Life Sciences 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. …

A Neural Comparison Between Mus Musculus And Monodelphis Domestica, Cristian M. Botello, John L. Vandeberg, Mario Gil

Research Colloquium

Mus Musculus is one of the first and widely used animal models in neuroscience. There are many reasons that Mus Musculus is used for research including, short generation length and large litters, but the most important reason is their mammalian brain. Another animal that is gaining interest as an animal model is the Monodelphis Domestica. The Monodelphis Domestica is a marsupial, pups are born underdeveloped and move onto the underbelly of their mothers until they reach a more mature age. One difference is the Monodelphis ventricle size is much larger in the forebrain area. Another difference is the formation of …

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 …

The Effects Of Ketones On Brain Metabolism And Cognition, Erin Reiko Saito

Theses and Dissertations

The brain is one of the most energetically demanding organs within the human body and is cognitively susceptible to energetic deficits such that the rise in obesity, insulin resistance, and Alzheimer’s disease in recent decades pose a substantial threat to cognitive longevity. The therapeutic efficacy of ketones are well-established in epilepsy and are currently being applied to other disease states. Alzheimer’s disease is characterized by impairments in brain glucose uptake and metabolism in regions relevant to learning, memory, and cognition that progress with the disease. While brain glucose uptake is impaired, ketone uptake is unaltered, potentially enabling ketones to fuel …

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 …

Differential Regulation Of Gene Expression Pathways With Dexamethasone And Acth After Early Life Seizures., Jeffrey L Brabec, Mohamed Ouardouz, J Matthew Mahoney, Rod C Scott, Amanda E Hernan

Faculty Research 2022

Early-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients' quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even …

The Ventral Hippocampus Dynamically Regulates Amygdala Encoding And Learned Fear, Matthew Richard Herbst

Dissertations (1934 -)

The nervous system has evolved a set of survival circuits optimized to respond to environmental threats. Adaptive threat responding requires learning to predict when and where a threat may occur based on available cues. Such learning depends on a distributed network of brain structures, but there is much we do not understand about how these brain areas interact to support fear memory. Addressing this gap is crucial for understanding anxiety- and fear-related disorders as dysfunction in fear learning networks is implicated in the development and persistence of pathological fear states. In my dissertation work, I used a rodent model of …

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 …

Choline Supplementation Modifies The Effects Of Developmental Alcohol Exposure On Immune Responses In Adult Rats, Jessica A. Baker, Kristen R. Breit, Tamara S. Bodnar, Joanne Weinberg, Jennifer D. Thomas

Psychology Faculty Publications

Prenatal alcohol exposure can disrupt the development of numerous systems, including the immune system. Indeed, alterations in cytokine levels may contribute to the neuropathological, behavioral, and cognitive problems, and other adverse outcomes observed in individuals with fetal alcohol spectrum disorders. Importantly, supplementation with the essential nutrient choline can improve performance in hippocampal-dependent behaviors; thus, the present study examined the effects of choline on plasma and hippocampal cytokines in adult rats exposed to ethanol in early development. From postnatal day (PD) 4-9 (third trimester equivalent), pups received ethanol (5.25 g/kg/day) or Sham intubations. Subjects were treated with choline chloride (100 mg/kg/day) …

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 …

Aiding Semantic Memory Creation With Navigational Context, Thomas Benjamin Lyle Wasden

Theses and Dissertations

While we have traditionally understood the hippocampus to be involved in memory and navigation, it also appears that it has a role in language processing, creation and prediction. An obvious explanation for this is that language is impossible if linguistic signs cannot be remembered and retrieved. Because linguistic signs are definitionally biologically neutral or arbitrary, we must use the brain's apparatus for learning and storing information from the external world to store and retrieve them. Although plausible, this explanation fails to take into account the hippocampus' role in navigation as a contributing element in the processing, storage and retrieval of …

Combined Effects Of Aerobic Exercise And 40-Hz Light Flicker Exposure On Early Cognitive Impairments In Alzheimer’S Disease Of 3×Tg Mice, Sang-Seo Park, Hye-Sang Park, Change-Ju Kim, Seung-Soo Baek, Song-Young Park, Cody Anderson, Myung-Ki Kim, Ik-Ryeul Park, Tae-Woon Kim

Health and Kinesiology Faculty Publications

Alzheimer’s disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40-Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Aβ, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-mo-old 3×Tg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 wk of exercise combined with 40-Hz …

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 …

Diabetes Mellitus Affects Working Memory, Dylone C. Braganza, Emmanuel Flores, Lauren A. Crew, Ryan A. Wirt, Andrew A. Ortiz, Adam M. Mcneela, Jefferson W. Kinney, James M. Hyman

Spectra Undergraduate Research Journal

Alzheimer’s disease (AD) degrades the brain’s ability to remember, think, and carry out tasks. The exact cause is not known, but several risk factors have been identified, including diabetes mellitus (DM). DM causes elevated blood sugar levels due to reduced insulin production in the pancreas. The linkage between elevated glucose levels and the behavioral impairments are not fully understood, which was the focus of this study. Rats were trained to alternate directions in a maze to receive a reward on consecutive trials. After training, five rats were injected with streptozotocin (STZ), which induces hyperglycemia by injuring pancreatic beta cells. Three …