Representation of acoustic deviations by neurons and local fieldpotentials in the auditory cortex of the awake rat

Veränderungen in der akustischen Umwelt sind häufig mit Ereignissen verbunden. Diese wiederum können für ein Tier eine besondere Verhaltensrelevanz haben, im Gegensatz zu einem gleichbleibenden akustischen Hintergrund, der mit keinem positiven oder negativen Ereignis verbunden ist. Es ist also naheliegend zu spekulieren, dass Veränderungen oder neue akustische Reize im zentralen Nervensystem anders repräsentiert werden als der kontinuierliche Hintergrund und dass diese Repräsentation sowohl von der Häufigkeit der Stimuli als auch vom Unterschied zum akustischen Hintergrund abhängt. In Elektroenzaphalografie-Messungen (EEG) am Menschen wurde eine besondere Aktivitätsänderung bei auditorischen Abweichungen erstmals 1978 nachgewiesen. Dabei wurde ein akustischer Reiz über einen längeren Zeitraum regelmäßig wiederholt (Standard) und in einigen, seltenen Fällen durch einen anderen Reiz (Deviant) ersetzt. Dieser Deviant löste eine zusätzliche negative Komponente im EEG aus (Mismatch negativity), die bei den Standard-Stimuli nicht vorhanden war. Eine Voraussetzung, um MMN auszulösen, ist die Präsentation von einigen Standard-Stimuli, sodass eine neuronale Repräsentation des Stimulus aufgebaut werden kann, gegen die jeder weitere Reiz abgeglichen wird. Die zelluläre Basis von MMN und des zugrunde liegenden Mechanismus zur Detektion von auditorischen Veränderungen ist nur wenig erforscht. Als möglicher zellulärer Detektionsmechanismus akustischer Veränderungen wurde die Stimulus-spezifische Adaptation (SSA) vorgeschlagen, die zugleich der Ursprung von MMN im primären auditorischen Kortex sein könnte. SSA beschreibt die Eigenschaft von Neuronen der Hörbahn, auf die Wiederholung von identischen Reizen mit abnehmender Aktivität zu antworten und zugleich die Fähigkeit beizubehalten, andere Stimuli weiterhin mit hoher Aktivität zu repräsentieren. Die veränderte neuronale Repräsentation von Tönen mit niedriger Auftrittswahrscheinlichkeit, im Vergleich zu Tönen mit hoher Auftrittswahrscheinlichkeit, wurde bereits sehr eindrücklich im auditorischen Kortex der anästhesierten Katzen demonstriert. Die vorliegende Arbeit hat es sich zum Ziel gesetzt, bei der Repräsentation von auditorischen Abweichungen die Lücke zwischen der Ebene aufsummierter Potenziale (EEG beim Menschen) und der Ebene einzelner kortikaler Neurone zu schließen. Gleichzeitig sollte dabei erstmalig SSA im auditorischen Kortex des wachen Tieres nachgewiesen und so eine pharmakologische Interaktion der normalerweise eingesetzten Anästhetika mit SSA ausgeschlossen werden. Der experimentelle Ansatz basierte auf elektrophysiologischen Messungen mit chronisch implantierten Mikroelektroden im wachen Tier. Die Elektroden waren im auditorischen Kortex positioniert und ermöglichten eine gleichzeitige Messung der lokalen aufsummierten Potenziale (lokale Feldpotenziale, LFP) und der Aktionspotenziale einzelner Neurone als extrazelluläre Potenzialveränderungen. Das Stimulationsparadigma bestand aus Folgen zweier Reintöne, die mit unterschiedlicher Auftrittwahrscheinlichkeit präsentiert wurden. Der Ton mit hoher Auftrittwahrscheinlichkeit bildete den akustischen Hintergrund, der Ton mit niedriger Auftrittswahrscheinlichkeit (Deviant) die akustische Abweichung. In dieser Arbeit konnte erstmalig nachgewiesen werden, dass Neurone im auditorischen Kortex der wachen Ratte akustische Abweichungen mit einer höheren Aktivität repräsentieren als den auditorischen Hintergrund (bis zu 19,5% Aktivitätsunterschied). Stimulusspezifische Adaptation ist somit auch im wachen Tier Teil der neuronalen Codierung der akustischen Umwelt. Mithilfe der Signalentdeckungstheorie konnte des Weiteren gezeigt werden, dass die unterschiedliche neuronale Repräsentation von häufigen und seltenen Stimuli auch zu einer erhöhten neuronalen Unterscheidbarkeit zwischen beiden Stimuli führte. Auf der Ebene der ereigniskorrelierten LFPs konnte SSA in zwei Komponenten nachgewiesen werden: der ersten, negativen Auslenkung und der folgenden, positiven Auslenkung. Besonders in der ersten, negativen Komponente war SSA systematisch nachzuweisen und sie war zusätzlich starkmit der Aktivität der einzelnen Neuronen korreliert, während die positive Komponente der LFPs keine Korrelation mit den Messungen der einzelnen Nervenzellen zeigte. Der Grad der SSA hing von der Auftrittwahrscheinlichkeit und dem Frequenzabstand der beiden Töne ab. Keine der Messungen hatte die besondere Charakteristik von MMN. Zusammenfassend lässt sich die Aussage treffen, dass SSA auch im wachen Tier nachgewiesen wurde, sowohl auf der Ebene einzelner Neurone als auch in der aufsummierten Aktivität, wenn auch in einer schwächeren Ausprägung als in den bisher veröffentlichten Ergebnissen in anästhesierten Tieren. Ein direkter Beitrag der kortikalen Neurone zu MMN konnte nicht gezeigt werden, es gab aber