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Optimization Of Orthogonal Translation Systems Enhances Access To The Human Phosphoproteome, Jack Michael Moen Oct 2021

Optimization Of Orthogonal Translation Systems Enhances Access To The Human Phosphoproteome, Jack Michael Moen

Yale Graduate School of Arts and Sciences Dissertations

Protein phosphorylation is a ubiquitous post-translational modification that governs signaling cascades and protein-protein interactions. Orthogonal translation systems, in which an orthogonal aminoacyl-tRNA synthetase and tRNA pair have been repurposed for insertion of a non-standard amino acid, have been developed for co-translational insertion of phospho-amino acids. Here, we systematically developed variants of phosphoserine and phosphothreonine orthogonal translation systems to minimize cellular toxicity and maximize translational fidelity. We characterized novel tRNA constructs to enhance cellular fitness and change decoding functionality. Multiple genetic background strains were developed to enhance the incorporation of phospho-amino acids into recombinant proteins. Utilizing large-scale DNA synthesis, we were …

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The Roles Of Polyploidy, Climate, And Genetic Architecture In The Evolution Of Leaf Form In Viburnum (Adoxaceae), Morgan Kirstin Moeglein Oct 2021

The Roles Of Polyploidy, Climate, And Genetic Architecture In The Evolution Of Leaf Form In Viburnum (Adoxaceae), Morgan Kirstin Moeglein

Yale Graduate School of Arts and Sciences Dissertations

Plants exhibit extensive variation in leaf form, but the evolutionary drivers of this variation are not well understood. This dissertation leverages the wide diversity of leaf form and instances of leaf syndrome convergence in Viburnum to investigate trends in leaf trait evolution across the group. First, I explore how changes in chromosome number and genome size influence leaf characters of ecophysiological importance. It appears that even with extensive variation in chromosome number and genome size across Viburnum, nucleotypic changes largely do not constrain leaf traits related to ecophysiological function. I then look into a case of convergent evolution for leaf …

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On Neuroscience-Inspired Statistical And Computational Problems, Zifan Li Oct 2021

On Neuroscience-Inspired Statistical And Computational Problems, Zifan Li

Yale Graduate School of Arts and Sciences Dissertations

Recent years have witnessed a surge of problems lying at the intersection of statistics andneuroscience. In this thesis, we explore various statistical and computational problems that are inspired by neuroscience. This thesis consists of two main parts, each inspired by a different system in the brain. In the first part, we study problems related to the visual system. In Chapter 2, we investigate the problem of estimating the collision time of a looming object using a theoretical formulation based on statistical hypothesis testing. In Chapter 3, we build computational models for the compound eye of Drosophila, and analyze how the …

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Characterization Of Postoperative Recovery After Cardiac Surgery- Insights Into Predicting Individualized Recovery Pattern, Makoto Mori Oct 2021

Characterization Of Postoperative Recovery After Cardiac Surgery- Insights Into Predicting Individualized Recovery Pattern, Makoto Mori

Yale Graduate School of Arts and Sciences Dissertations

Understanding the patterns of postoperative recovery after cardiac surgery is important from several perspectives: to facilitate patient-centered treatment decision making, to inform health care policy targeted to improve postoperative recovery, and to guide patient care after cardiac surgery. Our works aimed to address the following: 1) to summarize existing approaches to measuring and reporting postoperative recovery after cardiac surgery, 2) to develop a framework to efficiently measure patient-reported outcome measures to understand longitudinal recovery process, and 3) to explore ways to summarize the longitudinal recovery data in an actionable way, and 4) to evaluate whether addition of patient information generated …

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Investigating The Effect Of Allostery On Downstream Biology Of The Epidermal Growth Factor Receptor, Deepto Mozumdar Oct 2021

Investigating The Effect Of Allostery On Downstream Biology Of The Epidermal Growth Factor Receptor, Deepto Mozumdar

Yale Graduate School of Arts and Sciences Dissertations

The Epidermal Growth Factor Receptor (EGFR) is a member of the receptor tyrosine kinase (RTK) family of human proteins with a critical role in transducing diverse extracellular chemical information to initiate multiple cellular signaling cascade in the cell that are essential for normal cell development. Aberrant activation of this receptor via mutation or overexpression misregulates this flow of information and is implicated in a multiple human carcinoma. Thus, understanding the molecular mechanisms by which chemical information is encoded and decoded in EGFR is imperative both from a basic cell biology and therapeutic standpoint. In this thesis consisting of four chapters, …

