47 research outputs found

    Spiking neural network connectivity and its potential for temporal sensory processing and variable binding

    Get PDF
    Copyright © 2013 Wall and Glackin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these termsPeer reviewedFinal Published versio

    Neurosystems: brain rhythms and cognitive processing

    Get PDF
    Neuronal rhythms are ubiquitous features of brain dynamics, and are highly correlated with cognitive processing. However, the relationship between the physiological mechanisms producing these rhythms and the functions associated with the rhythms remains mysterious. This article investigates the contributions of rhythms to basic cognitive computations (such as filtering signals by coherence and/or frequency) and to major cognitive functions (such as attention and multi-modal coordination). We offer support to the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations.098352 - Wellcome Trust; 5R01NS067199 - NINDS NIH HH

    Neural gain control measured through cortical gamma oscillations is associated with sensory sensitivity

    Get PDF
    Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations. Recent studies in humans and nonhuman primates have shown that strong excitatory drive to the visual cortex leads to suppression of induced gamma oscillations, which may reflect inhibitory-based gain control of network excitation. The efficiency of the gain control measured through gamma oscillations may in turn affect sensory sensitivity in everyday life. To test this prediction, we assessed the link between self-reported sensitivity and changes in magneto-encephalographic gamma oscillations as a function of motion velocity of high-contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally elevated sensory sensitivity. We conclude that intensity-related suppression of gamma response is a promising biomarker of homeostatic control of the excitation-inhibition balance in the visual cortex

    Within-Host Evolution Of Hiv-1: Novel Pathways Of Virus Escape From Cellular And Humoral Immunity

    Get PDF
    Longitudinal HIV-1 single genome sequencing (SGS), which permits unambiguous genetic characterization of circulating viral strains without introduction of PCR error, can be used to identify sites in the viral genome that are under selective pressure. Following transmission, the earliest sites under positive selection often fall in cytotoxic T lymphocyte (CTL) epitopes. During escape from CTL immune pressure, viral sequences typically exhibit nonsynonymous mutations within the span of the cognate T cell epitope. I applied SGS to study sequence evolution in the HIV-1 5’ leader sequence, which is thought to be translationally silent. I observed mutational patterns consistent with CTL escape and demonstrated that the HIV-1 5’ leader expresses T cell antigens from non-canonical one-off AUG codons (e.g. CUG). While these non-canonical start codons can be mutated during CTL escape, a reverse transcriptase overextension error periodically restores a one-off AUG within the 5’ leader. As infection ensues, sites under selection within the gene encoding the viral envelope glycoprotein (Env) often fall within autologous neutralizing antibody epitopes. In a subset of individuals, the strain-specific neutralizing antibody response develops into a broadly cross-reactive neutralizing antibody (bnAb) response. To understand what factors influence bnAb ontogeny, I used SGS to study Env evolution both during natural infection and immunotherapy. I found viral diversification in bnAb contact residues and divergence of the virus population into multiple persistent lineages to precede bnAb development. Taken together, these data demonstrate that longitudinal HIV-1 SGS can be used to discover novel aspects of virus biology and host-pathogen interactions

    Interacting Mechanisms Driving Synchrony in Neural Networks with Inhibitory Interneurons

