Die Autoren möchten Gehalt Auszeichnungen, Ausrüstung Zuschüsse und operativen Mitteln aus dem Fonds de la recherche en santé Québec (FRSQ), Canadian Institutes of Health Research (CIHR), dem Natural Sciences and Engineering Research Council of Canada (NSERC) anerkennen, und der Concordia University Research Chairs-Programm (cruc), sowie die durchdachte Feedback zu diesem Manuskript von Dr. Jane Stewart.

Ein. Tierhaltung <ol><li> Cage: Um die Laufradbremsteil Aktivität eines individuellen Nager aufnehmen, jeder Käfig sollte ein einzelnes Nagetier und Laufradbremsteil unterzubringen. Da Laufräder kann als eine Form der Bereicherung, sollten alle Nager in keiner Studie haben ähnliche Zugang zu einem Laufrad. </li><li> Bedding Veränderungen: Animal Handling sowie Änderungen in Käfigen oder Bettwäsche haben alle nicht-photic Auswirkungen auf circadiane Rhythmen 21-23, so sind Käfige mit Mesh-Belag ideal, weil sie Kontakt mit dem Tier zu minimieren. Ungeachtet der Verfügbarkeit eines solchen Fach-System, sollten Bettwäsche Veränderungen während der kritischen Phasen eines Experiments vermieden werden. Alternativen umfassen die Verwendung langlebiger Bettzeug, das für weitere seltene Käfig Veränderungen erlauben würde, oder das Ändern Käfige auf einer pseudo-zufälligen Zeitplan. </li><li> Isolation Boxes: Käfige sollten in Isolation Boxen, schallgedämpften, Licht-co sind gehalten werdenntrolled und gut belüftet sein. Je nach Größe und Ausgestaltung der Isolation Boxen, wird die Anzahl von Käfigen in jedem Kasten typischerweise 1-8 liegen. Bei Unterbringung mehrerer Käfige in einem einzigen Isolation Box, sollte man sich bewusst sein, dass verschiedene Gerüche und Geräusche von anderen Tieren können verwirrende Effekte auf das circadiane Verhalten der einzelnen Tiere haben. Um diese Probleme zu vermeiden, sollte man versuchen, ein Käfig pro Isolierbox unterzubringen. </li><li> Ventilation: Angemessene Luftstrom unbedingt machen die Boxen ein komfortables Wohnumfeld für Nager. Der Ventilator in jedem Kasten sollte Kapuze, um Licht von außerhalb des Kastens verhindern vom Erreichen der Innenseite. Auch die Fans in der Regel entfernen, Luft aus der Box und blasen sie in den Raum. Kleine lichtdichte Öffnungen ermöglichen eine Luftzirkulation, um die Trennung Boxen von mehreren Punkten geben und helfen, unangenehme Brise zu vermeiden. Um zu verifizieren, dass es eine ausreichende Belüftung, die Temperatur im Inneren der Isolation Box (wenngeschlossen für mehrere Stunden, mit eingeschalteter Beleuchtung) sollte praktisch identisch mit der Temperatur in dem Raum, in dem es untergebracht ist. </li><li> Beleuchtung: Environmental Lichtintensität sollten die gleichen sein in allen Käfigen. Vereinbaren Sie einen einzigen Licht an einer ähnlichen Stelle übereinander Käfig, und verwenden Sie immer die gleiche Marke / Typ der Glühbirne. Verwenden moderate Beleuchtungsintensität (100-300 Lux) bei Käfig-Ebene. Vermeiden Sie zu hohe Beleuchtungsstärke, die eher direkte Änderungen auf das Verhalten auf die Licht statt des circadianen Systems, per se (zB