Wir danken allen Labormitgliedern für ihren Beitrag zum Schreiben und sorgfältigen Lesen dieses Manuskripts. Wir danken Paul Franken für die Anregung von Diskussionen, Dr. Gisèle Ferrand für hilfreiche Kommentare zum chirurgischen Protokoll und Dr. Jean-Yves Chatton für die Bereitstellung der Original Labview ausführbaren Dateien für die Lärmbelastung. Die Finanzierung erfolgte durch den Schweizerischen Nationalfonds (Stipendien 31003A_146244 und 31003A_166318) und den Etat de Vaud.

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Die Autoren erklären, dass sie keine konkurrierenden finanziellen Interessen haben.

Hier zeigen wir, wie ein kontinuierliches zeitliches Profil des Nicht-REM-Schlafes aufgebaut wird, der EEG-, EMG- und EKG-Variablen integriert. Dies ist ein erster Schritt zur Entwicklung einer integrativen Beschreibung des Mausschlafes, die dazu beitragen kann, die bisher nicht erkannte Zeitskala zu identifizieren, über die bei Nicht-REM-Schlaf 1 hohe und geringe Geräuscharmität organisiert wird. Eine ähnliche zeitliche Struktur wurde auch im menschlichen Nicht-REM-Schlaf durch eine analoge ...

