Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Accelerometry, multivariate analysis, rehabilitation, stroke, supervised machine learning, upper extremity (1)
- Adolescence, event-related potential, reward learning, reward positivity, social feedback, socioeconomic status (1)
- Alpha-synuclein, CRISPR screen, Frontotemporal dementia, proteopathic seeding, TDP-43, Valosin Containing Protein (1)
- Alzheimer disease, amyloid-beta, Apolipoprotein E, astrocyte, microglia (1)
- Alzheimer disease, amyloid-beta, MRI, neuroimaging, PET, tau (1)
-
- Alzheimer's Disease, Circadian Rhythms, Glia, Neuroinflammation, Parkinson's Disease (1)
- Alzheimer's disease, Amyloid, Genetics, Stem cells (1)
- Analgesia, Descending Modulation, Nociception, Optogenetics, Periaqueductal Gray, Rostral Ventromedial Medulla (1)
- Anxiety, Gtf2ird1, neurodevelopmental, sensorimotor, sociability, Williams Syndrome (1)
- Basal Forebrain (1)
- Binocularity, retina, superior colliculus, vision (1)
- Constraint, Disuse, fMRI, Plasticity, Resting-state (1)
- Epigenetics, Long genes, MeCP2, Rett Syndrome, Topoisomerase IIB, Transcription (1)
- Functional connectivity, local field potential, magnetic resonance imaging, neurohemodynamic coupling, NMDA receptor, oxygen polarography (1)
- Neural Learning (1)
- Novelty (1)
- Recency (1)
- Salience (1)
- Surpise (1)
Articles 1 - 15 of 15
Full-Text Articles in Medicine and Health Sciences
Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones
Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones
Arts & Sciences Electronic Theses and Dissertations
K+ homeostasis is important for maintaining healthy, physiological levels of neuronal activity. Glial cells play a central role in maintaining homeostatic ion gradients. In previous work from our lab, we unravel a glial K+ buffering program that is centered on a key kinase, salt-inducible kinase 3 (SIK3). SIK3-HDAC4 signaling in glial regulates the transcription of channels and transporters involved in water and ion transport. Defects in this pathway lead to peripheral nerve edema, neuronal hyperactivity, and seizure sensitivity. In an hyperexcitability mutant, eag Shaker, we show this pathway is downregulated and genetic activation suppresses seizure behavior. In this thesis, I …
Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan
Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan
Arts & Sciences Electronic Theses and Dissertations
The survival of a species is inextricably linked to its ability to successfully navigate and interact with its surroundings, whether to seek safety from predators or gain sustenance from prey. Both functions are performed by mice, guided by vision, and rely on intricate processing in the retina and subcortical targets in the brain. This dissertation addresses how specific features of the visual environment and specific retinal ganglion cell circuits that sample a particular space in the visual environment are used to guide efficient predation in mice.Recent studies have begun to link the ability to detect, track, and ultimately capture prey …
Emerging Insights Into A Role For Topoisomerase Iib And Methyl-Cpg Binding Protein 2 In Regulating Neuronal Transcription, Sabin Nettles
Emerging Insights Into A Role For Topoisomerase Iib And Methyl-Cpg Binding Protein 2 In Regulating Neuronal Transcription, Sabin Nettles
Arts & Sciences Electronic Theses and Dissertations
The mammalian brain has unparalleled diversity of cell types with distinct molecular, morphological, connectional and functional properties. The specialization of these cells occurs during development through a series of spatially and temporally controlled changes in gene expression that are critical for proper assembly and function. Neurons in particular have complex and elaborate gene regulatory systems which allow specific combinations of genes to be expressed at distinct levels and at discrete developmental stages, giving rise to heterogenous neuronal subtypes. Identifying unique neuronal gene regulatory factors that contribute to the dynamic changes in gene expression are critical to understanding the molecular mechanism …
The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan
The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan
Arts & Sciences Electronic Theses and Dissertations
The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …
The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland
The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland
Arts & Sciences Electronic Theses and Dissertations
The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …
Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard
Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard
Arts & Sciences Electronic Theses and Dissertations
The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …
Behavioral, Neural, And Psychiatric Correlates Of Responses To Social Feedback, Brent Rappaport
Behavioral, Neural, And Psychiatric Correlates Of Responses To Social Feedback, Brent Rappaport
Arts & Sciences Electronic Theses and Dissertations
Problems responding to peer feedback and disrupted interpersonal relationships arise in numerous psychiatric disorders; yet heterogeneity and homogeneity across disorders suggests both common and unique mechanisms of impaired social function. Identifying brain correlates of these disruptions could help explain diagnostic comorbidities as well as unique pathways, thus informing more individualized treatments. However, studies seeking to understand the link between psychological and neural mechanisms often have to rely on reverse inference assumptions to match psychological processes to brain activity. One hypothesis is that social feedback is processed similar to other forms of feedback (e.g., monetary). Thus, we aimed to test such …
Salience Coding In The Basal Forebrain And The Heterogeneous Underpinnings Underlying Novelty Computations, Kaining Zhang
Salience Coding In The Basal Forebrain And The Heterogeneous Underpinnings Underlying Novelty Computations, Kaining Zhang
McKelvey School of Engineering Theses & Dissertations
