacological agents, generally increase the amount of inhibitory drive in order to counteract the hyperexcitability observed in the disorder. However, administration of these agents, while effective for 70% of epilepsy sufferers, leave a residual 30% of patients who don’t become seizure-free. The concomitant adverse side effects of anticonvulsants - these can paradoxically include increased cognitive "fog" or confusion, automatisms, and even increased number of seizures - are a great additional concern, as is the …

Behavioral, Endocrine, And Neural Responses To Stress In Postpartum And Nulliparous Rats : Potential Mechanisms Of Postpartum Stress Resilience, Joanna Medina

Legacy Theses & Dissertations (2009 - 2024)

Major depressive disorder is one of the most pervasive psychiatric illnesses in the United States. Women are at greater risk for developing depression, particularly during their childbearing years. Approximately 17% of new mothers develop postpartum depression within 4 weeks after parturition. The risk for postpartum depression is even greater in women who do not breastfeed or stop breastfeeding early. Major depressive disorder and postpartum depression share the same symptomology and common etiological bases. Dysregulated stress responses, dopamine activity, and neuroinflammation are recognized mechanisms for depression. The transition to motherhood encompasses physiological and behavioral adaptations in the brain essential for ensuring …