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Investigation Of Nuclear Pore Complex Assembly And Nuclear Envelope Growth In C. Elegans Embryos, Michael Sean Mauro Oct 2021

Investigation Of Nuclear Pore Complex Assembly And Nuclear Envelope Growth In C. Elegans Embryos, Michael Sean Mauro

Yale Graduate School of Arts and Sciences Dissertations

The nucleus is the defining organelle of eukaryotic cells and compartmentalizes the genome from the rest of the cytoplasm. Compartmentalization is achieved by the nuclear envelope (NE), which is comprised of the inner and outer nuclear membranes. At fusion points are nuclear pore complexes (NPCs), which facilitate the transport of macromolecules across the NE. In metazoan cells that undergo open mitosis, the NE and NPCs disassemble to allow for chromosome segregation. With the completion of mitosis, the process must be reversed, and a new nucleus is formed. How thousands of NPCs rapidly assemble to form a functional NE is not …

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Integrating Genomics With The Fossil Record To Explore The Evolutionary History Of Echinoidea, Nicolas Mongiardino Koch Oct 2021

Integrating Genomics With The Fossil Record To Explore The Evolutionary History Of Echinoidea, Nicolas Mongiardino Koch

Yale Graduate School of Arts and Sciences Dissertations

Echinoidea constitutes one of five major clades of living echinoderms, marine animals uniquely characterized by a pentaradial symmetry. Approximately 1,000 living and 10,000 extinct species have been described, including many commonly known as sea urchins, heart urchins and sand dollars. Today, echinoids are ubiquitous in benthic marine environments, where they strongly affect the functioning of biodiverse communities such as coral reefs and kelp forests. Given the quality of their fossil record, their remarkable morphological complexity and our thorough understanding of their development, echinoids provide unparalleled opportunities to explore evolutionary questions in deep-time, providing access to the developmental and morphological underpinnings …

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Improving Surveillance Of Emerging Rna Viruses, Mary E. Petrone Oct 2021

Improving Surveillance Of Emerging Rna Viruses, Mary E. Petrone

Yale Graduate School of Arts and Sciences Dissertations

Effective surveillance of emerging RNA viruses is essential for public health andepidemiological research. Without identifying incident infections in an actionable time frame, the prevention of future infections becomes nearly impossible. This was exemplified at the beginning of the COVID-19 pandemic in the United States, during which time only a small fraction of infected individuals was detected through surveillance, and the virus promptly spread across the country. Similarly, parameterizing informative epidemiological models requires accurate data. In the absence of effective surveillance and/or a clear understanding of where gaps in the system exist, efforts to better understand the dynamics of circulating viruses …

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The Rheology Of Striated Muscles, Khoi Dac Nguyen Oct 2021

The Rheology Of Striated Muscles, Khoi Dac Nguyen

Yale Graduate School of Arts and Sciences Dissertations

Striated muscles are actuators of animal bodies. They are responsible for several biomechanical functions critical to survival and these include powering the cardiovascular system and modulating the mechanical interactions the body has with its surroundings. Nearly two centuries of active research on muscle phenomena has led to detailed insights into its microscopic composition, but accurate predictive models of muscle at larger scales remain elusive. This thesis reports on efforts to accurately capture the mechanical properties of striated muscles based on current knowledge of actomyosin dynamics. Specifically, this thesis derives the rheology of striated muscles from the dynamics. Muscle rheology is …

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Cost-Effectiveness Analyses Of Typhoid Interventions In Epidemic And Endemic Settings, Maile Thayer Phillips Oct 2021

Cost-Effectiveness Analyses Of Typhoid Interventions In Epidemic And Endemic Settings, Maile Thayer Phillips

Yale Graduate School of Arts and Sciences Dissertations

Background: Typhoid fever is a major source of morbidity and mortality in developing countries, accounting for approximately 12-21 million infections, 119,000-269,000 deaths, and 2-23 million disability-adjusted life years (DALYs) annually. Typhoid fever is caused by infection with the bacteria Salmonella enterica serovar Typhi, which is mainly transmitted through fecal contamination of food or water. Due to these modes of transmission, most cases occur in low- and middle-income countries (LMICs) where sanitary conditions are poor and access to clean water and sanitation is not common. However, the scale of disease incidence is uncertain. Studies suggest that facility-based laboratory-confirmed estimates, the numbers …

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Development Of The Nuclear-Electronic Orbital Method For Applications To Molecular Electrocatalyst Systems, Patrick Schneider Oct 2021