Säugetier-Schlaf ist ein Verhaltenszustand der Ruhe und der Resilienz gegenüber Umweltreizen. Trotz dieser scheinbaren Homogenität, Polysomnographie und vegetative Parameter zeigen , dass die Schlaf bewegt sich zwischen qualitativ und quantitativ unterschiedliche neuronale und somatische Zustände auf verschiedenen räumlichen und zeitlichen Skalen 1. Über Minuten bis zu zehn Minuten tritt der Wechsel zwischen Nicht-REM und REM-Schlaf auf. Nicht-REM-Schlaf wird von einer großampligen, niederfrequenten Aktivität im EEG mit einem spektralen Peak um ~ 0,5 - 4 Hz begleitet, während REM-Schlaf eine regelmäßige EEG-Aktivität im Theta-Band (6 - 10 Hz) aufweist Muskel atonia 2 Innerhalb des Nicht-REM-Schlafes radeln die Menschen durch Licht (S2) und tiefen Langsamwellen-Schlaf (SWS). Wie ihre Benennung zeigt, zeigen diese beiden Stufen niedrigere und höhere Erregungsschwellen 3 , 4 , und sie unterscheiden sich primär in der Dichte von NiedrighäutenEn-kortikale EEG-Leistung, die als langsame Aktivität (SWA; 0,75 - 4 Hz) bezeichnet wird. Die Ungleichförmigkeit bleibt während der einzelnen Kämpfe von S2 und SWS auf der Minute-zu-Sub-Sekunde-Zeitskala bestehen, die durch die variable Präsenz von SWA im Laufe eines Kampfes 5 , 6 , aber auch durch EEG- und Feldpotential-Rhythmen ausführlich dokumentiert wird Höhere Frequenzen, einschließlich Spindelwellen im Sigma-Band (10-15 Hz) und Gamma-Rhythmen (80 - 120 Hz) (für eine Überprüfung siehe 7 , 8 , 9 , 10 ). Anstatt subtil zu sein, verschieben diese Variationen den schlafenden kortikalen Zustand beim Menschen auf die Extreme des Spektrums. Für Nicht-REM - Schlaf, diese reichen von einer Dominanz von SWA zu Staaten , dass ungefähre wake-artiger Aktivität , weil sie 11 einen wesentlichen Anteil an Hochfrequenzkomponenten enthalten <suP&gt;, 12 Bei Nagetieren und Katzen, obwohl Nicht-REM-Schlaf nicht in Stufen unterteilt ist, tritt eine kurze Periode, die Zwischenschlaf (IS) genannt wird, vor dem REM-Schlaf-Beginn 13 auf . Während des IS werden REM-Schlaf-Features wie Hippocampal-Theta-Aktivität und Ponto-Geniculo-Okzipital-Wellen initiiert, während Nicht-REM-Schlafsignaturen wie Spindelwellen und SWA noch vorhanden sind, was auf eine Mischung zwischen den beiden Schlafzuständen 14 , 15 hinweist. Dennoch könnte IS funktionell unterschiedlich sein, weil es durch Antidepressiva 16 moduliert wird und durch neuartige Objektpräsentation während des vorigen Aufwachens 17 , und es trägt zur Einstellung der Erregungsschwelle 18 bei . Weiterhin zeigen die Zustandsflächen von EEG- und EMG-Parametern frei beweglicher Ratten eine Gruppe von Punkten 14 , die zwischen Nicht-REM-Schlaf, REM-Schlaf und Wachsamkeit kontinuierlich ist. Es gibt auch sporadische Abnahmen in der SWA, ohne in den Wach- oder REM-Schlaf einzutreten, was zu erheblichen Schwankungen der relativen Präsenz der nieder- und hochfrequenten Komponenten während eines konsolidierten Nicht-REM-Schlafkampfes 14 , 19 , 20 führt . Schließlich treten variable Verhältnisse von SWA und höherfrequenten Rhythmen während des Nicht-REM-Schlafes nicht nur zeitlich auf, sondern zeigen auch regionale Unterschiede in der Amplitude und Synchronisation zwischen den kortikalen Bereichen 19 . Säugetier Nicht-REM-Schlaf ist weit von Uniform. Ob diese Ungleichförmigkeit jedoch zu Zuständen führt, die sich in Funktions- und Verhaltensattributen unterscheiden, ist nicht klar. Bei verschiedenen Arten von Schlafstörungen wird der kontinuierliche Schlaf durch spontane Erwachungen und unangemessenes motorisches Verhalten gestört. Darüber hinaus zeigen Spektralanalysen Veränderungen in der relativen Präsenz höherer Frequenzen im EEG 21Und in autonomen Parametern wie Atemnoten und Herzschlag 22 . Die geordnete Abfolge von stabilen Schlafzuständen ist also gestört, und Elemente der kortikalen und / oder autonomen Erregung dringen unkontrolliert ein. Daher ist das Verständnis des Kontinuums der Schlafzustände für Krankheiten von Bedeutung. Darüber hinaus ist die Störung des Schlafes durch Umgebungslärm in städtischen Umgebungen mit allgemeinen Gesundheitsrisiken verbunden, was es entscheidend macht, Momente der erhöhten Verwundbarkeit während des Schlafes zu identifizieren 23 . Verhaltenserregung Versuche beim Menschen Schlaf zeigen an, dass es am schwersten ist aus aufzuwecken SWA dominierten Nicht-REM - Schlaf (Stufe S3), während Licht nicht-REM - Schlaf (Stufe S2) und REM - Schlaf zeigen vergleichbare und unteren Erregungsschwellen 4. Die kortikale Verarbeitung von kurzen Schallreizen variiert im wesentlichen zwischen REM-Schlaf, S2 und S3 24 ,25 , was anzeigt, dass staatsspezifische kortikale Aktivitätsmuster die ersten Stadien der sensorischen Verarbeitung modulieren. Für Nicht-REM-Schlaf beim Menschen variiert die Neigung zum Aufwachen als Reaktion auf Lärm mit dem Vorhandensein von Spindelwellen und Alpha-Rhythmen im EEG 26 , 27 , 28 . Thalamokortikalen rhythmicity während Spindeln wird durch verbesserte synaptische Hemmung bei beiden thalamischen und kortikalen Ebenen begleitet, die auf die Dämpfung der sensorischen Verarbeitung 7 beitragen gedacht wird. Wie sind geräuschresistente und verwundbare Zeiträume in der Zeit organisiert und was sind ihre Determinanten? Bei Mäusen und Menschen haben wir vor kurzem eine infra-langsame, 0,02-Hz-Oszillation in neuronalen Rhythmen identifiziert. Abhängig von der Phase dieser 0,02-Hz-Oszillation zeigten Mäuse eine variable Reaktivität gegenüber externen Reizen, entweder aufwachen oder schlafenGh das Geräusch Interessanterweise war diese Oszillation mit der Rate des Herzschlags korreliert, was darauf hinweist, dass das autonome Nervensystem an der Modulation der Anfälligkeit des Schlafes an äußere Reize beteiligt ist 1 . Gedächtnisbezogene hippocampale Rhythmen wurden auch in diesem Rhythmus organisiert, und am auffallendsten war seine Stärke mit der Qualität der Gedächtniskonsolidierung beim Menschen korreliert. Die 0,02-Hz-Oszillation scheint also ein organisatorisches Prinzip des Nagetier- und menschlichen Nicht-REM-Schlafes zu sein, das sowohl die Empfindlichkeit für die Umwelt als auch die interne Speicherverarbeitung moduliert. Dies unterstreicht erneut die Notwendigkeit von multiparametrischen und kontinuierlichen Einschätzungen von Schlafzuständen, um ihre Funktionalität zu erkennen und Orte von potentieller Verwundbarkeit zu identifizieren. Hier präsentieren wir ein Verfahren zur Extraktion der Wellenform dieser Dynamik, einschließlich der chirurgischen Implantation von Mäusen für kombinierte EEG / ECoG- und EMG-EKG-Messungen, Exposition gegenüber sensorischen Reizen, aAnalyseanalyse. Diese Prozedur stellt eine Grundlage für die Betrachtung des Schlafes als ein kontinuierlich variierender, aber stark organisierter Vigilanzzustand dar, während dessen verschiedene grundlegende Schlaffunktionen sequentiell ausgeführt werden. Allgemeiner ist das Verfahren auf Ansätze anwendbar, die darauf abzielen, die spektralen und autonomen Merkmale zu extrahieren, die einem Verhaltensergebnis während des Schlafes sowohl im Gesundheits- als auch im Krankheitszustand vorausgehen.

