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Articles 1 - 25 of 25
Full-Text Articles in Life Sciences
Dendritic Processing And Efficient Coding In The Retina, Jen-Chun Hsiang
Dendritic Processing And Efficient Coding In The Retina, Jen-Chun Hsiang
Arts & Sciences Electronic Theses and Dissertations
In early sensory systems, a copious amount of information needs to be simultaneously processed to extract salient stimulus features and compress representations for efficient transmission. My thesis addresses how the retina processes visual information to detect specific motion patterns and efficiently encode our environment for perception. Around 40 retinal ganglion cell (RGC) types in mammals send specific feature representations through their axons from the retina to the brain. RGCs are the sole source of visual information to the brain. Recent studies suggest that amacrine cells (ACs) generate feature-selective responses of RGCs, but little is known about their neuronal computations. We …
Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn
Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn
Arts & Sciences Electronic Theses and Dissertations
Neurodevelopmental disorders (NDDs) are a heterogeneous family of disorders characterized by the presence of abnormal developmental trajectories. Functional connectivity (FC) neuroimaging provides a minimally-invasive method by which to investigate the progression of these disorders and identify potential biomarkers of disease-related dysfunction for use in therapeutics’ development. My thesis work therefore took several approaches to the question of how the functional connectome reflects developmental change as well as system-wide perturbations from environmental or genetic factors. I explored the use of optical fluorescence and intrinsic signal imaging to characterize FC and stimulation-derived responses in a NDD model of perinatal exposure to selective …
Precision Diffusion Imaging To Analyze Individual-Specific Plasticity, Nicole Andrea Seider
Precision Diffusion Imaging To Analyze Individual-Specific Plasticity, Nicole Andrea Seider
Arts & Sciences Electronic Theses and Dissertations
Diffusion weighted imaging (DWI) is used to non-invasively infer and characterize the structure and integrity of the brain’s white matter fibers. Individual-specific precision diffusion imaging can identify additional organizational detail important for understanding basic brain connectivity and for advancing clinical applications of DWI in neuromodulation and neurosurgical planning. The reliability of individual specific DWI and data requirements for various analytic methodologies must first be systematically assessed. The reliability and accuracy of precision diffusion imaging was evaluated as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (Chapter 2). Parameter estimation methods that allowed …
Neural Representation In The Primary Visual Cortex Amid High Neural Variability, Ji Xia
Neural Representation In The Primary Visual Cortex Amid High Neural Variability, Ji Xia
Arts & Sciences Electronic Theses and Dissertations
Animals process high-dimensional sensory information constantly. How does neural activityin sensory cortices represent this information? Recent advances in large-scale recordings allow us to monitor activity of hundreds or thousands of neurons simultaneously across a long period of time. Population recordings showed that cortical neuronal responses to repeated sensory stimulation is highly variable from trial to trial. However, how neurons in neocortex represent sensory information amid high neural variability is not well understood. To answer this question, we used two-photon calcium imaging to record from hundreds of excitatory neurons simultaneously from mouse primary visual cortex. We analyzed neural responses to repeated …
Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu
Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu
Arts & Sciences Electronic Theses and Dissertations
The vestibular system sense gravity and self-motion to help animals maintain body balance. Although vestibular signals inform the brain of the directions and speed of our body movements, it still remains unclear how these sensory information are processed and organized in the central nervous system. My thesis aims to illustrate neural computation underlying central vestibular tuning and the topographic organization of the vestibular circuits. First I established a novel approach to perform whole-cell recording of synaptic inputs in vivo during multi-axis movements in the central vestibular neurons. This technical advance allowed me to simultaneously measure presynaptic and postsynaptic tuning, along …
Altered Network Organization And Screen Time Use In Childhood Attention-Deficit / Hyperactivity Disorder (Adhd), Elizabeth Jane Hawkey
Altered Network Organization And Screen Time Use In Childhood Attention-Deficit / Hyperactivity Disorder (Adhd), Elizabeth Jane Hawkey
Arts & Sciences Electronic Theses and Dissertations
Introduction: Symptoms of attention-deficit/hyperactivity disorder (ADHD) have been associated with alterations in functional connectivity involving networks in the developing brain that support optimal cognitive control. However, a clear profile of altered connectivity has yet to emerge, and it remains unclear whether changes in behavioral patterns such as screen time (ST) contribute to ADHD symptomatology and altered connectivity in networks that support cognitive control. The current study examined connectivity between large-scale networks associated with cognitive control (CC), measures of executive function (EF) which index CC, and ST in children with ADHD. Methods: Our sample included 11,874 children (ages 9-11, 52% male) …