Maskierung) produzieren. </li><li> Darkness / Dim roter Beleuchtung: Wenn es notwendig zu handhaben oder zu behandeln Tiere im Dunkeln (zB in konstanter Dunkelheit oder Nacht) ist, Nachtsichtgeräte verwendet werden soll. Alternativ, da das circadiane System ist relativ unempfindlich gegenüber der roten Wellenlängen können schwach rot Beleuchtung verwendet werden. Die spezifische rote Licht, das Sie verwenden sollten getestet, um sicherzustellen, dass nicht Alte werdenr Laufradbremsteil Aktivität (zB Maskierung) oder stellen Sie die circadianen Uhr (zB eine Phasenverschiebung). </li></ol> 2. Data Collection (siehe Abbildung 1 - Vitalview Hardware-Konfiguration) <ol><li> Laufräder: Der Durchmesser und die Ergonomie des Laufrades wird sich ändern die Menge der Nutzung 24. So verwenden kleinere und leichtere Räder für Mäuse und größeren schwereren Räder für Ratten. Beim Waschen und neu zu installieren Räder, sicherzustellen, dass die Räder in der Lage, freie, nicht &quot;wackeln&quot;, und dass die Aufnahme Mikro-Schalter werden von jeder Umdrehung des Rades aktiviert Spin sind. </li><li> Mikroschalter: Jede Umdrehung des Laufrades sollte eine magnetische oder mechanische Mikroschalter zu aktivieren. Informationen aus dem Mikro-Schalter über einen einzigen Kanal übertragen werden und von einem Computer, der die Daten können Behälter über die Zeit (zB alle 2, 5, 6 oder 10 min). </li><li> Computer-Hardware: Unsere Running-Rad-Aufnahmen sind mit Vitalview, eine Hard-und Softwareplattform von Mini Mitter (entwickelt aus <a href="http://www.minimitter.com/vitalview_software.cfm" target="_blank">http://www.minimitter.com/vitalview_software.cfm</a> ). Es gibt jedoch andere Aufnahme Plattformen wie ClockLab durch Actimetrics (entwickelt <a href="http://www.actimetrics.com/ClockLab/" target="_blank">http://www.actimetrics.com/ClockLab/</a> ). Beide Plattformen zusammenbringen Daten aus vielen einkanaligen Quellen (zB ein einzelnes Mikroschalter durch eine einzige Laufrad aktiviert) in einer einzigen Computerdatei. Daten von einzelnen Kanäle können dann grafisch dargestellt und separat zu einem späteren Zeitpunkt analysiert. </li></ol> 3. Daten Recordings <ol><li> Files: Die oben genannten Software-Plattformen verwendet zu trennen einzelnen Kanäle, so dass einzelne Dateien für jeden Lauf-Rad-Datensatz erstellt werden. Solche Daten sind am besten visualisiert und grafisch mit speziell designed Programmen wie ActiView (Minimitter, Bend, OR), Circadia oder Clocklab (Actimetrics, Wilmette, IL), die alle produzieren kann Periodogramme und actograms. Allerdings kann Einkanal-Dateien auch geöffnet und analysiert werden mit allgemeinen Tabellenkalkulationsprogramme wie Excel (Microsoft, Redmond, WA). </li><li> Berechnung Circadian Time (CT): CT 12 ist, per Definition, der Beginn der Lauf-Rad-Aktivität in nachtaktiven Nager. Parallel mit dem 24-Stunden-Tag, durch Vereinbarung, ein circadianen Tages in 24 zirkadianen hr gebrochen. Wenn demgemäß die freilaufende circadiane beträgt 24 h 30 min, wie durch die Wand Uhr gemessen wird CT 0 ca. 12 Std. 15 min nach CT12 auftreten. </li></ol>

