Recursos de colección

DSpace at MIT (104.280 recursos)

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Brain and Cognitive Sciences - Ph.D. / Sc.D.

Mostrando recursos 1 - 20 de 315

  1. The amygdala in value-guided decision making

    Jaime-Bustamante, Kean (Kean Willyams)
    The amygdala is a structure well known for its role in fear and reward learning, but how these mechanisms are used for decision-making is not well understood. Decision-making involves the rapid updating of cue associations as well as the encoding of a value currency, both processes in which the amygdala has been implicated. In this thesis I develop a strategy to study value-guided decision making in rodents using an olfactory binary choice task. Using a logistic regression model, I show that the value of expected rewards is a strong influence on choice, and can bias perceptual decisions. In addition, I...

  2. Memory and locality in natural language

    Futrell, Richard Landy Jones
    I explore the hypothesis that the universal properties of human languages can be explained in terms of efficient communication given fixed human information processing constraints. I argue that under short-term memory constraints, optimal languages should exhibit information locality: words that depend on each other, both in their interpretation and in their statistical distribution, should be close to each other in linear order. The informationtheoretic approach to natural language motivates a study of quantitative syntax in Chapter 2, focusing on word order flexibility. In Chapter 3, I show comprehensive corpus evidence from over 40 languages that word order in grammar and...

  3. Interrogation of CRISPR-Cas targeting specificity for mammalian genome engineering

    Scott, David (David Arthur)
    Class II CRISPR-Cas RNA programmable DNA endonucleases enable high efficiency genome editing across the biological diversity for research, industrial, and biomedical applications. Human genome editing with CRISPR-Cas just recently made its debut in human clinical trials and has immense therapeutic potential to fix disease-causing mutations at the level of DNA. Ensuring the integrity and safety of research, industrial, and biomedical applications of CRISPR-Cas necessitates efficient, versatile, and comprehensive methods to evaluate of the specificity of genome editing. Here, we optimize the efficiency and characterize the targeting specificity of SpCas9 to ensure robust cleavage activity while minimizing off-target activity in human...

  4. Neurobiological mechanisms underlying episodic memory retrieval

    Roy, Dheeraj
    Memory is a central function of the brain and is essential to everyday life. Memory disorders range from those of memory transience, such as Alzheimer's disease, to those of memory persistence, such as post-traumatic stress disorder. To treat memory disorders, a thorough understanding of memory formation and retrieval is critical. To date, most research has focused on memory formation, with the neurobiological basis of memory retrieval largely ignored due to experimental limitations. Here, I present our recent advances in the study of memory retrieval using technologies to engineer the representation of a specific memory, memory engram cells, in the brain....

  5. Spiking and oscillatory correlates of visual short-term memory for multiple items

    Kornblith, Simon (Simon John)
    The richness of visual experience far exceeds our ability to remember what we have seen. However, it is unclear what neural mechanisms give rise to these limits to visual short-term memory capacity. Here, we measured neural activity in a change localization task, in which monkeys viewed two displays of multiple colored squares separated by a brief delay, and made a saccade to the square that changed color between displays. In chapter 2, we examine local field potentials in the lateral intraparietal area (LIP), frontal eye field, and lateral prefrontal cortex (PFC). At stimulus encoding, lower frequency oscillations decreased in power...

  6. Mechanisms of tissue-specific regeneration in planarians

    LoCascio, Samuel Alexander
    How animals establish and maintain the sizes of myriad tissues and organs in tight proportion to one another is a fundamental question of developmental biology. Planarian flatworms regenerate from diverse injuries, in each case precisely restoring body parts to their appropriate proportions. Underlying this ability is a pluripotent population of dividing cells called neoblasts, which are required for homeostatic maintenance and regeneration of all planarian tissues. Whether neoblasts restore proportion by sensing and responding to the presence or absence of specific tissues during regeneration is unknown. We used the planarian eye lineage to address this problem. Following decapitation, neoblasts normally...

  7. Modulation of Huntington's disease-associated phenotypes by the striatal-enriched transcription factor Foxp2

    Hachigian, Lea June
    Huntington's disease (HD), the most common inherited neurodegenerative disorder, is caused by mutations in the huntingtin (HTT) gene, which encodes a poly-glutamine (polyQ) repeat protein. Despite widespread expression of the HTT gene, HD presents with massive neuronal cell loss and transcriptional dysregulation primarily in the striatum and deep layers of the cortex. Synaptic dysfunction and motor deficits are also prominent in HD patients as well as mouse models. In an attempt to identify factors that could both explain these alterations and mirror these vulnerability patterns, we identified a potential role for the striatal-enriched polyQ protein Foxp2 in HD. The transcription...