einen starken Zusammenhang zwischen den einzelnen Neuronen und den LFPs.The representation of behaviorally relevant stimuli in a noisy and complex environment that consists of multiple signals from different sources is one of the major challenges for the auditory system. The statistics of stimuli provide critical cues for structuring such an environment for optimizing the neuronal coding of it and for selecting vital information from it. In this respect, infrequent deviations in a repetitive auditory background are often events of behavioral importance. Such rarely occurring events are represented in the nervous system by a preattentive and automatic auditory process, which is only partially under attentional control. A correlate in human electroencephalographic recordings for neuronal mechanisms of change detection is the so-called mismatch negativity (MMN) that may serve as a trigger for reallocating attention toward the deviants. Its characteristic feature is a negative wave occurring 200 milliseconds after stimulus onset in response to an infrequent deviant stimulus, which is embedded in a sequence of repetitive standard tones. To evoke MMN, the deviant and standard stimuli can be selected from a variety of stimuli (i.e., pure tones, vowels) and differ in various aspects such as frequency, duration, and level or even being omitted. Although there is a large data basis on MMN available, only few publications approach its cellular basis in terms of cortical neuronal response properties. Recently, stimulus-specific adaptation has been proposed as a candidate neuronal mechanism underlying the generation of MMN. In experiments on anesthetized animals, stimulus-specific adaptation was identified at different stages of the auditory pathway, namely cat auditory cortex, mouse auditory thalamus, and rat inferior colliculus. In addition, there were attempts to demonstrate MMN with means of event-related potentials in rodents, but the resulting patterns are weak or ambiguous. To address the neuronal basis of MMN, the present study focuses on the awake rat primary auditory cortex. Neurons and evoked local field potentials were recorded in parallel and could provide a bridge between cellular properties and electroencephalographic recordings. The following questions are addressed. Whether and how is SSA present in neurons of the primary auditory cortex in the awake rat? Do the evoked local field potentials adapt in a similar manner as neurons and do they exhibit an MMN-like pattern? Finally, can we establish a contribution of single neuron adaptation to adaptation of evoked local field potentials? A total of 76 single units and small multiunit clusters were recorded (n = 27 and n = 49, respectively) from primary auditory cortex of the awake rat. For a subset of units, evoked local field potentials were recorded in parallel to the extracellular spike recordings from the same electrode. The frequency response area was characterized for each unit, and, depending on its characteristic frequency, two frequencies, symmetrically centered around the characteristic frequency, were chosen for the two tones in the adaptation paradigm. The two pure tones were presented in an oddball sequence of 800 tones, with one tone being the highly probable standard and the other one the rarely occurring deviant. In a second consecutive sequence, the frequencies of standard and deviant were swapped. To identify different factors controlling stimulus-specific adaptation, deviant probability and frequency separation were varied systematically, giving rise to four different stimulus conditions and one control condition. The main findings were as follows. (1) Isolated units in primary auditory cortex of the awake rat showed stimulus-specific adaptation primarily during the onset response but could not be observed during later inhibition or rebound of activity. Stimulus-specific adaptation of isolated units depended on at least two factors: frequency separation between standard tone and deviant and the deviant probability. However, stimulus-specific adaptation was independent of the specific frequency, indicating that stimulus-specific adaptation might be a more general property of cortical neurons. (2) Certain components of evoked local field potentials adapted in a stimulus-specific manner (i.e., the fast negative deflection and partially the slower positive deflection). There was, however, no MMN response present. (3) Spike adaptation correlated well with the adaptation of the negative deflection but not the positive deflection. Adaptation of the negative deflection resembled spike adaptation with respect to magnitude and dependency on frequency separation and deviant probability. (4) Stimulus specific adaptation improves on the level of single neurons the discriminability of deviant stimuli from the acoustic background. This was shown by a detailed analysis of neuronal responses with means of signal detection theory