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Überwachung der täglichen Aktivität Rhythmen mit Laufrädern ist das am häufigsten verwendete und zuverlässige Methode für die Beurteilung der Ausgang des Masters circadianen Uhr in nachtaktiven Nager. Rad andauernde Aktivität, jedoch ist nur eine von vielen Aspekten des Verhaltens und Physiologie, die kontinuierlich überwacht werden kann. Obwohl die überwiegende Mehrheit der Laufradbremsteil Aktivität auftritt während der Nacht auftritt, über 30% des gesamten Wachheit während des Tages 25,26. We...

<table border="1"&gt;<tbody&gt;<tr&gt;<td<strong&gt; Name des Reagenz</strong</td&gt;<td<strong&gt; Unternehmen</strong</td&gt;<td<strong&gt; Katalog-Nummer</strong</td&gt;<td<strong&gt; Kommentare (optional)</strong</td&gt;</tr&gt;<tr&gt;<td&gt; Vitalview Card &amp; Software</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 855-0030-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; DP24 Dataport</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 840-0024-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; QA4-Module</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 130-0050-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; Magnetschalter</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 130-0015-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; C-50 Schlauchpaket</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 060-0045-10</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; Rat Laufrad Montage</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 640-0700-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; Cage und Fach-Unterstützung</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 640-0400-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; Einsetzbar weggeschnitten Käfig</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 664-2154-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; Grid Boden für Käfig</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 676-2154-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; Stoffauffangbehälter</td&gt;<td&gt; Mini Mitter</td&gt;<td&gt; # 684-2154-00</td&gt;<td&gt; (Bend, OR, USA)</td&gt;</tr&gt;<tr&gt;<td&gt; Lampengehäuse</td&gt;<td&gt; Mikrolithen Scientific</td&gt;<td&gt; # R-101</td&gt;<td&gt; (Toronto, ON, Canada)</td&gt;</tr&gt;<tr&gt;<td&gt; 4W Leuchtstofflampen</td&gt;<td&gt; Mikrolithen Scientific</td&gt;<td&gt; # F4T5/CW</td&gt;<td&gt; (Toronto, ON, Canada)</td&gt;</tr&gt;<tr&gt;<td&gt; Isolation Kammern</td&gt;<td&gt; Custom gebaut</td&gt;<td</td&gt;<td&gt; 28 &quot;H x 20&quot; W x 28 &quot;D ½&quot; Black Melamin.</td&gt;</tr&gt;</tbody&gt;</table

recording and analysis of circadian rhythms in running-wheel activity in rodents

Wenn Nagetieren freien Zugang zu einem Laufrad in ihrem gewohnten Käfig haben, werden freiwilligen Verwendung dieses Rades auf der Tageszeit 1-5 abhängen. Nachtaktiven Nager, darunter Ratten, Hamster und Mäuse sind in der Nacht aktiv und relativ inaktiv während des Tages. Viele andere Verhaltens-und physiologische Messungen zeigen auch Tagesrhythmus, aber bei Nagetieren, dient laufenden Rad-Aktivität als ein besonders zuverlässiges und bequemes Maß der Ausgang des Master zirkadianen Uhr, das suprachiasmatischen Kern (SCN) des Hypothalamus. Im Allgemeinen durch einen Prozess namens Entrainment, wird die tägliche Muster laufen-Rad Aktivität natürlich mit der Umwelt Hell-Dunkel-Zyklus (;: 12 hr-dark zB 12 hr-light LD-Zyklus) auszurichten. Allerdings zirkadianen Rhythmen endogen Mustern im Verhalten, die eine ~ 24 Stunden Zeit zeigen, und in konstanter Dunkelheit andauern generiert. Somit wird in der Abwesenheit eines LD Zyklus können die Aufzeichnung und Analyse der Laufradachse Aktivitätverwendet, um die subjektive Zeit der Tageszeit zu bestimmen. Da diese Rhythmen durch die circadiane Uhr gerichtet sind die subjektive time-of-Tag wird als circadiane Zeit (CT) bezeichnet. Wenn im Gegensatz dazu ein LD-Zyklus vorhanden ist, wird die Zeit der Tageszeit, die von der Umwelt LD Zyklus bestimmt wird als Zeitgeber Zeit (ZT). Obwohl zirkadianen Rhythmen in Laufradbremsteil Tätigkeit typischerweise mit dem SCN Uhr 6-8 verbunden sind, könnte circadianen Oszillatoren in vielen anderen Regionen des Gehirns und des Körpers 9-14 auch an der Regulation der täglichen Aktivität Rhythmen beteiligt werden. Zum Beispiel müssen Tagesrhythmus in lebensmittelverarbeitenden antizipatorische Aktivität nicht erforderlich, die SCN 15,16 und stattdessen mit Veränderungen in der Aktivität der zusätzlichen SCN-Oszillatoren 17-20 korreliert. Somit kann Laufradachse Aktivität Aufzeichnungen liefern wichtige Verhaltensinformation nicht nur über den Ausgang des Master Clock SCN, sondern auch auf die Aktivität der zusätzlichen SCN-Oszillatoren. Im Folgenden descrIBE die Geräte und Methoden zur Erfassung, Analyse und Darstellung zirkadianen Bewegungsaktivität Rhythmen in Labornagern.