Development Of The Nuclear-Electronic Orbital Method For Applications To Molecular Electrocatalyst Systems, Patrick Schneider

Yale Graduate School of Arts and Sciences Dissertations

Studies of molecular electrocatalysts often involve input from quantum chemical computations in the pursuit of catalyst design targeting several desirable features. To this end, conventional density functional theory (DFT) calculations have proven to be a good match with a reasonable balance between computational accuracy and cost. However, a multicomponent method that treats select nuclei on the same quantum mechanical level as electrons would be useful for a more proper treatment of nuclear quantum effects. Such a multicomponent DFT method has been developed in recent years within the nuclear-electronic orbital (NEO) framework. However, for the multicomponent method to be practically applied …

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Synthetic Studies Towards The Total Synthesis Of (–)-Lomaiviticin A, John A. Rose Oct 2021

Synthetic Studies Towards The Total Synthesis Of (–)-Lomaiviticin A, John A. Rose

Yale Graduate School of Arts and Sciences Dissertations

(–)-Lomaiviticin A (1) is a complex C2-symmetric bacterial metabolite which was isolated from a fermentation broth of Salinispora DPJ-19 by He and co-workers in 2001. The structure of 1 was proposed through detailed analysis of NMR spectral data (Figure 1). Due to the presence of a diazotetrahydrobenzo[b]fluorene substructure, 1 belongs to a family of natural products often referred to as “diazofluorenes” among which the kinamycins (A, C, and F seen in Figure 1) are the earliest known members. (–)-Lomaiviticin A (1) is the most cytotoxic member of the diazofluorene family known with half maximal inhibitory potencies (IC50S) in the nanomolar …

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Interactions Among Species And Ecosystems Determine Their Responses To Scale-Specific Fluctuations, Franz Wesley Simon Oct 2021

Interactions Among Species And Ecosystems Determine Their Responses To Scale-Specific Fluctuations, Franz Wesley Simon

Yale Graduate School of Arts and Sciences Dissertations

Ecosystems are highly connected systems with many interacting components. Understanding the mechanisms creating ecosystem patterns requires an explicit consideration of the scales at which interactions among species and their environments occur. This dissertation focuses on the scale of temporal variability and how temporal variability is incorporated into communities’ dynamics. I first derive an abstract theory that describes the general patterns of variability propagation within communities. Next, I explore the role of species’ interaction strengths on community dynamics across time scales. Finally, I study the impact of human-induced hydrological changes of the Guadalquivir River on the European anchovy fishery in the …

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Synergistic Action Of Synaptotagmin Family In Neurotransmitter Release., Ekaterina Stroeva Oct 2021

Synergistic Action Of Synaptotagmin Family In Neurotransmitter Release., Ekaterina Stroeva

Yale Graduate School of Arts and Sciences Dissertations

The overarching theme of my thesis work is centered around the understanding of how the Synaptotagmin (Syt) family of proteins, which are key players in neurotransmission, is regulated in the brain. Upon very briefly introducing other key molecular players, firstly, I summarize the discovery of the regulation of Syts by self-oligomerization. This work is focused on the characterization of the physiologically relevant Syt1 ring-like oligomers, which are formed in the presence of negatively charged lipids and dissociate upon calcium binding. Using the approach of hypothetical structure-guided mutagenesis, phenylalanine in position 349 is identified as critical for the oligomer formation. Importantly, …

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Biological Mechanisms Linking Stress And Anhedonia, Colin Stanton Oct 2021

Biological Mechanisms Linking Stress And Anhedonia, Colin Stanton

Yale Graduate School of Arts and Sciences Dissertations

Evidence from research across species suggests that stress exposure is linked with anhedonia (loss of pleasure and/or decreased motivation). However, the mechanisms through which stress might impact anhedonia remain unclear. Chapters 1 and 2 of this dissertation review putative etiological pathways from stress to anhedonia and discuss stressor characteristics that could inform experimental models of stress-induced anhedonia. Chapter 3 describes an attempt to identify which types of stress are most associated with anhedonia using stress interview data from multiple datasets. Unexpectedly, we found no credible effects on anhedonic symptoms for stressor chronicity, severity, dependence on behavior, or interpersonal focus. Instead, …

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Specifying And Targeting Cognitive-Affective Dysfunctions In Antisocial Individuals, Allison Mary Stuppy-Sullivan Oct 2021