<table><tbody><tr><td>2-components epoxy glue</td><td>Henkel</td><td>Loctite EA 3450</td><td></td></tr><tr><td>Absorbable Suturing Fiber (Prolene)</td><td>Ethicon</td><td>5-0 FS-3</td><td></td></tr><tr><td>Adson Forceps</td><td>FST</td><td>11006-12</td><td></td></tr><tr><td>Antiseptic swab</td><td>VWR</td><td>149-0332</td><td></td></tr><tr><td>Attane Isoflurane</td><td>Piramal</td><td>Isoflurane 250mL</td><td></td></tr><tr><td>Connectors 3 x 2-channels</td><td>ENA AG</td><td>2.316</td><td>Raster 2.54 x 2.54 mm; size 5 x 8 x 9 mm; pin size 5 mm; http://www.ena.ch/</td></tr><tr><td>Dragonfly commutator</td><td>Dragonfly</td><td>Model #SL-10</td><td></td></tr><tr><td>EMBLA amplifier</td><td>EMBLA</td><td>A10 amplifier</td><td></td></tr><tr><td>Fine scissors</td><td>FST</td><td>14108-09</td><td></td></tr><tr><td>Flat Head Gold-plated steel screw</td><td>J.I. Morris</td><td>FF00CE125</td><td>https://jimorrisco.com/</td></tr><tr><td>Gold wire</td><td>CMSA</td><td>T.69 5gr</td><td>http://www.cmsa.ch/en/</td></tr><tr><td>Hemostatic sponge</td><td>Pfizer</td><td>Gelfoam</td><td></td></tr><tr><td>iodine-based disinfectant (Betadine)</td><td>Mundipharma</td><td>standart solution 60mL</td><td></td></tr><tr><td>Komet drill steel 1/005PM104</td><td>UNOR AG</td><td>22310</td><td></td></tr><tr><td>Matlab Analysis Software</td><td>MathWorks</td><td>R2016b</td><td>https://ch.mathworks.com/products/matlab.html</td></tr><tr><td>Microdrill</td><td>Fine Science Tools</td><td>96758</td><td></td></tr><tr><td>Mouse Gas Anesthesia Head Holder</td><td>Kopf Instruments</td><td>Model 923-B</td><td>http://kopfinstruments.com/product/model-923-b-mouse-gas-anesthesia-head-holder/</td></tr><tr><td>Ophtalmic ointment</td><td>Pharmamedica</td><td>VITA-POS</td><td></td></tr><tr><td>Paladur (liquid)</td><td>UNOR AG</td><td>2260215</td><td>for dental cement</td></tr><tr><td>Palavit (powder)</td><td>UNOR AG</td><td>5410929</td><td>for dental cement</td></tr><tr><td>Small Animal Stereotaxic Frame</td><td>Kopf Instruments</td><td>Model 930</td><td>http://kopfinstruments.com/product/model-930-small-animal-stereotaxic-frame-assembly/</td></tr><tr><td>Soldering wire</td><td>Stannol</td><td>593072</td><td></td></tr><tr><td>Temperature controller - Mini rectal probe</td><td>Phymep</td><td>4090502</td><td>http://www.phymep.com/produit/dc-temperature-controller/</td></tr><tr><td>Temperature controller- heating pad</td><td>Phymep</td><td>4090205</td><td>http://www.phymep.com/produit/dc-temperature-controller/</td></tr></tbody></table>

