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    Laser-Induced Apoptosis of Corticothalamic Neurons in Layer VI of Auditory Cortex Impact on Cortical Frequency Processing

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    Corticofugal projections outnumber subcortical input projections by far. However, the specific role for signal processing of corticofugal feedback is still less well understood in comparisonto the feedforward projection. Here, we lesioned corticothalamic (CT) neurons in layers V and/or VI of the auditory cortex of Mongolian gerbils by laser-induced photolysis to investigate their contribution to cortical activation patterns. We have used laminar current-source density (CSD) recordings of tone-evoked responses and could show that, particularly, lesion of CT neurons in layer VI affected cortical frequency processing. Specifically, we found a decreased gain of best-frequency input in thalamocortical (TC)-recipient input layers that correlated with the relative lesion of layer VI neurons, but not layer V neurons. Using cortical silencing with the GABA a -agonist muscimol and layer-specific intracortical microstimulation (ICMS), we found that direct activation of infragranular layers recruited a local recurrent cortico-thalamo-cortical loop of synaptic input. This recurrent feedback was also only interrupted when lesioning layer VI neurons, but not cells in layer V. Our study thereby shows distinct roles of these two types of CT neurons suggesting a particular impact of CT feedback from layer VI to affect the local feedforward frequency processing in auditory cortex

    Acute and Long-Term Circuit-Level Effects in the Auditory Cortex After Sound Trauma

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    Harmful environmental sounds are a prevailing source of chronic hearing impairments, including noise induced hearing loss, hyperacusis, or tinnitus. How these symptoms are related to pathophysiological damage to the sensory receptor epithelia and its effects along the auditory pathway, have been documented in numerous studies. An open question concerns the temporal evolution of maladaptive changes after damage and their manifestation in the balance of thalamocortical and corticocortical input to the auditory cortex (ACx). To address these issues, we investigated the loci of plastic reorganizations across the tonotopic axis of the auditory cortex of male Mongolian gerbils (Meriones unguiculatus) acutely after a sound trauma and after several weeks. We used a residual current-source density analysis to dissociate adaptations of intracolumnar input and horizontally relayed corticocortical input to synaptic populations across cortical layers in ACx. A pure tone-based sound trauma caused acute changes of subcortical inputs and corticocortical inputs at all tonotopic regions, particularly showing a broad reduction of tone-evoked inputs at tonotopic regions around the trauma frequency. At other cortical sites, the overall columnar activity acutely decreased, while relative contributions of lateral corticocortical inputs increased. After 4-6 weeks, cortical activity in response to the altered sensory inputs showed a general increase of local thalamocortical input reaching levels higher than before the trauma. Hence, our results suggest a detailed mechanism for overcompensation of altered frequency input in the auditory cortex that relies on a changing balance of thalamocortical and intracortical input and along the frequency gradient of the cortical tonotopic map

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    The adaptive primary auditory cortex microcircuitry across brain states, scales, and species