  8. Sensorimotor transformation and information coding across cortex during perceptual decisions

    Pho, Gerald N. (Gerald Norman)
    Perceptual decision-making is an important and experimentally tractable paradigm for uncovering general principles of neural information processing and cognitive function. While the process of mapping sensory stimuli onto motor actions may appear to be simple, its neural underpinnings are poorly understood. The goal of this thesis is to better understand the neural mechanisms underlying perceptual decision-making by exploring three major questions: How is decision-relevant information encoded across the cortex? What cortical areas are necessary for perceptual decision-making? And finally, what neural mechanisms underlie the mapping of sensory percepts to appropriate motor outputs? We investigated the roles of visual (V1), posterior...

  9. Regulation of neuronal genomic integrity through histone deacetylase cooperativity

    Dobbin, Matthew Milnes
    While the mechanisms preserving genomic integrity are well defined in proliferating cells, corresponding pathways in postmitotic neurons remain poorly understood. In this report, I characterize the functions of two lysine deacetylases, SIRT1 and HDAC1, in the neuronal response to DNA double strand breaks (DSBs). Both SIRT1 and HDAC1 were previously shown to promote neuronal survival in a mouse model of neurodegeneration in which the appearance of DSBs precedes other neurotoxic symptoms. Here I show for the first time the recruitment of both SIRT1 and HDAC1 to sites of DNA DSBs in neurons, where they work cooperatively to coordinate DSB signaling...

  10. Gamma frequency entrainment attenuates amyloid load and modifies microglia

    Iaccarino, Hannah Frances
    Gamma oscillations (20-50 Hz), a common local field potential signature in many brain regions, are generated by a resonant circuit between fast-spiking (FS)-parvalbumin (PV)-interneurons and pyramidal cells. Changes in gamma oscillations have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies of these disorders is unclear. Here, we investigated this relationship using the 5XFAD mouse model of Alzheimer's disease (AD) and found reduced behaviorally driven gamma activity before the onset of plaque formation or evidence of cognitive decline. Because of the early onset of gamma deficits, we aimed to determine if exogenous gamma manipulations...

  11. The role of cortical layer six in the perception and laminar representation of sensory change

    Voigts, Jakob
    Neocortex learns predictive models of sensory input, allowing mammals to anticipate future events. A fundamental component of this process is the comparison between expected and actual sensory input, and the layered architecture of neocortex is presumably central to this computation. In this thesis, I examine the role of laminar differences, and specifically the role of layer 6 (L6) in the encoding and perception of stimuli that deviate from previous patterns. In awake mice, layer 4 neurons encode current stimulus deviations with a predominantly monotonic, faithful encoding, while neurons in layer 2/3 encode history dependent change signals with heterogeneous receptive fields....

  12. Targeting troubled translation : investigating novel therapeutic targets in mouse models of fragile X and 16p1 1.2 deletion syndrome

    Stoppel, Laura J. (Laura Jane)
    in 68 children born in the United States meets the diagnostic criteria for Autism Spectrum Disorder (ASD), a psychiatric illness that shares a high comorbidity with intellectual disability (ID). Despite the high prevalence of ASD, there are currently no mechanism-based treatments available due to a lack of understanding of the pathophysiological processes in the brain that disrupt behavior in affected individuals. Identifying convergent molecular pathways involved in known genetic causes of ASD and ID may broaden our understanding of these disorders and help advance potential targeted treatments for ASD. Synaptic protein synthesis is essential for modification of the brain through...

  13. An invariance-based account of feedforward categorization in a realistic model of the ventral visual pathway

    Mutch, James Vincent
    For the recognition of general objects in natural scenes, the current top-performing computer vision models owe a debt to visual neuroscience. The hierarchical architecture of convolutional networks, and related models such as HMAX, mimics that of the ventral stream of visual cortex. In essence, they apply the model of Hubel and Wiesel recursively, alternating layers of 'simple' cells, which are tuned to certain local features, and 'complex' cells, which pool the outputs of simple cells within a local region. With recent advances in deep learning, for many tasks in vision and speech, emphasis has moved away from so-called 'hand-designed' models...