quantifying infra-slow dynamics of spectral power and heart rate in sleeping mice

Drei Wachsamkeitsstaaten dominieren das Leben der Säugetiere: Wakefulness, nicht-schnelle Augenbewegung (Nicht-REM) Schlaf und REM-Schlaf. Da mehr neuronale Korrelate des Verhaltens in frei bewegten Tieren identifiziert werden, wird diese dreifache Unterteilung zu einfach. Während der Wachsamkeit definieren Ensembles der globalen und lokalen kortikalen Aktivitäten zusammen mit peripheren Parametern wie Pupillendurchmesser und sympathovagalem Gleichgewicht verschiedene Grade der Erregung. Es bleibt unklar, inwieweit der Schlaf auch ein Kontinuum von Hirnzuständen bildet, in dem der Grad der Widerstandsfähigkeit gegenüber sensorischen Reizen und Erregbarkeit und vielleicht anderen Schlaffunktionen allmählich variiert und wie sich die peripheren physiologischen Zustände zusammenhängen. Die Forschung, die die Methoden zur Überwachung mehrerer Parameter während des Schlafes vorantreibt, sowie die Zuordnung zu den Konstellationen dieser funktionalen Attribute, ist von zentraler Bedeutung, um unser Verständnis des Schlafes als multifunktionalen Prozess zu verfeinern, in dem viele vorteilhafte Effekte ex sein müssenEcuted Die Identifizierung von neuartigen Parametern, die Schlafzustände charakterisieren, eröffnet Chancen für neuartige diagnostische Wege bei Schlafstörungen. Wir zeigen ein Verfahren zur Beschreibung von dynamischen Variationen von Maus-Nicht-REM-Schlafzuständen über die kombinierte Überwachung und Analyse von Elektroenzephalogramm (EEG) / Elektrokortikogramm (ECoG), Elektromyogramm (EMG) und Elektrokardiogramm (EKG) unter Verwendung von standardpolysomnographischen Aufzeichnungsverfahren. Mit diesem Ansatz fanden wir, dass der Maus-Nicht-REM-Schlaf in Zyklen von koordinierten neuralen und kardialen Oszillationen organisiert ist, die aufeinanderfolgende 25-s-Intervalle von hoher und niedriger Zerbrechlichkeit zu externen Reizen erzeugen. Daher werden zentrale und autonome Nervensysteme koordiniert, um verhaltensbedingte Schlafzustände während des konsolidierten Nicht-REM-Schlafes zu bilden. Wir präsentieren chirurgische Manipulationen für polysomnographische ( dh EEG / EMG kombinierte mit EKG) Überwachung, um diese Zyklen in der frei schlafenden Maus, die Analyse zu quanti zu verfolgenIhre Dynamik und die akustischen Stimulationsprotokolle, um ihre Rolle in der Wahrscheinlichkeit des Aufwachens zu beurteilen. Unser Ansatz wurde bereits auf den menschlichen Schlaf ausgedehnt und verspricht, gemeinsame organisatorische Prinzipien von Nicht-REM-Schlafzuständen bei Säugetieren aufzuklären.

Abbildung 2 A (obere Platte) zeigt 100-minütige Abschnitte des spontanen Schlaf-Wach-Verhaltens, aufgezeichnet durch polysomnographische Elektroden, die wie beschrieben implantiert wurden (siehe Abbildung 1 ). Die Erhöhungen und Abnahmen der EEG- und EMG-Amplitude bei Nicht-REM-Schlafbeginn sind deutlich sichtbar. Der intermittierende REM-Schlaf ist durch eine Abnahme der EEG-Amplitude und eine weitere Abnahme...