<ol><li> Computerprogramme: Spezialisierte Computerprogramme werden typischerweise bei der Erzeugung von actograms und die Berechnung des zirkadianen Periode verwendet. Diese Programme umfassen, sind aber nicht darauf beschränkt ActiView (Minimitter, Bend, OR) und Circadia. </li><li> Actograms: Actograms eine grafische Darstellung der täglichen Muster Laufradbremsteil Aktivität. Es gibt Einzel-aufgetragen (x-Achse = 24 Stunden), und doppelklicken aufgetragen (x-Achse = 48 hr) actograms. Beide Methoden Grunds...

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Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

Zirkadiane Rhythmen in freiwilliger Rades verlaufenden Aktivität in Säugetieren sind fest an den molekularen Schwingungen einer Hauptuhr im Gehirn verbunden ist. Als solche können diese täglichen Rhythmen im Verhalten verwendet, um den Einfluss von genetischen, pharmakologischen und Umweltfaktoren auf das Funktionieren dieser circadianen Uhr zu studieren.

Aufnahme und Analyse der zirkadianen Rhythmen in Laufen-Rad-Aktivität in Nagetiere

When rodents have free access to a running wheel in their home cage, voluntary use of this wheel will depend on the time of day1-5. Nocturnal rodents, ...

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Neuroscience

21.2K Aufrufe.  McGill University. Zirkadiane Rhythmen in freiwilliger Rades verlaufenden Aktivität in Säugetieren sind fest an den molekularen Schwingungen einer Hauptuhr im Gehirn verbunden ist. Als solche können diese täglichen Rhythmen im Verhalten verwendet, um den Einfluss von genetischen, pharmakologischen und Umweltfaktoren auf das Funktionieren dieser circadianen Uhr zu studieren.

Serie: Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents

Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila

Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (&equiv;24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal's endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties.

Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila

We describe procedures for recording daily locomotor activity rhythms of Drosophila and subsequent data analysis. Locomotor activity rhythms are a reliable behavioral output of animal circadian clocks and are used as the standard readout of clock function when studying circadian mutants or examining how the environment regulates the circadian system.

Assaying Bewegungsaktivität zu zirkadianen Rhythmen Study and Sleep Parameter in Drosophila</em

Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (&equiv;24 hr) ...

Forschung

Neurowissenschaften

Getting to Compliance in Forced Exercise in Rodents: A Critical Standard to Evaluate Exercise Impact in Aging-related Disorders and Disease

There is a major increase in the awareness of the positive impact of exercise on improving several disease states with neurobiological basis; these include improving cognitive function and physical performance. As a result, there is an increase in the number of animal studies employing exercise. It is argued that one intrinsic value of forced exercise is that the investigator has control over the factors that can influence the impact of exercise on behavioral outcomes, notably exercise frequency, duration, and intensity of the exercise regimen. However, compliance in forced exercise regimens may be an issue, particularly if potential confounds of employing foot-shock are to be avoided. It is also important to consider that since most cognitive and locomotor impairments strike in the aged individual, determining impact of exercise on these impairments should consider using aged rodents with a highest possible level of compliance to ensure minimal need for test subjects. Here, the pertinent steps and considerations necessary to achieve nearly 100% compliance to treadmill exercise in an aged rodent model will be presented and discussed. Notwithstanding the particular exercise regimen being employed by the investigator, our protocol should be of use to investigators that are particularly interested in the potential impact of forced exercise on aging-related impairments, including aging-related Parkinsonism and Parkinson&#8217;s disease.