Linking Neuronal Protein Phosphatase 2a To The Dlk Stress Kinase Signaling Cascade, Margaret Hayne
Linking Neuronal Protein Phosphatase 2a To The Dlk Stress Kinase Signaling Cascade, Margaret Hayne
Arts & Sciences Electronic Theses and Dissertations
Neurons are constantly responding to internal and external cues as they adapt through signaling cascades and transcriptional programs. I have identified a role for the dual leucine zipper kinase (DLK) and the transcriptional program it controls in neuronal inhibition of the protein phosphatase PP2A. PP2A is an essential phosphatase, expressed in all cell types and required for survival. There is a reduction in PP2A activity in Alzheimer’s disease patient brains which is linked to increased phosphorylation of the microtubule associated protein Tau and ultimately cell death. Here, I have demonstrated that PP2A acts to restrain the DLK stress response and …
Testing Candidate Cerebellar Presymptomatic Biomarkers For Autism Spectrum Disorder, Zoe Wilson Hawks
Testing Candidate Cerebellar Presymptomatic Biomarkers For Autism Spectrum Disorder, Zoe Wilson Hawks
Arts & Sciences Electronic Theses and Dissertations
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed on the basis of social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar-mediated error signaling impairments contribute to the causation of ASD. However, the relationship between infant cerebellar functional connectivity (fcMRI) and later ASD behaviors and outcomes has not been investigated. Such work is critical to establish early (presymptomatic) cerebellar correlates of ASD. Methods: Data from the Infant Brain Imaging Study (n=94, 68 male) were used to evaluate cerebellar fcMRI as a presymptomatic biomarker for ASD. Specifically, brain-behavior associations were analyzed for 6-month cerebellar connections in relation …
Sex Differences In The Role Of Cornichon Homolog-3 On Spatial Memory And Synaptic Plasticity, Hannah Elizabeth Frye
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 …
Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Shahriyar Majidi
Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Shahriyar Majidi
Arts & Sciences Electronic Theses and Dissertations
Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes. Despite the prevalence of this phenotypic phenomenon, an in vivo genome-scale understanding of how TFs dynamically respond within the chromatin context to paralog depletion is still lacking. We explore this question in the mammalian brain by studying the highly conserved MEF2 family of TFs, which confer phenotypic robustness for neuronal processes across multiple brain regions. The paralogous TFs MEF2A and MEF2D are strongly co-expressed in granule neurons of the cerebellum, the most abundant neurons in the brain. Employing single and double conditional knockout of MEF2A and MEF2D in …
Dissecting The Neural Circuits Mediating Pain-Induced Negative Affect And Drug-Seeking Behaviors, Tamara Markovic
Dissecting The Neural Circuits Mediating Pain-Induced Negative Affect And Drug-Seeking Behaviors, Tamara Markovic
Arts & Sciences Electronic Theses and Dissertations
Understating the function of neural circuits and the state-depended adaptations within them is one of the fundamental aims in the field of neuroscience. With recent technical developments in monitoring circuit dynamic, such as calcium (Ca2+) imaging, visualizing synaptic connections using viral approaches and manipulating neuronal activity in cell-specific manner such as optogenetic and chemogenetics, we are now able to mechanistically link the activity and function of neural circuits with behavioral outcomes.Using the above-mentioned techniques, I demonstrate that pain induces somatic adaptations in the Ventral Tegmental Area (VTA) dopamine (DA) neurons to drive anhedonia-like behaviors. Pain is a complex phenomenon composed …
The Feeling Mind, Maria Doulatova
The Feeling Mind, Maria Doulatova
Arts & Sciences Electronic Theses and Dissertations
According to standard conceptions of agency, our reasons and intentions guide our actions. That is, goal-directed intentions play a key role in practical deliberation, planning, and execution of action. Furthermore, purposeful, goal-directed behavior warrants attributions of responsibility or “reactive attitudes” like resentment, anger, gratitude and forgiveness. However, recent developments of the dual-process theory of mind cast doubt on the empirical adequacy of this picture. While people take themselves to be responding to relevant reasons, they are often bypassed by irrelevant affective or automatic reactions. In this work I go beyond the dual-process theory of mind to offer a mechanistic account …
Characterizing A Novel Metabolic Pathogenic Mechanism In Familial Hemiplegic Migraine, Sarah Elizabeth Smith
Characterizing A Novel Metabolic Pathogenic Mechanism In Familial Hemiplegic Migraine, Sarah Elizabeth Smith
Arts & Sciences Electronic Theses and Dissertations