Watch this Scientific Journal Video about Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice at JoVE.com

Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice

Hier stellen wir experimentelle und analytische Verfahren vor, um die zeitliche Dynamik der neuronalen und kardialen Variablen des Nicht-REM-Schlafes bei Mäusen zu beschreiben, die die Schlafreaktion auf akustische Reize modulieren.

Quantifizierung der infra-langsamen Dynamik der spektralen Kraft und der Herzfrequenz bei schlafenden Mäusen

Three vigilance states dominate mammalian life: wakefulness, non-rapid eye movement (non-REM) sleep, and REM sleep. As more neural correlates of behavior ...

quantifying-infra-slow-dynamics-spectral-power-heart-rate-sleeping

Research

JoVE Journal

Neuroscience

9.9K Aufrufe.  University of Lausanne.  Hier stellen wir experimentelle und analytische Verfahren vor, um die zeitliche Dynamik der neuronalen und kardialen Variablen des Nicht-REM-Schlafes bei Mäusen zu beschreiben, die die Schlafreaktion auf akustische Reize modulieren. 

Serie: Quantifying Infra-slow Dynamics of Spectral Power and Heart Rate in Sleeping Mice

Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy

In epilepsy, seizures can evoke cardiac rhythm disturbances such as heart rate changes, conduction blocks, asystoles, and arrhythmias, which can potentially increase risk of sudden unexpected death in epilepsy (SUDEP). Electroencephalography (EEG) and electrocardiography (ECG) are widely used clinical diagnostic tools to monitor for abnormal brain and cardiac rhythms in patients. Here, a technique to simultaneously record video, EEG, and ECG in mice to measure behavior, brain, and cardiac activities, respectively, is described. The technique described herein utilizes a tethered (i.e., wired) recording configuration in which the implanted electrode on the head of the mouse is hard-wired to the recording equipment. Compared to wireless telemetry recording systems, the tethered arrangement possesses several technical advantages such as a greater possible number of channels for recording EEG or other biopotentials; lower electrode costs; and greater frequency bandwidth (i.e., sampling rate) of recordings. The basics of this technique can also be easily modified to accommodate recording other biosignals, such as electromyography (EMG) or plethysmography for assessment of muscle and respiratory activity, respectively. In addition to describing how to perform the EEG-ECG recordings, we also detail methods to quantify the resulting data for seizures, EEG spectral power, cardiac function, and heart rate variability, which we demonstrate in an example experiment using a mouse with epilepsy due to Kcna1 gene deletion. Video-EEG-ECG monitoring in mouse models of epilepsy or other neurological disease provides a powerful tool to identify dysfunction at the level of the brain, heart, or brain-heart interactions.

Here, we present a protocol to record brain and heart bio signals in mice using simultaneous video, electroencephalography (EEG), and electrocardiography (ECG). We also describe methods to analyze the resulting EEG-ECG recordings for seizures, EEG spectral power, cardiac function, and heart rate variability.

Gleichzeitige Video-EEG-EKG Monitoring Neurocardiac Dysfunktion in Mausmodellen der Epilepsie zu identifizieren

In epilepsy, seizures can evoke cardiac rhythm disturbances such as heart rate changes, conduction blocks, asystoles, and arrhythmias, which can ...

Forschung

Genetik

Implantation of Radiotelemetry Transmitters Yielding Data on ECG, Heart Rate, Core Body Temperature and Activity in Free-moving Laboratory Mice

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas.
In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters1, 2.
Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals3, 4. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks3, 5.
Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice5, 6.

A surgical technique for implantation of commercially available telemetry transmitters used for continuous measurement of biopotential (one-lead ECG), heart rate, core body temperature and locomotor activity in freely moving mice is shown. Recommendations and protocols for post-operative care and pain relief, improving recovery, well being and survival rate are also presented.

Die Implantation von Radiotelemetrie Sender Nachgeben Daten über EKG, Herzfrequenz, Körpertemperatur und Aktivität in frei bewegliche Labormäusen

The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a ...