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    The planet, society, a human, their brain, and even the primary auditory cortex (A1) are complex systems. The A1 is built up by canonical microcircuits of neurons, that interact to allow us to adaptively hear, respond, and learn about our acoustic environment. The research detailed here, explored auditory response profiles and population activity in A1 across several physiological boundaries and this thesis seeks to contextualize findings in the framework of complexity. These boundaries were between awake and anesthetized wholistic brain states, across microscopic and mesoscopic scales, and between three small species. There is an expanding movement, beginning decades ago, to compliment scientific reductionism with context-informed study design and interpretation of results. Here, we looked at the interpretation of results for three projects first in a self-contained way, and then within a wider scope and in consideration of their place in the overall A1 complex system. The first project is about a critical shift in neuronal population activity after the application of ketamine-xylazine anesthesia. Ketamine, a common anesthetic, has been implicated, largely at a single or multi-unit level, in increased stimulus-locked excitability and inhibition of interneurons. We aimed to broaden understanding about the functional network mechanisms involved. I investigated the effects of an anesthetic dose of ketamine on Mongolian gerbil (Meriones unguiculatus) A1s after pure-tone stimulation using multichannel recordings across all cortical layers and subsequent analysis of the current-source density (CSD) profiles. Overall, we found a significant gain increase in granular input layers under ketamine. We ruled out a cross-trial coherence differences at the time of stimulus onset and could instead provide evidence for a granular layer broadband increase in magnitude, reflecting a stimulus-locked increase in recurrent excitation. Our findings on a population level supported the common hypothesis of cortical disinhibition via suppression of GABAergic interneurons. The second project shows the suppression of population activity after a transient Cav2.1 voltage gated calcium channel (VGCC) clustering using a modern state-of-the-art optogenetic aggregation technique. The stochastic dynamics of each cell involved in population activity is dependent on the position of highly mobile, pre-synaptic VGCCs. When VGCCs were clustered in their respective active zones in vitro, it caused a more deterministic firing response profile per cell. To investigate the effects of reducing variability at a single cell level on a population in vivo, we used a new optogenetic tool to cross-link VGCCs via a photo-cross-linkable cryptochrome mutant, CRY2olig, in transgenic mice (Mus musculus). We found that clustering VGCCs suppressed cortical population activity dynamically, with greater suppression during sensory-evoked activity and greater still given highly synchronized distribution of synaptic inputs. Our results reveal that the mobility of VGCCs, which introduce variability into the network, is an important feature of sensory encoding via dynamic adjustment of activity across differing synaptic input strengths. The third project explores the impact of the ecological niche of an organism on the organization and function of the A1. Therefore, we investigated laminar auditory response profiles of seba’s short-tailed bats (Carollia perspicillata) and mice. Bats are a veritable auditory specialist, given their evolution to navigate 3-dimensionally with echolocation and sophisticated social communication, while mice are more specialized in other sensory systems. We investigated the differential recruitment of their respective A1 microcircuitry to auditory stimuli at set repetition rates. We generally found that mice had higher intrinsic background noise and that bats had a better signal to noise ratio, leading to a more temporally precise and lower-energy-cost cortical representation of consecutive stimuli. Despite methodological considerations, the phase coherence in bats was significantly higher across all oscillatory frequencies, indicating less inter-trial phase variability. These results indicate a possible loss of flexibility as a trade-off for higher temporal precision due to this specialization or hint at species-specific mechanisms to assist in dynamic adaptation. Altogether, these studies are tackling fundamentally different topics through the exploration of A1 population activity in three small mammalian species. The balance of excitation and inhibition, introduction of variability, and differential recruitment for specialization underlie the successfully robust and adaptive A1—an integral complex system for our ability to perceive and interact meaningfully with the world we live in.Der primäre auditorische Kortex (A1), das Gehirn, der Mensch, die Gesellschaft und der Planet sind komplexe Systeme. Die hier vorgestellten Forschungsarbeiten untersuchen auditorische Antwortcharakteristika von Nervenzell-Populationen über mehrere physiologische Grenzen hinweg. Ziel der vorliegenden Arbeit ist es, die Ergebnisse von drei separaten Studien im Kontext der Komplexität zusammen zu führen. Diese Studien thematisieren wache und narkotisierte Gehirnzustände, mikroskopische und mesoskopische Messbereiche und die Unterschiede der neuronalen Organisation des A1 zwischen drei Spezies. Seit Jahrzehnten gibt es eine wachsende Bewegung, den wissenschaftlichen Reduktionismus durch kontextbezogene Studiengestaltung und Interpretation der Ergebnisse zu ergänzen. In dieser Arbeit werden die Ergebnisse dreier Projekte vorgestellt, zunächst in einem eigenständigen Rahmen, um sie dann in einem größeren Zusammenhang und unter Berücksichtigung ihrer Stellung im komplexen Gesamtsystem A1 zu vergleichen. Das erste Projekt befasst sich mit dem Einfluss einer Ketamin-Xylazin-Narkose auf die Aktivität neuronaler Populationen. Ketamin, ein gebräuchliches Anästhetikum, wird vor allem auf der Ebene einzelner oder mehrerer Einheiten mit einer erhöhten stimulusgebundenen Erregbarkeit und Hemmung von Interneuronen in Verbindung gebracht. Unser Ziel war es, das Verständnis auf der Ebene der beteiligten funktionellen Netzwerkmechanismen zu erweitern. Wir untersuchen die Auswirkungen einer anästhetischen Dosis Ketamin auf die Neuronen im A1 der Mongolischen Wüstenrennmaus (Meriones unguiculatus) nach Stimulation mit Reintönen mittels Multikanal-Ableitungen über alle kortikalen Schichten und nachfolgender Analyse der Strom-Quellen-Dichte-Verteilung. Insgesamt fanden wir unter Ketamin einen signifikanten Anstieg der Verstärkung in den granulären Eingangs-Schichten. Wir schlossen Kohärenzunterschiede über Messwiederholungen zum Zeitpunkt des Stimulusbeginns als Erklärung aus und konnten stattdessen zeigen, dass die Befunde durch eine stimulusabhängige Rekrutierung rekurrenter Schaltkreise erklärt wird. Unsere Ergebnisse auf Populationsebene unterstützen damit die gängige Hypothese der kortikalen Enthemmung durch Unterdrückung von GABAergen Interneuronen. Das zweite Projekt zeigt die Unterdrückung der Populationsaktivität nach einer Aggregation von presynaptischen Cav2.1 spannungsgesteuerten Kalziumkanälen (VGCC) mittels modernster state-of-the-art Optogenetik-Technik. Die stochastische Dynamik jeder Zelle, die an der Populationsaktivität beteiligt ist, hängt von der Position der mobilen, präsynaptischen VGCCs ab. Wenn VGCCs in ihren jeweiligen aktiven Zonen in vitro geclustert wurden, führte dies zu einem deterministischeren Antwortprofil der Zelle. Um die Auswirkungen der Verringerung der Variabilität auf der Ebene einer einzelnen Zelle auf Populationsebene in vivo zu untersuchen, verwenden wir ein neues optogenetisches Werkzeug zur Vernetzung von VGCCs über eine photovernetzbare Cryptochrom-Mutante, CRY2olig, in transgenen Mäusen (Mus musculus). Die transiente Aggregation von VGCCs unterdrückt die Aktivität der kortikalen Population bei sensorisch evozierter Aktivität, je synchronisierter die synaptischen Eingänge, desto größer der Effekt. Unsere Ergebnisse zeigen, dass die Mobilität der VGCCs die Variabilität auf Netzwerk-Ebene ermöglicht und somit ein wichtiges Merkmal der sensorischen Kodierung durch dynamische Anpassung der Aktivität bei unterschiedlichen synaptischen Eingangsstärken darstellt. Das dritte Projekt erforscht die Auswirkungen der ökologischen Nische eines Organismus auf die Organisation und Funktion des A1. Zu diesem Zweck haben wir die laminaren Antwortprofile von Seba-Kurzschwanzfledermäusen (Carollia perspicillata) und Mäusen verglichen. Fledermäuse sind wahre Hörspezialisten, da sie sich evolutionär entwickelt haben, um mit Hilfe der Echoortung dreidimensional zu navigieren und eine ausgefeilte soziale Kommunikation zu betreiben, während Mäuse eher auf andere Sinnessysteme spezialisiert sind. Wir untersuchen die unterschiedliche Rekrutierung ihrer jeweiligen A1-Mikroschaltkreise auf auditorische Reize bei bestimmten Wiederholungsraten. Im Allgemeinen konnten wir zeigen, dass Mäuse ein höheres intrinsisches Hintergrundrauschen und Fledermäuse ein besseres Signal-Rausch-Verhältnis aufweisen, was zu einer zeitlich präziseren und weniger energieaufwändigen kortikalen Repräsentation aufeinander folgender Reize führt. Die Phasenkohärenz war bei Fledermäusen über alle Schwingungsfrequenzen hinweg signifikant höher, was auf eine geringere Phasenvariabilität zwischen den Versuchen hindeutet. Diese Ergebnisse deuten auf einen möglichen Verlust an Flexibilität als Kompromiss für eine höhere zeitliche Präzision aufgrund dieser Spezialisierung hin oder geben Hinweise auf spezies-spezifische Mechanismen zur Unterstützung der dynamischen Anpassung. Insgesamt befassen sich diese Studien mit grundlegend unterschiedlichen Themen durch die Erforschung der Aktivität der A1-Population bei drei kleinen Säugetierarten. Das Gleichgewicht zwischen Erregung und Hemmung, die Einführung von Variabilität und die unterschiedliche Rekrutierung für die Spezialisierung bilden die Grundlage für ein erfolgreiches, robustes und anpassungsfähiges System des Hörkortex A1 - ein integrales komplexes System für unsere Fähigkeit, die Welt, in der wir leben, wahrzunehmen und sinnvoll mit ihr zu interagieren