Migraine, an episodic neurological disorder, afflicts about 1 in 10 people at least monthly, yet the underlying pathophysiological mechanisms remain poorly understood. The prototypical monogenic migraine disorder, Familial Hemiplegic Migraine, theoretically presents an excellent opportunity for preclinical modeling, but thus far animal models of migraine have failed to recapitulate the severe migraine aura symptoms of episodic paralysis and ataxia. Mutations that cause Familial Hemiplegic Migraine occur in one of three genes, two neuronal ion channels, and interestingly, the astrocytic α2-Na/K ATPase. In the case of α2-Na/K ATPase, mutations primarily result in loss of protein function. As migraine is thought to …
Apolipoprotein E Immunotherapy For The Preclinical Treatment Of Alzheimer Disease And Cerebral Amyloid Angiopathy, Monica Xiong
Apolipoprotein E Immunotherapy For The Preclinical Treatment Of Alzheimer Disease And Cerebral Amyloid Angiopathy, Monica Xiong
Arts & Sciences Electronic Theses and Dissertations
The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease (AD), a neurodegenerative disorder that leads to cognitive dysfunction and dementia. One copy of APOE ε4 increases AD risk by 3.7-fold and two copies by 12-fold, whereas APOE ε2 is protective relative to the more prevalent ε3 allele. APOE4 accelerates the progression of AD by markedly impairing amyloid-β (Aβ) clearance and promoting excess Aβ aggregation, ultimately resulting in downstream neuroinflammation, tau pathology, and neurodegeneration. Aggregated Aβ can co-deposit with the APOE protein in the brain parenchyma as neuritic plaques and in …
Dedicated Interneuronal Microcircuits Regulated By Behavioral State, Moises William Arriaga
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, …
Retinal Ganglion Cells Underlying Visual Perception And Predation In Mice, Keith Patrick Johnson
Retinal Ganglion Cells Underlying Visual Perception And Predation In Mice, Keith Patrick Johnson
Arts & Sciences Electronic Theses and Dissertations
The spike trains of retinal ganglion cells (RGCs) are the sole source of visual information to the brain. In mice, more than 40 RGC types send signals to more than 50 brain areas. RGCs that perform nonlinear operations to extract specific visual features (e.g., the motion of an object against a background) are called feature detectors. Those that linearly integrate local changes in light inten-sity are known as pixel encoders. Most mouse RGC types are feature detectors. In the first part of my dissertation, I discovered a pixel encoder RGC type in mice, the PixON-RGC. I revealed how the unique …
Glial Inflammatory Responses Regulate Neurocognitive Recovery Following Viral Encephalitis, Allison Luen Soung
Glial Inflammatory Responses Regulate Neurocognitive Recovery Following Viral Encephalitis, Allison Luen Soung
Arts & Sciences Electronic Theses and Dissertations
The concept of the brain as an immune privileged organ has been slowly shifting as an in-creasing number of studies have demonstrated that even under homeostatic conditions, commu-nication between the nervous and immune system is essential for proper brain function. Given their roles in innate and adaptive immunity, glial cells and infiltrating immune cells have been placed at the center of this communication axis. Microglia, astrocytes, and T cells have all been shown to receive and convey information to all neural cell types in a coordinated effort to re-spond to injury and infection and initiate reparative mechanisms as well as …
The Role Of Enampt-Mediated Systemic Nad+ Biosynthesis In Aging And Lifespan, Mitsukuni Yoshida
The Role Of Enampt-Mediated Systemic Nad+ Biosynthesis In Aging And Lifespan, Mitsukuni Yoshida
Arts & Sciences Electronic Theses and Dissertations
Aging is a systemic decline in tissue functions that occurs during the course of our life leading to the development of age-associated health deteriorations and ultimately to the expiration of life. Over the past few decades, population aging has become increasingly evident in many parts of the world, leading to increased prevalence of age-related disabilities and diseases. Because age is a major risk factor for many chronic diseases, extensive research effort has been spent to identify common age-associated molecular changes contributing to the pathogenesis and progression of these health issues. One such molecule identified to play a central role in …
Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu
Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu
Arts & Sciences Electronic Theses and Dissertations
Noncanonical forms of DNA methylation, especially non-CpG DNA methylation, play essential roles in the neuronal epigenome, and have only recently begun to be characterized. While most DNA methylation within mammals is found in a CG context and maintained by DNMT1, neurons contain uniquely high levels of non-CpG methylation, such that the total amounts of methylation in non-CpG contexts equals or surpasses the total amounts of methylation in CG contexts. Non-CpG methylation, unlike CpG methylation, cannot be maintained by DNMT1, and must be established by the de novo methyltransferase DNMT3A.One unique characteristic of non-CpG methylation compared to canonical CpG methylation is …
Evaluating Everyday Behaviors With Delayed And/Or Probabilistic Consequences Through A Discounting Framework, Yu-Hua Yeh
Evaluating Everyday Behaviors With Delayed And/Or Probabilistic Consequences Through A Discounting Framework, Yu-Hua Yeh
Arts & Sciences Electronic Theses and Dissertations