Specifying And Targeting Cognitive-Affective Dysfunctions In Antisocial Individuals, Allison Mary Stuppy-Sullivan

Yale Graduate School of Arts and Sciences Dissertations

Antisocial behavior includes a wide range of behaviors that violate social norms, from criminal acts to substance misuse. The adverse consequences of antisocial behavior produce a great physical and emotional burden on perpetrators, victims, and family members. This burden is not addressed adequately, with incarceration being the most common intervention for antisocial behavior. When individuals who chronically engage in antisocial behavior are offered therapeutic treatments, the majority neither complete nor benefit from them. One reason existing treatments do not fully address antisocial behavior is because they do not consider or target cognitive-affective dysfunctions driving such behavior, and mechanistic research, to …

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Proteome-Wide Screening For Mitogen-Activated Protein Kinase Docking Motifs And Interactors, Guangda Shi Oct 2021

Proteome-Wide Screening For Mitogen-Activated Protein Kinase Docking Motifs And Interactors, Guangda Shi

Yale Graduate School of Arts and Sciences Dissertations

AbstractProteome-wide screening for mitogen-activated protein kinase docking motifs and interactors Guangda Shi 2021 Kinases catalyze the transfer of phosphate to substrates, a reaction critical for many cellular events. Mitogen-activated protein kinases (MAPKs), including ERK, p38, and JNK, phosphorylate hundreds of substrates, and each plays a pivotal role in distinct processes such as cell growth, survival, differentiation, and apoptosis. To correctly respond to external stimuli, MAPKs use several mechanisms to achieve a high degree of selectivity for their target substrates. A critical aspect of MAPK specificity comes from docking interactions occurring between sites distal from the site of catalysis and short …

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On The Role Of Stability In Animal Morphology And Neural Control, Neelima Sharma Oct 2021

On The Role Of Stability In Animal Morphology And Neural Control, Neelima Sharma

Yale Graduate School of Arts and Sciences Dissertations

Mechanical stability is vital for the fitness and survival of animals and is a crucial aspect of robot design and control. Stability depends on multiple factors, including the body's intrinsic mechanical response and feedback control. But feedback control is more fragile than the body's innate mechanical response or open-loop control strategies because of sensory noise and time-delays in feedback. This thesis examines the overarching hypothesis that stability demands have played a crucial role in how animal form and function arise through natural selection and motor learning. In two examples, finger contact and overall body stability, we investigated the relationship between …

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Characterizing Photophysics Of Photoconvertible-Fluorescent Protein Meos3.2 For Quantitative Fluorescence Microscopy, Mengyuan Sun Oct 2021

Characterizing Photophysics Of Photoconvertible-Fluorescent Protein Meos3.2 For Quantitative Fluorescence Microscopy, Mengyuan Sun

Yale Graduate School of Arts and Sciences Dissertations

Photoconvertible fluorescent proteins (PCFPs) are widely used in super-resolution microscopy, and studies of cellular dynamics. Their photoconversion properties have enabled single-molecule localization microscopy (SMLM) by temporally separating closely-spaced molecules. However, our understanding of their photophysics is still limited, hampering their quantitative application. For example, counting fluorescently-tagged fusion proteins from the discrete localizations of individual molecules is still difficult. The red-to-green photoconvertible fluorescent protein mEos3.2 is favored by many due to its monomeric property, high brightness, photostability, compatibility with live cells, and 1:1 labeling stoichiometry. The fluorescent protein mEos3.2 is fused to the coding sequence of a protein of interest in …

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Immune Activation By Novel Allobaculum Species Reveals Reciprocal Epistasis Among Human Gut Commensals, Tyler A. Rice Oct 2021

Immune Activation By Novel Allobaculum Species Reveals Reciprocal Epistasis Among Human Gut Commensals, Tyler A. Rice

Yale Graduate School of Arts and Sciences Dissertations

Gut commensal microbes that elicit human immune responses are noteworthy for their ability to influence both local mucosal inflammation and, more rarely, systemic antibody responses. Here we isolated and characterized novel strains belonging to genus Allobaculum from inflammatory bowel disease (IBD) stool samples. In defined gnotobiotic mouse models we recapitulated the inflammatory effects of Allobaculum sps. and their notable induction of systemic immune responses at baseline. A microbial ecology screen revealed that this taxon is inversely correlated with Akkermansia muciniphila, and co-colonization experiments uncovered microbe-dependent redirection of immune phenotypes, which we term reciprocal epistasis. These immunostimulatory gut commensal strains exemplify …