Exercise may alleviate behavioral impairments associated with neurodegenerative diseases. Studies of the mechanisms underlying exercise-mediated effects have increased in disease models, but the neurobiological background accompanying these diseases, specifically aging, is likely not considered. Here, we illustrate measures to increase the likelihood of a successful exercise paradigm in aged rats.

Anreise nach Compliance im Zwangsübung in Nagetiere: Eine kritische Standard in Übung Auswirkungen in altersbedingten Erkrankungen und Krankheits Bewerten

There is a major increase in the awareness of the positive impact of exercise on improving several disease states with neurobiological basis; these ...

Verhalten

Measuring Circadian and Acute Light Responses in Mice using Wheel Running Activity

Circadian rhythms are physiological functions that cycle over a period of approximately 24 hours (circadian- circa: approximate and diem: day)1, 2. They are responsible for timing our sleep/wake cycles and hormone secretion. Since this timing is not precisely 24-hours, it is synchronized to the solar day by light input. This is accomplished via photic input from the retina to the suprachiasmatic nucleus (SCN) which serves as the master pacemaker synchronizing peripheral clocks in other regions of the brain and peripheral tissues to the environmental light dark cycle3-7. The alignment of rhythms to this environmental light dark cycle organizes particular physiological events to the correct temporal niche, which is crucial for survival8. For example, mice sleep during the day and are active at night. This ability to consolidate activity to either the light or dark portion of the day is referred to as circadian photoentrainment and requires light input to the circadian clock9. Activity of mice at night is robust particularly in the presence of a running wheel. Measuring this behavior is a minimally invasive method that can be used to evaluate the functionality of the circadian system as well as light input to this system. Methods that will covered here are used to examine the circadian clock, light input to this system, as well as the direct influence of light on wheel running behavior.

This article will review methods that can be used to determine circadian function and light responsiveness in mice.

Mess-und Circadian Akute Licht Responses in Mäuse mit Rad Laufen Activity

Circadian rhythms are physiological functions that cycle over a period of approximately 24 hours (circadian- circa: approximate and diem: day)1, 2.  They ...

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive &#8211; running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals&#8217; wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Here we present a protocol to induce activity-based anorexia (ABA) in female adolescent mice. ABA is a condition of hyperactivity evoked by imposing food restriction on rodents with access to a running wheel. This phenomenon is being used as a model to study the underlying neurobiology of anorexia nervosa.

Unter Verwendung des Activity-based Anorexia Nagetiermodell die neurobiologischen Grundlagen von Anorexia Nervosa Study

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A ...

An Innovative Running Wheel-based Mechanism for Improved Rat Training Performance

This study presents an animal mobility system, equipped with a positioning running wheel (PRW), as a way to quantify the efficacy of an exercise activity for reducing the severity of the effects of the stroke&#160;in rats. This system provides more effective animal exercise training than commercially available systems such as treadmills and motorized running wheels (MRWs). In contrast to an MRW that can only achieve speeds below 20 m/min, rats are permitted to run at a stable speed of 30 m/min on a more spacious and high-density rubber running track supported by a 15 cm wide acrylic wheel with a diameter of 55 cm in this work. Using a predefined adaptive acceleration curve, the system not only reduces the operator error but also trains the rats to run persistently until a specified intensity is reached. As a way to evaluate the exercise effectiveness, real-time position of a rat is detected by four pairs of infrared sensors deployed on the running wheel. Once an adaptive acceleration curve is initiated using a microcontroller, the data obtained by the infrared sensors are automatically recorded and analyzed in a computer. For comparison purposes, 3 week training is conducted on rats using a treadmill, an MRW and a PRW. After surgically inducing middle cerebral artery occlusion (MCAo), modified neurological severity scores (mNSS) and an inclined plane test were conducted to assess the neurological damages to the rats. PRW is experimentally validated as the most effective among such animal mobility systems. Furthermore, an exercise effectiveness measure, based on rat position analysis, showed that there is a high negative correlation between the effective exercise and the infarct volume, and can be employed to quantify a rat training in any type of brain damage reduction&#160;experiments.