Medizin

Noninvasive, High-throughput Determination of Sleep Duration in Rodents

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a long recovery period. To perform an EEG recording, the animal is connected to a receiver, creating an unnatural tether to the head-mount. EEG monitoring is time consuming, carries risk to the animal, and is not a completely natural setting for the measurement of sleep. Alternative methods to detect sleep, particularly in a high-throughput fashion, would greatly advance the field of sleep research. Here, we describe a validated method for detecting sleep via activity-based home-cage monitoring. Previous studies have shown that sleep assessed via this method has a high degree of agreement with sleep defined by traditional EEG-based measures. Whereas this method is validated for total sleep time, it is important to note that sleep bout duration should be assessed by an EEG which has better temporal resolution. The EEG can also differentiate rapid eye movement (REM) and non-REM sleep, giving more detail about the exact nature of sleep. Nevertheless, activity-based sleep determination can be used to analyze multiple days of undisturbed sleep and to assess sleep as a response to an acute event (like stress). Here, we show the power of this system to detect the response of mice to daily intraperitoneal injections.

We describe a high-throughput method of measuring sleep by means of activity-based home-cage monitoring. This method offers advantages over traditional EEG-based methods. It is well validated for the determination of total sleep duration and can be a powerful tool to monitor sleep in rodent models of human disease.

Nicht-invasive High-Throughput-Bestimmung der Schlafdauer bei Nagern

Traditionally, sleep is monitored by an electroencephalogram (EEG). EEG studies in rodents require surgical implantation of the electrodes followed by a ...

Verhalten

Real-Time Proxy-Control of Re-Parameterized Peripheral Signals using a Close-Loop Interface

The fields that develop methods for sensory substitution and sensory augmentation have aimed to control external goals using signals from the central nervous systems (CNS). Less frequent however, are protocols that update external signals self-generated by interactive bodies in motion. There is a paucity of methods that combine the body-heart-brain biorhythms of one moving agent to steer those of another moving agent during dyadic exchange. Part of the challenge to accomplish such a feat has been the complexity of the setup using multimodal bio-signals with different physical units, disparate time scales and variable sampling frequencies.
In recent years, the advent of wearable bio-sensors that can non-invasively harness multiple signals in tandem, has opened the possibility to re-parameterize and update the peripheral signals of interacting dyads, in addition to improving brain- and/or body-machine interfaces. Here we present a co-adaptive interface that updates efferent somatic-motor output (including kinematics and heart rate) using biosensors; parameterizes the stochastic bio-signals, sonifies this output, and feeds it back in re-parameterized form as visuo/audio-kinesthetic reafferent input. We illustrate the methods using two types of interactions, one involving two humans and another involving a human and its avatar interacting in near real time. We discuss the new methods in the context of possible new ways to measure the influences of external input on internal somatic-sensory-motor control.

We present protocols and methods of analyses to build co-adaptive interfaces that stream, parameterize, analyze, and modify human body and heart signals in close-loop. This setup interfaces signals derived from the peripheral and central nervous systems of the person with external sensory inputs to help track biophysical change.

Echtzeit-Proxy-Steuerung von re-parametrisierten Peripheriesignalen über eine Close-Loop-Schnittstelle

The fields that develop methods for sensory substitution and sensory augmentation have aimed to control external goals using signals from the central ...

Polygraphic Recording Procedure for Measuring Sleep in Mice

Recording of the epidural electroencephalogram (EEG) and electromyogram (EMG) in small animals, like mice and rats, has been pivotal to study the homeodynamics and circuitry of sleep-wake regulation. In many laboratories, a cable-based sleep recording system is used to monitor the EEG and EMG in freely behaving mice in combination with computer software for automatic scoring of the vigilance states on the basis of power spectrum analysis of EEG data. A description of this system is detailed herein. Steel screws are implanted over the frontal cortical area and the parietal area of 1 hemisphere for monitoring EEG signals. In addition, EMG activity is monitored by the bilateral placement of wires in both neck muscles. Non-rapid eye movement (Non-REM; NREM) sleep is characterized by large, slow brain waves with delta activity below 4 Hz in the EEG, whereas a shift from low-frequency delta activity to a rapid low-voltage EEG in the theta range between 6 and 10 Hz can be observed at the transition from NREM to REM sleep. By contrast, wakefulness is identified by low- to moderate-voltage brain waves in the EEG trace and significant EMG activity.

The recording of electroencephalogram (EEG) and electromyogram (EMG) in freely behaving mice is a critical step to correlate behavior and physiology with sleep and wakefulness. The experimental protocol described herein provides a cable-based system for acquiring EEG and EMG recordings in mice.