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Regulation Of Tim-3 By Phosphatidylserine, Courtney Mccaul Smith Oct 2021

Regulation Of Tim-3 By Phosphatidylserine, Courtney Mccaul Smith

Yale Graduate School of Arts and Sciences Dissertations

TIM-3, or T cell, immunoglobulin, and mucin domain-containing protein-3, is a transmembrane glycoprotein expressed by several types of immune cells, including T cells, making it an important regulator of the immune response. However, the biology of TIM-3 is complicated, as it has been shown to variously promote and inhibit the function of T cells and other immune cells. Understanding the contexts in which TIM-3 serves these dual roles has remained difficult, as the ligands that regulate the activity of this receptor are still unclear. Several molecules have been proposed to regulate TIM-3, including phosphatidylserine (PS), galectin-9, carcinoembryonic antigen-related cell adhesion …

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Structural Studies On Mechanisms Of Samhd1 Function And Dysfunction, Joshua Temple Oct 2021

Structural Studies On Mechanisms Of Samhd1 Function And Dysfunction, Joshua Temple

Yale Graduate School of Arts and Sciences Dissertations

Sterile α-motif and HD domain-containing protein 1 (SAMHD1) is a pivotal enzyme that maintains cellular nucleotide homeostasis. SAMHD1 forms a tetramer upon binding GTP and a dNTP at allosteric sites, activating its triphosphohydrolase activity against substrate deoxynucleoside triphosphates (dNTPs). This dNTPase activity, in combination with other functions in DNA repair, cell cycle regulation, and nucleic acid binding, is important to other facets of SAMHD1 biology as a critical mediator of antiviral defense, cancer suppression, and autoimmune regulation. An array of post-translational modifications on SAMHD1 present an additional layer of functional regulation – most notably phosphorylation at residue T592, a master …

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Development Of Diverse Bifunctional Molecules For Interrogating Dcps, Her3, Brachyury, And Phosphorylation-Driven Diseases Towards Therapeutic Applications, Jake Charles Swartzel Oct 2021

Development Of Diverse Bifunctional Molecules For Interrogating Dcps, Her3, Brachyury, And Phosphorylation-Driven Diseases Towards Therapeutic Applications, Jake Charles Swartzel

Yale Graduate School of Arts and Sciences Dissertations

Technologies that hijack cellular pathways using bifunctional small molecules have recently risen to the forefront of the drug discovery world. The first targeted protein degradation (TPD) technology to be developed, PROteolysis Targeting Chimeras (PROTACs), were disclosed two decades ago. The recent successes of AR and ER-degrading PROTACs in pioneering clinical trials has propelled interest in developing novel platforms to further expand the druggable proteome and the arsenal of strategies that are available for therapeutic intervention. This thesis is focused on the development of novel bifunctional molecules that enable interrogation of diseases driven by traditionally challenging protein targets. The first chapter …

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Elucidating The Molecular Mechanism Of Cis-Regulation By The Long Noncoding Rna Lincrna-P21, Lauren Nicole Winkler Oct 2021

Elucidating The Molecular Mechanism Of Cis-Regulation By The Long Noncoding Rna Lincrna-P21, Lauren Nicole Winkler

Yale Graduate School of Arts and Sciences Dissertations

Pervasive transcription is a hallmark of mammalian genomes. Although protein-coding genes span only a small fraction of the genome, more than two-thirds is transcribed, yielding thousands of noncoding transcripts whose expression exhibits a tight correlation with cell type, disease state, and other biological phenomena. A subset of these transcripts, termed long noncoding RNAs (lncRNAs) on account of their length (>200 nucleotides) and lack of apparent coding potential, have been shown to play functional roles in processes ranging from immune signaling to organogenesis. In contrast to trans-acting lncRNAs, which may operate in either the nucleus or cytoplasm, cis-acting lncRNAs remain …

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Graph Priors, Optimal Transport, And Deep Learning In Biomedical Discovery, Alexander Tong Oct 2021

Graph Priors, Optimal Transport, And Deep Learning In Biomedical Discovery, Alexander Tong

Yale Graduate School of Arts and Sciences Dissertations

Recent advances in biomedical data collection allows the collection of massive datasets measuring thousands of features in thousands to millions of individual cells. This data has the potential to advance our understanding of biological mechanisms at a previously impossible resolution. However, there are few methods to understand data of this scale and type. While neural networks have made tremendous progress on supervised learning problems, there is still much work to be done in making them useful for discovery in data with more difficult to represent supervision. The flexibility and expressiveness of neural networks is sometimes a hindrance in these less …

