The authors would like to acknowledge salary awards, equipment grants, and operating funds from the Fonds de la recherche en sant&eacute; Qu&eacute;bec (FRSQ), Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Concordia University Research Chairs Program (CRUC), as well as the thoughtful feedback on this manuscript from Dr. Jane Stewart.

1. Animal Housing
<ol>
	<li>Cage: In order to record the running-wheel activity of an individual rodent, each cage should house a single rodent and running-wheel. Because running wheels can be considered a form of enrichment, all rodents in any study should have similar access to a running wheel.</li>
	<li>Bedding changes: Animal handling as well as changes in cages or bedding can all have non-photic effects on circadian rhythms21-23, so, cages with mesh-flooring are ideal because they minimize contact with the animal. Notwithstanding the availability of such a tray-system, bedding changes should be avoided during critical phases of an experiment. Alternatives include using longer-lasting bedding, which would allow for more infrequent cage changes, or changing cages on a pseudo-random schedule.</li>
	<li>Isolation Boxes: Cages should be kept in isolation boxes that are sound-attenuated, light-controlled, and well-ventilated. Depending on the size and configuration of the isolation boxes, the number of cages within each box will typically range from 1-8. When housing multiple cages in a single isolation box, one should be aware that various odors and sounds coming from other animals can have confounding effects on the circadian behavior of individual animals. To avoid these problems, one should attempt to house one cage per isolation box.</li>
	<li>Ventilation: Adequate air flow is imperative to making the boxes a comfortable home environment for rodents. The fan in each box should be hooded, so as to prevent light from outside the box from reaching the inside. Also, fans will typically remove air from the box and blow it into the room. Small light-tight vents allow air to enter the isolation boxes from several points, and help to avoid uncomfortable breezes. In order to verify that there is adequate ventilation, the temperature inside the isolation box (when closed for several hours, with the lights on) should be virtually identical to the temperature in the room where it is housed.</li>
	<li>Lighting: Environmental light intensity should be the same in all cages. Arrange a single light at a similar location above each cage, and always use the same brand/type of bulb. Use moderate intensity illumination (100-300 lux) at cage level. Avoid excessively high illumination levels, which are more likely to produce direct changes on behavior attributable to the light rather than the circadian system, per se (e.g. masking).</li>
	<li>Darkness/Dim red lighting: If it is necessary to handle or treat animals in the dark (e.g. in constant darkness or nighttime), night vision goggles should be used. Alternatively, because the circadian system is relatively insensitive to red-wavelengths, dim red lighting can be used. The specific red light you use should be tested to ensure it does not alter running-wheel activity (e.g. masking) or adjust the circadian clock (e.g. produce a phase shift).</li>
</ol>
2. Data Collection (See Figure 1 - Vitalview Hardware Configuration)
<ol>
	<li>Running wheels: The diameter and ergonomics of the running wheel will change the amount of use24. Thus, use smaller and lighter wheels for mice, and larger heavier wheels for rats. When washing and re-installing wheels, ensure that the wheels are able to spin unobstructed, do not "wobble", and that the recording micro-switches are activated by each turn of the wheel.</li>
	<li>Micro-switches: Each revolution of the running wheel should activate a magnetic or mechanical micro-switch. Information from the micro-switch is transmitted via a single channel and recorded by a computer which can bin the data over time (e.g. every 2, 5, 6, or 10 min).</li>
	<li>Computer hardware: Our running-wheel recordings are made with Vitalview, a hardware and software platform developed by Mini Mitter (<a href="http://www.minimitter.com/vitalview_software.cfm" target="_blank">http://www.minimitter.com/vitalview_software.cfm</a>). However, there are other recording platforms such as ClockLab, developed by Actimetrics (<a href="http://www.actimetrics.com/ClockLab/" target="_blank">http://www.actimetrics.com/ClockLab/</a>). Both platforms bring together data from many single-channel sources (e.g. a single micro-switch activated by a single running wheel) into a single computer file. Data from individual channels can then be graphed and analyzed separately at a later date.</li>
</ol>
3. Data Recordings
<ol>
	<li>Files: The above mentioned software platforms can be used to separate out single channels so that individual files are created for each running-wheel record. Such data are best visualized and graphed with specially designed programs such as Actiview (Minimitter, Bend, OR), Circadia, or Clocklab (Actimetrics, Wilmette, IL) which can all produce periodograms and actograms. However, single-channel files can also be opened and analyzed using general spreadsheet programs such as Excel (Microsoft, Redmond, WA).</li>
	<li>Calculating Circadian Time (CT): CT 12 is, by definition, the onset of running-wheel activity in nocturnal rodents. In parallel with the 24 hr day, by convention, one circadian day is broken into 24 circadian hr. Accordingly, if the circadian free-running period is 24 hr 30 min as measured by the wall clock, CT 0 will occur approximately 12 hr 15 min after CT12.</li>
</ol>