Polygraphic Recording Verfahren zur Messung von Schlaf bei Mäusen

Recording of the epidural electroencephalogram (EEG) and electromyogram (EMG) in small animals, like mice and rats, has been pivotal to study the ...

Neurowissenschaften

Novel Approach for Simultaneous Recording of Renal Sympathetic Nerve Activity and Blood Pressure with Intravenous Infusion in Conscious, Unrestrained Mice.

Renal sympathetic nerves contribute significantly to both physiological and pathophysiological phenomena. Evaluating renal sympathetic nerve activity (RSNA) is of great interest in many areas of research such as chronic kidney disease, hypertension, heart failure, diabetes and obesity. Unequivocal assessment of the role of the sympathetic nervous system is thus imperative for proper interpretation of experimental results and understanding of disease processes. RSNA has been traditionally measured in anesthetized rodents, including mice. However, mice usually exhibit very low systemic blood pressure and hemodynamic instability for several hours during anesthesia and surgery. Meaningful interpretation of RSNA is confounded by this non-physiological state, given the intimate relationship between sympathetic nervous tone and cardiovascular status. To address this limitation of traditional approaches, we developed a new method for measuring RSNA in conscious, freely-moving mice. Mice were chronically instrumented with radio-telemeters for continuous monitoring of blood pressure as well as a jugular venous infusion catheter and custom-designed bipolar electrode for direct recording of RSNA. Following a 48-72 hour recovery period, survival rate was 100% and all mice behaved normally. At this time-point, RSNA was successfully recorded in 80% of mice, with viable signals acquired up to 4 and 5 days post-surgery in 70% and 50% of mice, respectively. Physiological blood pressures were recorded in all mice (116&plusmn;2 mmHg; n=10). Recorded RSNA increased with eating and grooming, as well-established in the literature. Furthermore, RSNA was validated by ganglionic blockade and modulation of blood pressure with pharmacological agents. Herein, an effective and manageable method for clear recording of RSNA in conscious, freely-moving mice is described.

Anesthetized mice exhibit non-physiological systemic blood pressure, which precludes meaningful assessment of autonomic tone given the intimate relationship between blood pressure and the autonomic nervous system. Thus, a novel method to simultaneously record renal sympathetic nerve activity and blood pressure with intravenous infusion in conscious mice is outlined.

Neuer Ansatz zur gleichzeitigen Erfassung von renalen sympathischen Nerven-Aktivität und Blutdruck mit intravenösen Infusion in dem Bewusstsein, hemmungslose Mäuse.

Renal sympathetic nerves contribute significantly to both physiological and pathophysiological phenomena. Evaluating renal sympathetic nerve activity ...

Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed in mice is high. Phenotypic characterization of these mouse models also requires the examination of cardiac function and morphology. Echocardiography and magnetic resonance imaging (MRI) are commonly used approaches to characterize cardiac function and morphology in mice. Echocardiographic and MRI equipment specialized for use in small rodents is&#160;expensive and requires a dedicated space. This protocol describes cardiac measurements in mice using a clinical echocardiographic system with a 15 MHz human vascular probe. Measurements are performed on anesthetized adult mice. At least three image sequences are recorded and analyzed for each animal in M-mode in the parasternal short-axis view. Afterwards, cardiac histological examination is performed, and cardiomyocyte diameters are determined on hematoxylin-eosin- or wheat germ agglutinin (WGA)-stained paraffin sections. Vessel density is determined morphometrically after Pecam-1 immunostaining. The protocol has been applied successfully to pharmacological studies and different genetic animal models under baseline conditions, as well as after experimental myocardial infarction by the permanent ligation of the left anterior descending coronary artery (LAD). In our experience, echocardiographic investigation is limited to anesthetized animals and is feasible in adult mice weighing at least 25 g.

Echocardiographic examination is frequently used in mice. Expensive high-resolution ultrasound devices have been developed for this purpose. This protocol describes an affordable echocardiographic procedure combined with histological morphometric analyses to determine cardiac morphology.

Echokardiographische und histologische Untersuchung der kardiale Morphologie in der Maus

An increasing number of genetically modified mouse models has become available in recent years. Moreover, the number of pharmacological studies performed ...