    Full text link
    Computational neuroscience contributes to our understanding of the brain by applying techniques from fields including mathematics, physics, and computer science to neuroscientific problems that are not amenable to purely biologic study. One area in which this interdisciplinary research is particularly valuable is the proposal and analysis of mechanisms underlying neural network behaviors. Neural synchrony, especially when driven by inhibitory interneurons, is a behavior of particular importance considering this behavior play a role in neural oscillations underlying important brain functions such as memory formation and attention. Typically, these oscillations arise from synchronous firing of a neural population, and thus the study of neural oscillations and neural synchrony are deeply intertwined. Such network behaviors are particularly amenable to computational analysis given the variety of mathematical techniques that are of use in this field. Inhibitory interneurons are thought to drive synchrony in ways described by two computational mechanisms: Interneuron Network Gamma (ING), which describes how an inhibitory network synchronizes itself; and Pyramidal Interneuron Network Gamma (PING), which describes how a population of interneurons inter-connected with a population of excitatory pyramidal cells (an E-I network) synchronizes both populations. As first articulated using simplified interneuron models, these mechanisms find network properties are the primary impetus for synchrony. However, as neurobiologists uncover interneurons exhibiting a vast array of cellular and intra-connectivity properties, our understanding of how interneurons drive oscillations must account for this diversity. This necessitates an investigation of how changing interneuron properties might disrupt the predictions of ING and PING, and whether other mechanisms might interact with or disrupt these network-driven mechanisms. In my dissertation, I broach this topic utilizing the Type I and Type II neuron classifications, which refer to properties derived from the mathematics of coupled oscillators. Classic ING and PING literature typically utilize Type I neurons which always respond to an excitatory perturbation with an advance of the subsequent action potential. However, many interneurons exhibit Type II properties, which respond to some excitatory perturbations with a delay in the subsequent action potential. Interneuronal diversity is also reflected in the strength and density of the synaptic connections between these neurons, which is also explored in this work. My research reveals a variety of ways in which interneuronal diversity alters synchronous oscillations in networks containing inhibitory interneurons and the mechanisms likely driving these dynamics. For example, oscillations in networks of Type II interneurons violate ING predictions and can be explained mechanistically primarily utilizing cellular properties. Additionally, varying the type of both excitatory and inhibitory cells in E-I networks reveals that synchronous excitatory activity arises with different network connectivities for different neuron types, sometimes driven by cellular properties rather than PING. Furthermore, E-I networks respond differently to varied strengths of inhibitory intra-connectivity depending upon interneuron type, sometimes in ways not fully accounted for by PING theory. Taken together, this research reveals that network-driven and cellularly-driven mechanisms promoting oscillatory activity in networks containing inhibitory interneurons interact, and oftentimes compete, in order to dictate the overall network dynamics. These dynamics are more complex than those predicted by the classic ING and PING mechanisms alone. The diverse dynamical properties imparted to oscillating neural networks by changing inhibitory interneuron properties provides some insight into the biological need for such variability.PHDApplied and Interdisciplinary MathematicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143981/1/sbrich_1.pd

    Electronic systems for intelligent particle tracking in the High Energy Physics field

    Get PDF
    This Ph.D thesis describes the development of a novel readout ASIC for hybrid pixel detector with intelligent particle tracking capabilities in High Energy Physics (HEP) application, called Macro Pixel ASIC (MPA). The concept of intelligent tracking is introduced for the upgrade of the particle tracking system of the Compact Muon Solenoid (CMS) experiment of the Large Hadron Collider (LHC) at CERN: this detector must be capable of selecting at front--end level the interesting particle and of providing them continuously to the back-end. This new functionality is required to cope with the improved performances of the LHC when, in about ten years' time, a major upgrade will lead to the High Luminosity scenario (HL-LHC). The high complexity of the digital logic for particle selection and the very low power requirement of 95% in particle selection and a data reduction from 200 Tb/s/cm2 to 1 Tb/s/cm2. A prototype, called MPA-Light, has been designed, produced and tested. According to the measurements, the prototype respects all the specications. The same device has been used for multi-chip assembly with a pixelated sensor. The assembly characterization with radioactive sources conrms the result obtained on the bare chip

    Structural and Functional Characterization of Non-Homologous End Joining Factors

    Get PDF
    DNA double strand breaks represent the most toxic form of DNA damage. In mammals, non-homologous end-joining (NHEJ) is the primary DNA repair pathway for such damage, preventing both carcinogenesis and accelerated aging. Structural understanding of this repair pathway has received considerable attention, but has been significantly limited by the inability to obtain structures of higher order nucleoprotein complexes. A main obstacle in this respect has been difficulty in obtaining highly purified proteins, sufficient for structural determination. Improved protein expression and purification methods developed in this thesis permitted several NHEJ complexes to be selected for structural studies. Among these, Ku70-DNA and Ku70-DNA-PAXX yielded promising preliminary results. In depth optimization for crystal growth was performed and resulted in a full-length PAXX homodimer structure as well as low-resolution diffraction data for a novel Ku70-DNA complex. The PAXX structure confirmed prior suggestions that the C-terminal region of PAXX is highly disordered

    The role of early cytotoxic lymphocyte (CTL) escape in the pathogenesis of HIV-1 subtype C infection

    Get PDF
    Includes abstract.Includes bibliographical references.This study investigated the frequency and timing of cytotoxic T-lympthocyte (CTL) escape and its pathogenic consequences on HIV-1 subtype C disease progression

    The 1992 Shuttle Small Payloads Symposium

    Get PDF
    The 1992 Shuttle Small Payloads Symposium is a continuation of the Get Away Special Symposium convened from 1984 through 1988, and is proposed to continue as an annual conference. The focus of this conference is to educate potential Space Shuttle Payload Bay users as to the types of carrier systems provided and for current users to share experiment concepts
    corecore