Humans and animals are consistently learning from the environment by interacting with it and getting feedback from their actions. In the environment, some objects are more important than others, because they are associated with reward, uncertainty, surprise, or novelty etc. These objects are salient to the animal. Salient objects attract attention and orientation, increase arousal, facilitate learning and memory, and affect reinforcement learning and credit assignment. However, the neural basis to support these effects is still not fully understood.We first studied how the basal forebrain, one of the principal sources of modulation of the neocortex, encodes salience events. We found …
Disuse-Driven Plasticity In The Human Brain, Dillan James Newbold
Disuse-Driven Plasticity In The Human Brain, Dillan James Newbold
Arts & Sciences Electronic Theses and Dissertations
Brain circuits are shaped and maintained by active use. We blocked use of motor circuits in three adult participants by constraining the dominant upper extremity in a cast for two weeks, causing loss of strength and fine motor function. Daily resting-state functional magnetic resonance imaging (rs-fMRI) collected for 42-64 days before, during and after casting revealed two sets of changes in brain function. First, large, spontaneous pulses of activity occurred in the disused motor circuits. Pulses showed a consistent pattern of propagation through the disused circuits— occurring earliest in the dorsal anterior cingulate cortex (dACC) and supplementary motor area (SMA), …
Validation, Categorizing, And Prediction Of Upper Limb Outcomes After Stroke, Jessica Barth
Validation, Categorizing, And Prediction Of Upper Limb Outcomes After Stroke, Jessica Barth
Arts & Sciences Electronic Theses and Dissertations
The incidence and costs of stroke in the United States are projected to rise over the next decade because of the aging population. Declining stroke mortality over the past few decades means that more people survive stroke and live with physical, cognitive, and emotional disability. Stroke remains one of the leading causes of disability in the United States because very few survivors experience a full recovery of their upper limb. Upper limb recovery after stroke is critical to performing activities of daily living and physical and occupational therapies are one of the only treatment options to address these challenges. The …
Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales
Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales
Arts & Sciences Electronic Theses and Dissertations
Endogenous analgesic pathways embody a potential target for the development for chronic pain therapies. Previous studies have demonstrated the role of the ventrolateral periaqueductal gray (vlPAG) in descending pain modulation. It has been proposed that tonic GABAergic neurotransmission at the level of the vlPAG serves to inhibit efferent excitatory projections that mediate descending analgesia. Disinhibition of these projection neurons allows subsequent activation of rostral ventromedial medulla (RVM) neurons that inhibit nociception at the level of the spinal cord. However, lack of cell-type specificity in these studies has prevented the determination of the role of specific subsets of vlPAG neurons in …
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Arts & Sciences Electronic Theses and Dissertations
Alzheimer’s disease (AD) is the leading cause of dementia and is pathologically defined by the aggregation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Rare heritable mutations within the genes for amyloid precursor protein (APP) and presenilin 1 (PSEN1), and presenilin 2 (PSEN2) cause early onset AD and account for approximately 1% of AD cases. While the majority of AD cases are late-onset (LOAD), which is defined by a markedly more complex genetic architecture that is comprised of many genetic risk factors that influence AD through multiple cellular pathways. The advent of deep sequencing analyses have allowed for the identification …
Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu
Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu
Arts & Sciences Electronic Theses and Dissertations
Protein inclusions such as β-amyloid, tau, α-synuclein, and TDP-43 are considered the pathologic hallmarks of many neurodegenerative diseases. These proteins are prone to misfold, aggregate, and template new aggregates. Accumulating evidence suggests that those proteins in their high-molecular-weight forms can serve as a "seed", spread through an interconnected brain network, and induce new inclusions. Therefore, it is essential to understand the mechanism of proteopathic seeding. In this dissertation, we performed a whole genomic CRISPR-Cas9 KO screening to identify gene modifiers of αS seeding. Within the screening, we found several hits of endolysosomal function and trafficking, including VCP. VCP is a …
Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough
Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough
Arts & Sciences Electronic Theses and Dissertations
The overall goal of this dissertation is to gain a better understanding of how current Alzheimer disease pathologic progression models interact with sources of individual-level variation in pathology to influence overall disease progression in a clinically meaningful way. Many sources of variation, both internal (e.g., genetic mutations, heterogeneity of tau pathology) and external (e.g., diet and exercise, sleep quality), are known to influence disease progression and symptom onset in AD. With the advent of therapies that have shown successful reduction of amyloid load in trials and the rapid progression of anti-tau therapies, we hypothesize that a better understanding of how …
Cell-Type Specific Expression Of Apolipoprotein E By Astrocytes And Microglia: Implications For The Development Of Amyloid-Β Pathology In Alzheimer Disease, Thomas Mahan
Arts & Sciences Electronic Theses and Dissertations
Alzheimer disease (AD) is characterized by two main pathological hallmarks, extracellular amyloid plaques primarily comprised of the amyloid-β (Aβ) peptide, and intracellular neurofibrillary tangles mainly comprised of the tau protein. Although the pathologies underlying AD were first described over one hundred years ago, researchers today are still trying to understand how the development of Aβ pathology is regulated in the hopes of developing more effective treatments. Advances in genetics over the last several decades have allowed for several genetic risk factors to be identified that increase or decrease ones likelihood for developing (AD). Of these genetic risk factors, the strongest …