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Learning, Optimization And Data Translation With Deep Neural Networks, Ganlin Song Oct 2021

Learning, Optimization And Data Translation With Deep Neural Networks, Ganlin Song

Yale Graduate School of Arts and Sciences Dissertations

Neural networks have been intensively studied as machine learning models and widely applied in various areas. This thesis investigates three problems related to the theory and application of neural networks. First, we analyze a learning scheme for neural networks that uses random weights in the backpropagation training algorithm, which is considered to be more biologically plausible than the standard training procedure. We establish theory that shows the convergence of the loss and the alignment between the forward weights of the network and the random weights used in the backward pass. Second, we study a family of optimization problems where the …

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Development Of Enantioselective Synthetic Routes To (–)-Myrocin G And (–)-Euonyminol., Martin Tomanik Oct 2021

Development Of Enantioselective Synthetic Routes To (–)-Myrocin G And (–)-Euonyminol., Martin Tomanik

Yale Graduate School of Arts and Sciences Dissertations

In the first chapter, I describe the development of a synthetic strategy towards (–)-myrocin G (8), the putative active form of the antiproliferative fungal metabolite (+)-myrocin C (4). Myrocin C (4) has been proposed to cross-link DNA by two-fold nucleotide addition; however, this proposed bioalkylation hypothesis has not been tested with native DNA. Our synthetic efforts provided a highly convergent total synthesis of myrocin G (8) in 15 steps from simple starting materials. A key steps in the sequence involved a carefully designed fragment coupling–cyclization cascade (see 85 + 89 → 90). This transformation effectively unites the iodocyclopropane 85 with …

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Electrochemical Hydrogen Peroxide Generation With Anthraquinone Chemistry For Advanced Oxidation Process, Qianhong Zhu Oct 2021

Electrochemical Hydrogen Peroxide Generation With Anthraquinone Chemistry For Advanced Oxidation Process, Qianhong Zhu

Yale Graduate School of Arts and Sciences Dissertations

Hydrogen peroxide plays a critical role in many industrial applications, including chemical synthesis and environmental remediation. For example, in advanced oxidation process of water treatment, hydrogen peroxide is activated to hydroxyl radical by catalysts or UV light for non-selective and rapid degradation of non-biodegradable, toxic, recalcitrant organic micropollutants. Industrial anthraquinone process, which synthesizes hydrogen peroxide from hydrogen and oxygen gas in organic phase, requires intensive capital investment, expensive reactants, high energy inputs, and raises many environmental concerns. Electrochemical production of hydrogen peroxide with air, water and electricity as inputs has emerged as a promising alternative method because it is low-cost, …

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A Fundamental Exploration Of The Interactions Between Minerals And Life’S Building Blocks In Deep Time, Jasmina Wiemann Oct 2021

A Fundamental Exploration Of The Interactions Between Minerals And Life’S Building Blocks In Deep Time, Jasmina Wiemann

Yale Graduate School of Arts and Sciences Dissertations

Complex organic matter is the most abundant form of organic carbon in the fossil record on Earth and in geological materials delivered from Space. It is unclear how complex organic matter preserved in fossils and meteorites forms in different terrestrial and extraterrestrial geological settings. The molecular make-up of decay-resistant organic polymers in fossils and meteorites has the potential to preserve biological signals and record geological conditions in deepest time. Carbonaceous fossil morphologies resembling cells, extracellular matrix and entire tissue architectures have provided pivotal insights into the evolutionary history of life. Fossil soft tissues within vertebrate hard tissues have been a …

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Developmental Participation Of Vip Interneurons In Cortical Dynamics, Daniel Barson Oct 2021

Developmental Participation Of Vip Interneurons In Cortical Dynamics, Daniel Barson

Yale Graduate School of Arts and Sciences Dissertations

In the mammalian cerebral cortex, local and long-range synaptic connections are believed to relay information related a diverse array of cognitive, emotional, and physiological functions to influence the computations performed by single neurons. While the anatomical connectivity of a single neuron is static on short timescales, its functional involvement in distributed networks may fluctuate rapidly to subserve moment-to-moment changes in behavior. A sparse class of interneurons that express vasoactive intestinal polypeptide (VIP) has been hypothesized to mediate these fluctuations by modulating the gain of cortical micro-circuits in response to neuromodulatory and long-range cortico-cortical inputs. To test this hypothesis, we developed …

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