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

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    Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits

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    The primary auditory cortex (A1) is an essential node in the integrative brain network that encodes the behavioral relevance of acoustic stimuli, predictions, and auditory-guided decision making. Previous studies have revealed task-related information being present at both the single-unit and population activity. However, its realization with respect to the cortical microcircuitry is less well understood. In this study, we used chronic, laminar current source density (CSD) analysis from the A1 of behaving Mongolian Gerbils (Meriones unguiculatus) in order to characterize layer-specific, spatiotemporal synaptic population activity. Animals were trained to first detect and subsequently to discriminate two pure tone frequencies in consecutive training phases in a Go/NoGo shuttle-box task. We demonstrate that not only sensory but also task- and choice-related information is represented in the mesoscopic neuronal population code distributed across cortical layers. Based on a single-trial analysis using generalized linear-mixed effect models (GLMM), we found infragranular layers to be involved in auditory-guided action initiation during tone detection. Supragranular layers, particularly, are involved in the coding of choice options during tone discrimination. Further, we found that the overall columnar synaptic network activity represents the accuracy of the opted choice. Moreover, cognitive flexibility was represented in the A1 during multiple reversal of choice-outcome contingency task. During those cognitive processes, the infragranular layer VI continuously updates the network in order to optimize of the discrimination performance, while the supragranular layers promote the choice accuracy, especially at states with higher task-engagement and performance. Our study thereby suggests a multiplexed cortical representation of stimulus features in dependence of the task, action selection, and the behavioral options of the animal in preparation of correct choices. The findings expand our understanding of how individual layers contribute to the integrative circuit of the A1 in order to code task-relevant information and guide sensory-based decision making
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