Echocardiographic Measurement of Right Ventricular Diastolic Parameters in Mouse

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV diastolic function is rarely quantified in experimental studies. This might be due to technical difficulties in the visualization of the RV in the apical four-chamber view in rodents. Here we describe two positions facilitating the visualization of the apical four-chamber view in mice to assess the RV diastolic function.
The apical four-chamber view is enabled by tilting the mouse fixation platform to the left and caudally (LeCa) or to the right and cranially (RiCr). Both positions provide images of comparable quality. The results of the RV diastolic function obtained from two positions are not significantly different. Both positions are comparably easy to perform. This protocol can be incorporated into published protocols and enables detailed investigations of the RV function.

Here we describe and compare two positions for obtaining the apical four-chamber view in mice. These positions enable the quantification of the right ventricular function, provide comparable results, and can be used interchangeably.

Echokardiographische Messung rechtsventrikulärer diastolischer Parameter in der Maus

Diastolic dysfunction is a prominent feature of right ventricular (RV) remodeling associated with conditions of pressure overload. However, the RV ...

Computer-based Multitaper Spectrogram Program for Electroencephalographic Data

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. This paper describes a Windows-based, open source code for creating EEG multitaper spectrograms. The compiled program is accessible to Windows users without software licensing. For Macintosh users, the program is limited to those with a MATLAB software license. The program is illustrated via EEG spectrograms that vary as a function of states of sleep and wakefulness, and opiate-induced alterations in those states. The EEGs of C57BL/6J mice were wirelessly recorded for 4 h after intraperitoneal injection of saline (vehicle control) and antinociceptive doses of morphine, buprenorphine, and fentanyl. Spectrograms showed that buprenorphine and morphine caused similar changes in EEG power at 1&#8722;3 Hz and 8&#8722;9 Hz. Spectrograms after administration of fentanyl revealed maximal average power bands at 3 Hz and 7 Hz. The spectrograms unmasked differential opiate effects on EEG frequency and power. These computer-based methods are generalizable across drug classes and can be readily modified to quantify and display a wide range of rhythmic biological signals.

This protocol provides an open source, compiled MATLAB program that generates multitaper spectrograms for electroencephalographic data.

Computerbasiertes Multitaper-Spektrogrammprogramm für elektroenzephalographische Daten

Current web resources provide limited, user friendly tools to compute spectrograms for visualizing and quantifying electroencephalographic (EEG) data. ...

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. The baroreflex is a key homeostatic mechanism to counteract acute, short-term changes in arterial BP and to maintain BP in a relatively narrow physiological range. BP is sensed by baroreceptors located in the aortic arch and carotid sinus. When BP changes, signals are transmitted to the central nervous system and are then communicated to the parasympathetic and sympathetic branches of the autonomic nervous system to adjust HR. A rise in BP causes a reflex decrease in HR, a drop in BP causes a reflex increase in HR.
Baroreflex sensitivity (BRS) is the quantitative relationship between changes in arterial BP and corresponding changes in HR. Cardiovascular diseases are often associated with impaired baroreflex function. In various studies reduced BRS has been reported in e.g., heart failure, myocardial infarction, or coronary artery disease. 
Determination of BRS requires information from both BP and HR, which can be recorded simultaneously using telemetric devices. The surgical procedure is described beginning with the insertion of the pressure sensor into the left carotid artery and positioning of its tip in the aortic arch to monitor arterial pressure followed by the subcutaneous placement of the transmitter and ECG electrodes. We also describe postoperative intensive care and analgesic management. After a two-week period of post-surgery recovery long-term ECG and BP recordings are performed in conscious and unrestrained mice. Finally, we include examples of high-quality recordings and the analysis of spontaneous baroreceptor sensitivity using the sequence method.

The baroreflex is a heart-rate regulation mechanism by the autonomic nervous system in response to blood-pressure changes. We describe a surgical technique to implant telemetry transmitters for continuous and simultaneous measurement of electrocardiogram and blood pressure in mice. This can determine spontaneous baroreflex sensitivity, an important prognostic marker for cardiovascular disease.

Implantation von kombinierten telemetrischen EKG- und Blutdrucktransmittern zur Bestimmung der spontanen Baroreflexsensitivität bei bewussten Mäusen

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. ...