  14. Converging roles of neurodevelopment and Wnt signaling in neuropsychiatric disorders

    Durak, Omer
    Neuropsychiatric Disorders are the leading category contributing to disability-adjusted life years (DALYs) in the U.S. according to the World Health Organization. These findings underline the vast burden caused by neuropsychiatric disorders on patients. However, effective treatments do not exist for many of the neuropsychiatric disorders mostly due to lack of understanding of disease pathology. Evidence from whole genome sequencing of psychiatric disorder patients increasingly suggest that Wnt signaling and cortical development - in addition to other perturbations - may underlie the pathophysiology of multiple disorders. Furthermore, besides autism spectrum disorder, contribution of neurodevelopmental dysregulations to disease etiology in late-onset disorder...

  15. At the interface of materials and objects in peripheral vision

    Keshvari, Shaiyan (Shaiyan Oliver)
    Humans are able to simultaneously perceive the world as discrete, distinct "objects", as well as regions of statistical regularity, or "textures". This is evident in the way we describe our perceptual world. A street is made up of concrete and asphalt "stuff", while the people and dogs walking on it are the "things" that make use of it. Both of these types of representation, however, are derived from the same sensory input, and thus there must exist transformations that map one to the other. A complete model of perception must account for these transformations. I study the representations that lie...

  16. Causal control of the thalamic reticular nucleus using optogenetic and novel chemogenetic approaches

    Higashikubo, Bryan T. (Bryan Takashi)
    Incoming sensory information from all modalities, with the exception of olfaction, synapses in the thalamus on the way to neocortex. This sensory relay is uniquely positioned to act as a gate, to determine which inputs from the periphery are processed by the neocortex. A key 'guardian' of the gate may be the thalamic reticular nucleus (TRN). The TRN is a primary source of GABAergic input to thalamic relay nuclei. The TRN projects directly to the rest of thalamus, generating feedforward and feedback inhibition. It is therefore positioned to mediate forebrain function, and specifically the computations of the neocortex-thalamic loop. Accordingly,...

  17. Human induced pluripotent stem cell models of Rett Syndrome reveal deficits in early cortical development

    Feldman, Danielle A. (Danielle Anagela)
    Rett Syndrome (RTT) is a pervasive, X-linked neurodevelopmental disorder that predominantly affects girls. The clinical patient features of RTT are most commonly reported to emerge between the ages of 6-18 months and as such, RTT has largely been considered to be a postnatal disorder. The vast majority of cases are caused by sporadic mutations in the gene encoding methyl CpG-binding protein 2 (MeCP2), which is expressed in the brain during prenatal neurogenesis and continuously throughout adulthood. MeCP2 is a pleiotropic gene that functions as a complex, high-level transcriptional modulator. It both regulates and is regulated by coding genes and non-coding...

  18. 4D mapping of network-specific pathological propagation in Alzheimer's disease

    Canter, Rebecca Gail
    Alzheimer's disease (AD) causes a devastating loss of memory and cognition for which there is no cure. Without effective treatments that slow or reverse the course of the disease, the rapidly aging population will require astronomical investment from society to care for the increasing numbers of AD patients. Additionally, the financial and emotional burden on families of affected individuals will be profound. Traditional approaches to the study of AD use either biochemical assays to probe cellular pathophysiology or non-invasive imaging platforms to investigate brain-wide network alterations. Though decades of research using these tools have advanced the field significantly, our increased...

  19. Control of intertemporal choice by dorsal raphe serotonergic neurons

    Xu, Sangyu
    While animals tend to prefer immediate rewards to delayed ones [1], delayed gratification is often advantageous [2]. Appropriate choice about future rewards is critical for survival. The dorsal raphe serotonergic neurons have been long implicated in the control of temporal discounting of reward [3] [4], but it is not clear whether their activities in fact direct the decision making process. In this thesis, I designed a cued intertemporal choice task for mice that allows the combination of highly specific genetic manipulations with sophisticated behavioral interrogations. The task utilizes odors to communicate upcoming reward contingencies to the mouse subjects. I found...

  20. The mechanisms of reliable coding in mouse visual cortex

    Rikhye, Rajeev V. (Rajeev Vijay)
    As we interact with the environment, our senses are constantly bombarded with information. Neurons in the visual cortex have to transform these complex inputs into robust and parsimonious neural codes that effectively guide behavior. The ability of neurons to efficiently convey information is, however, limited by intrinsic and shared variability. Despite this limitation, neurons in primary visual cortex (V1) are able to respond with high fidelity to relevant stimuli. My thesis proposes that high fidelity encoding can be achieved by dynamically increasing trial-to-trial response reliability. In particular, in this thesis, I use the mouse primary visual cortex (V1) as a...

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