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Machine learning reveals interhemispheric somatosensory coherence as indicator of anesthetic depth

The goal of this study was to identify features in mouse electrocorticogram recordings that indicate the depth of anesthesia as approximated by the administered anesthetic dosage. Anesthetic depth in laboratory animals must be precisely monitored and controlled. However, for the most common lab species (mice) few indicators useful for monitoring anesthetic depth have been established. We used electrocorticogram recordings in mice, coupled with peripheral stimulation, in order to identify features of brain activity modulated by isoflurane anesthesia and explored their usefulness in monitoring anesthetic depth through machine learning techniques. Using a gradient boosting regressor framework we identified interhemispheric somatosensory coherence as the most informative and reliable electrocorticogram feature for determining anesthetic depth, yielding good generalization and performance over many subjects. Knowing that interhemispheric somatosensory coherence indicates the effectively administered isoflurane concentration is an important step for establishing better anesthetic monitoring protocols and closed-loop systems for animal surgeries

Deep-learning-based identification, tracking, pose estimation and behaviour classification of interacting primates and mice in complex environments

The quantification of behaviors of interest from video data is commonly used to study brain function, the effects of pharmacological interventions, and genetic alterations. Existing approaches lack the capability to analyze the behavior of groups of animals in complex environments. We present a novel deep learning architecture for classifying individual and social animal behavior, even in complex environments directly from raw video frames, while requiring no intervention after initial human supervision. Our behavioral classifier is embedded in a pipeline (SIPEC) that performs segmentation, identification, pose-estimation, and classification of complex behavior, outperforming the state of the art. SIPEC successfully recognizes multiple behaviors of freely moving individual mice as well as socially interacting non-human primates in 3D, using data only from simple mono-vision cameras in home-cage setups

Pacifism in Fin-de-Siècle Austria: The Politics and Limits of Peace Activism

The late Habsburg Monarchy produced two of the most renowned peace activists of their day: Bertha von Suttner and Alfred Fried. In comparison to these two Nobel Peace laureates, the main association of Austro-pacifism – the Österreichische Friedensgesellschaft (ÖFG) – is less well known. The article concentrates on this organization, which had been founded in 1891, and it draws attention to the political and intellectual environment in which it operated. The ÖFG originated in the milieu of Austro-German liberalism, but had an ambivalent rapport with liberal politics. The Austro-pacifists' focus on supranational principles and dynastic loyalty sat uneasily with the national dimensions of Cisleithanian politics. The obstacles encountered by the ÖFG illustrate wider aspects of the political culture of fin-de-siècle Austria, ranging from the question of militarism in Austrian society to the challenges created by socialist and nationalist movements. As a whole, the article highlights the inherent limitations of Austro-pacifism, as reflected in its quest for respectability and its acceptance of the social and political order