This study presents an innovative running wheel-based animal mobility system to quantify an effective exercise activity in rats. A rat-friendly testbed is built, using a predefined adaptive acceleration curve, and a high correlation between the effective exercise rate and the infarct volume suggests the protocol&#39;s potential for stroke prevention experiments.

Eine innovative Laufrad-basierten Mechanismus für die Verbesserung der Ratte Trainingsleistung

This study presents an animal mobility system, equipped with a positioning running wheel (PRW), as a way to quantify the efficacy of an exercise activity ...

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 ...

A Method to Study the Impact of Chemically-induced Ovarian Failure on Exercise Capacity and Cardiac Adaptation in Mice

The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet, the role of exercise, as a preventative measure for CVD risk in post-menopausal women has not been adequately studied. Accordingly, we investigated the impact of voluntary cage-wheel exercise and forced treadmill exercise on cardiac adaptation in menopausal mice. The most commonly used inducible model for mimicking menopause in women is the ovariectomized (OVX) rodent. However, the OVX model has a few dissimilarities from menopause in humans. In this study, we administered 4-vinylcyclohexene diepoxide (VCD) to female mice, which accelerates ovarian failure as an alternative menopause model to study the impact of exercise in menopausal mice. VCD selectively accelerates the loss of primary and primordial follicles resulting in an endocrine state that closely mimics the natural progression from pre- to peri- to post-menopause in humans. To determine the impact of exercise on exercise capacity and cardiac adaptation in VCD-treated female mice, two methods were used. First, we exposed a group of VCD-treated and untreated mice to a voluntary cage wheel. Second, we used forced treadmill exercise to determine exercise capacity in a separate group VCD-treated and untreated mice measured as a tolerance to exercise intensity and endurance.

Two exercise paradigms were tested on a newly developed chemically induced menopausal mouse model to examine the impact of menopause on exercise capacity and cardiac adaption to exercise.

Eine Methode, um die Auswirkungen der Chemisch-induzierte Ovarialinsuffizienz on Exercise Cardiac Kapazität und Anpassung in Mäusen untersucht

The risk of cardiovascular disease (CVD) increases in post-menopausal women, yet, the role of exercise, as a preventative measure for CVD risk in ...

Medizin

Tracking Individual Running Metrics in Mice Using a Voluntary Wheel Running Protocol that Minimizes Social Isolation

Voluntary wheel running (VWR) in rodents is used to evaluate performance and endurance and to simulate exercise. In contrast to other exercise paradigms that require aversive stimulus to induce active movement, wheel running is voluntary. VWR generally consists of placing a running wheel inside the mouse home cage. However, analyzing exercise parameters can typically only be conducted when mice are individually housed, while overall cage effects can be reported when mice are group-housed. Therefore, the current models force experimenters to choose between measuring individual exercise parameters in single-housed mice or measuring group effects in group-housed mice; depending on the research question and model, this could be limiting. 
Therefore, the goal of this method is to demonstrate a protocol that assesses VWR in a mouse model by quantifying running parameters in individual mice, with minimal isolation. We report on device design, preoperative preparations, and experiment setup. Results of a 6-week training protocol using this VWR model suggest it provides sufficient stimulus to increase spatial object recognition memory, comparable to the clinical effect of exercise. This simple and inexpensive model facilitates investigation into the effect of VWR on multiple measurements of wheel activity, minimizing factors that could limit or affect experimental outcomes.