Delay and probability discounting refer to the decrease in subjective value of an outcome as the time until its occurrence increases and the likelihood of its occurrence decreases, respectively. Significant differences between the discounting of gains and losses, either delayed or probabilistic, have been documented in the literature. A recent study that investigated similarities and differences between the discounting of delayed gains, delayed losses, and probabilistic losses, found qualitative individual differences (i.e., subgroups) present only in the discounting of losses (Yeh et al., 2020). The current study expanded the previous investigation of subgroups to the discounting of probabilistic gains (Experiment …
Visual And Non-Visual Control Of Movement: The Role Of Proprioception In Upper Limb Function After Stroke, Nathan A. Baune
Visual And Non-Visual Control Of Movement: The Role Of Proprioception In Upper Limb Function After Stroke, Nathan A. Baune
Arts & Sciences Electronic Theses and Dissertations
This dissertation presents a series of studies into human reach and grasp, focusing on the neural systems and behaviors of upper-limb action that underly performance under varied sensory conditions: specifically, acting with and without visual feedback of the limb and under typical or impaired proprioceptive sensation (proprioceptive decline with aging and proprioceptive deficit following stroke). Under typical conditions, a combination of visual and non-visual (e.g., proprioception) sources of information are used to guide action. In the instance of stroke survivors or elderly individuals with proprioceptive deficits/decline, there may be a necessary reliance on visual information to perform. The studies are …
Understanding The Roles Of Dna Methylation And Mecp2 In Neuronal Enhancer Control, Adam Clemens
Understanding The Roles Of Dna Methylation And Mecp2 In Neuronal Enhancer Control, Adam Clemens
Arts & Sciences Electronic Theses and Dissertations
The development of organisms relies on complex spatial and temporal patterning of gene expression to define cell types and facilitate their functions. Cis-regulatory elements in our genome are responsible for the control of gene expression across tissues and cell types. Regulation of these elements themselves depends on a balance of activation and repression through epigenetic modifications and molecular regulatory components. Disruption of cis-regulatory element control is emerging as a cause of neurodevelopmental disease. An important contributor to gene regulation in development is methylation of cytosine in DNA, disruption of which has been associated with disease. Notably, while all cell types …
Relating Spontaneous Activity And Cognitive States Via Neurodynamic Modeling, Matthew Singh
Relating Spontaneous Activity And Cognitive States Via Neurodynamic Modeling, Matthew Singh
Arts & Sciences Electronic Theses and Dissertations
Stimulus-free brain dynamics form the basis of current knowledge concerning functional integration and segregation within the human brain. These relationships are typically described in terms of resting-state brain networks—regions which spontaneously coactivate. However, despite the interest in the anatomical mechanisms and biobehavioral correlates of stimulus-free brain dynamics, little is known regarding the relation between spontaneous brain dynamics and task-evoked activity. In particular, no computational framework has been previously proposed to unite spontaneous and task dynamics under a single, data-driven model. Model development in this domain will provide new insight regarding the mechanisms by which exogeneous stimuli and intrinsic neural circuitry …
Modularity Of Feedback For State-Dependent Guidance Of Navigation In Mouse Visual Cortex, Andrew M. Meier
Modularity Of Feedback For State-Dependent Guidance Of Navigation In Mouse Visual Cortex, Andrew M. Meier
Arts & Sciences Electronic Theses and Dissertations
Navigating through unpredictable environments requires an efficiently organized sensory system capable of adapting to behavioral demands. In the mammalian visual system, two adaptations which have arisen to meet these demands are parallel processing and top-down feedback of internally generated expectations and contextual information for adjusting responses to match the needs of the current behavioral task. Mouse visual cortex exhibits the latter of these organizing principles, like other mammals, in the form of a molecular layer (Layer 1) which receives feedback to contextually adapt sensory responses from the outside world. The first of these organizing principles, parallel processing streams, generally takes …
Of Mice And Toddlers: A Cross-Species Investigation Of The Social Motivation Theory Of Autism, Claire Weichselbaum
Of Mice And Toddlers: A Cross-Species Investigation Of The Social Motivation Theory Of Autism, Claire Weichselbaum
Arts & Sciences Electronic Theses and Dissertations
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social impairments and restricted, repetitive behaviors. Despite its growing prevalence, ASD remains poorly understood. One explanation for its social symptoms that has gained prominence in recent years is the Social Motivation Theory, which proposes a reduced motivation for social engagement as the underlying cause of impaired social functioning in ASD. While typically developing individuals find social interaction inherently rewarding, this theory suggests that people who develop ASD do not experience the same attraction to social stimuli and therefore miss out on critical social learning opportunities, hampering the development of …