AMERICA. Mapas generales (1879). 1:3831414

Coordenadas referidas al meridiano de Hierro y de París (O 180 -E 40 /N 70 48'-S 50 36')Relieve representado por normalesIndica la leyenda de los signos utilizado

Spatially heterogeneous argon-isotope systematics and apparent ⁴⁰Ar/³⁹Ar ages in perlitised obsidian

In situ laser ablation Ar-isotope analyses of variably hydrated and devitrified obsidian from the ~ 27 Ma Cochetopa Dome, San Juan, USA, reveal complex interplay between degassing of initial Ar and absorption of atmospheric Ar. These processes have locally modified the Ar-isotope composition of the obsidian and led to spurious, spatially-heterogeneous Ar-isotope and 40Ar/39Ar age data. Small perlite beads exhibit older apparent Ar-ages at the rims than the cores. This is interpreted as an apparent excess of 40Ar at the rims, produced either by a) diffusion of excess 40Ar into the bead during flushing of the lava with excess 40Ar-bearing volcanic gas, or by b) isotopic fractionation during degassing of initial Ar, causing preferential loss of 36Ar over 40Ar at the bead rims. The second interpretation is favoured by a relative enrichment of 36Ar in the core of a perlite bead along a microlite-free (poorly degassed) flow band, and by a lack of age variation in a larger, fresh, well-degassed perlite bead. These isotopic gradients were later overprinted during glass hydration by absorption of Ar with near-atmospheric composition, resulting in elevated 36Ar and reduced radiogenic 40Ar* yields at the rims of perlite beads. These complex interactions essentially represent the mixing of three distinct Ar reservoirs: initial trapped Ar that may or may not be fractionated, an isotopically atmospheric Ar component introduced during hydration, and radiogenic 40Ar*. Such reservoir mixing is the underlying reason for poor correlations on isotope correlation diagrams and the difficulties in validating the composition of the non-radiogenic Ar component. We thus suggest that high 36Ar yields are a combination of the incomplete degassing of initial (possibly magmatic) Ar and the gain of Ar during interaction between the obsidian and meteoric/atmospheric fluids. Our analyses emphasise the challenging nature of 40Ar/39Ar dating obsidian samples, but also point to possible solutions by careful sample characterisation and selection of highly degassed samples

ErbB4 regulates the timely progression of late fetal lung development

AbstractThe ErbB4 receptor has an important function in fetal lung maturation. Deletion of ErbB4 leads to alveolar hypoplasia and hyperreactive airways similar to the changes in bronchopulmonary dysplasia (BPD). BPD is a chronic pulmonary disorder affecting premature infants as a consequence of lung immaturity, lung damage, and abnormal repair. We hypothesized that proper ErbB4 function is needed for the timely progression of fetal lung development. An ErbB4 transgenic cardiac rescue mouse model was used to study the effect of ErbB4 deletion on fetal lung structure, surfactant protein (SP) expression, and synthesis, and inflammation. Morphometric analyses revealed a delayed structural development with a significant decrease in saccular size at E18 and more pronounced changes at E17, keeping these lungs in the canalicular stage. SP-B mRNA expression was significantly down regulated at E17 with a subsequent decrease in SP-B protein expression at E18. SP-D protein expression was significantly decreased at E18. Surfactant phospholipid synthesis was significantly decreased on both days, and secretion was down regulated at E18. We conclude that pulmonary ErbB4 deletion results in a structural and functional delay in fetal lung development, indicating a crucial regulatory role of ErbB4 in the timely progression of fetal lung development