This protocol describes an effective voluntary wheel-running model that can be implemented in various research contexts. Unlike other voluntary running models, this method avoids isolation housing while tracking running metrics in individual mice.

Voluntary wheel running (VWR) in rodents is used to evaluate performance and endurance and to simulate exercise. In contrast to other exercise paradigms ...

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ineffective in many patients. To improve patient care, novel and innovative therapeutic concepts causally targeting arrhythmia mechanisms are needed. To study the complex pathophysiology of arrhythmias, suitable animal models are necessary, and mice have been proven to be ideal model species to evaluate the genetic impact on arrhythmias, to investigate fundamental molecular and cellular mechanisms, and to identify potential therapeutic targets.
Implantable telemetry devices are among the most powerful tools available to study electrophysiology in mice, allowing continuous ECG recording over a period of several months in freely moving, awake mice. However, due to the huge number of data points (&gt;1 million QRS complexes per day), analysis of telemetry data remains challenging. This article describes a step-by-step approach to analyze ECGs and to detect arrhythmias in long-term telemetry recordings using the software, Ponemah, with its analysis modules, ECG Pro and Data Insights, developed by Data Sciences International (DSI). To analyze basic ECG parameters, such as heart rate, P wave duration, PR interval, QRS interval, or QT duration, an automated attribute analysis was performed using Ponemah to identify P, Q, and T waves within individually adjusted windows around detected R waves. 
Results were then manually reviewed, allowing adjustment of individual annotations. The output from the attribute-based analysis and the pattern recognition analysis was then used by the Data Insights module to detect arrhythmias. This module allows an automatic screening for individually defined arrhythmias within the recording, followed by a manual review of suspected arrhythmia episodes. The article briefly discusses challenges in recording and detecting ECG signals, suggests strategies to improve data quality, and provides representative recordings of arrhythmias detected in mice using the approach described above.

Here we present a step-by-step protocol for a semiautomated approach to analyze murine long-term electrocardiography (ECG) data for basic ECG parameters and common arrhythmias. Data are obtained by implantable telemetry transmitters in living and awake mice and analyzed using Ponemah and its analysis modules.

Analyse von Langzeit-Elektrokardiographie-Aufnahmen zum Nachweis von Arrhythmien bei Mäusen

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ...

Analysis of Circadian Photoresponses in Drosophila Using Locomotor Activity

Circadian rhythms are only beneficial to animals if they can be synchronized by changes of ambient conditions. Light and temperature are two dominant environmental parameters that synchronize animal circadian clocks. In Drosophila circadian photo-responses are mediated by a solely blue light photoreceptor named CRYPTOCHROME (CRY). Upon photoreception, CRY changes its conformation and initiates the proteosomal dependent degradation of TIMELESS (TIM). TIM is an important pacemaker protein, thus degradation of TIM will reset the circadian clock. Under constant light conditions (LL), wild type flies quickly become arrhythmic because of the constant degradation of TIM, while flies bearing defects with circadian photo-responses will still be rhythmic. Thus LL triggered arrhythmicity has been used for screening of components in circadian light input pathways. A brief short light pulse in the night can also dramatically shift phases of circadian rhythms. As expected, this phase shift response is reduced in flied with defects in circadian photoresponse. Thus analyzing locomotion behavior rhythmicity under LL or phase changes after short light pulse in constant darkness (DD) are two major methods to study circadian photoresponse. Here we describe how to design and analyze LL and phase response experiments. LL arrhythmicity is suitable for screening light input pathways mutants, whereas phase response validates the results and provide further information for light sensitivity.

Drosophila locomotor activity is a robust and quantitative measurement of circadian photo-responses. We describe protocols for designing behavior experiments for circadian photo-responses and analyzing the data. Studying the circadian photo-responses is important for dissecting the neuronal and molecular mechanisms of light entrainment.

Circadian rhythms are only beneficial to animals if they can be synchronized by changes of ambient conditions. Light and temperature are two dominant ...