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S., Daan, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Functional+Analysis+of+Circadian+Pacemakers+in+Nocturnal+Rodents.+III.+Heavy+Water+and+Constant+Light:+Homeostasis+of+Frequency?.">A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. III. Heavy Water and Constant Light: Homeostasis of Frequency?.</a> J. Comp. Physiol. 106, 267-290 (1976).</li><li>Pittendrigh, C. S., Daan, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Functional+Analysis+of+Circadian+Pacemakers+in+Nocturnal+Rodents.+II.+The+Variability+of+Phase+Response+Curves.">A Functional Analysis of Circadian Pacemakers in Nocturnal Rodents. II. The Variability of Phase Response Curves.</a> J. Comp. Physiol. 106, 253-266 (1976).</li><li>Pittendrigh, C. 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No conflicts of interest declared.

Monitoring daily activity rhythms using running wheels is the most commonly used and reliable method for assessing the output of the master circadian clock in nocturnal rodents. Wheel-running activity, however, is only one of many aspects of behavior and physiology that can be monitored continuously. Although the vast majority of running-wheel activity occurs during the night, over 30% of the total wakefulness occurs during the daytime25,26. Other endpoints can be used to assess circadian rhythms, including ge...

<table><tbody><tr><td>Vitalview Card &amp;amp; Software</td><td>Mini Mitter</td><td>#855-0030-00</td><td>(Bend, OR, USA)</td></tr><tr><td>DP24 Dataport</td><td>Mini Mitter</td><td>#840-0024-00</td><td>(Bend, OR, USA)</td></tr><tr><td>QA4-Module </td><td>Mini Mitter</td><td>#130-0050-00</td><td>(Bend, OR, USA)</td></tr><tr><td>Magnetic Switch</td><td>Mini Mitter</td><td>#130-0015-00</td><td>(Bend, OR, USA)</td></tr><tr><td>C-50 Cable assembly</td><td>Mini Mitter</td><td>#060-0045-10</td><td>(Bend, OR, USA)</td></tr><tr><td>Rat running wheel assembly</td><td>Mini Mitter</td><td>#640-0700-00</td><td>(Bend, OR, USA)</td></tr><tr><td>Cage and tray support</td><td>Mini Mitter</td><td>#640-0400-00</td><td>(Bend, OR, USA)</td></tr><tr><td>Useable cut away cage</td><td>Mini Mitter</td><td>#664-2154-00</td><td>(Bend, OR, USA)</td></tr><tr><td>Grid floor for cage</td><td>Mini Mitter</td><td>#676-2154-00</td><td>(Bend, OR, USA)</td></tr><tr><td>Waste tray</td><td>Mini Mitter</td><td>#684-2154-00</td><td>(Bend, OR, USA)</td></tr><tr><td>Lamp housing</td><td>Microlites Scientific</td><td>#R-101</td><td>(Toronto, ON, Canada)</td></tr><tr><td>4W Fluorescent lamps</td><td>Microlites Scientific</td><td>#F4T5/CW</td><td>(Toronto, ON, Canada)</td></tr><tr><td>Isolation chambers</td><td>Custom built</td><td></td><td>28&quot;H x 20&quot;W x 28&quot;D &amp;#189;&quot; Black Melamine.</td></tr></tbody></table>

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

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, including rats, hamsters, and mice, are active during the night and relatively inactive during the day. Many other behavioral and physiological measures also exhibit daily rhythms, but in rodents, running-wheel activity serves as a particularly reliable and convenient measure of the output of the master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus. In general, through a process called entrainment, the daily pattern of running-wheel activity will naturally align with the environmental light-dark cycle (LD cycle; e.g. 12 hr-light:12 hr-dark). However circadian rhythms are endogenously generated patterns in behavior that exhibit a ~24 hr period, and persist in constant darkness. Thus, in the absence of an LD cycle, the recording and analysis of running-wheel activity can be used to determine the subjective time-of-day. Because these rhythms are directed by the circadian clock the subjective time-of-day is referred to as the circadian time (CT). In contrast, when an LD cycle is present, the time-of-day that is determined by the environmental LD cycle is called the zeitgeber time (ZT).
Although circadian rhythms in running-wheel activity are typically linked to the SCN clock6-8, circadian oscillators in many other regions of the brain and body9-14 could also be involved in the regulation of daily activity rhythms. For instance, daily rhythms in food-anticipatory activity do not require the SCN15,16 and instead, are correlated with changes in the activity of extra-SCN oscillators17-20. Thus, running-wheel activity recordings can provide important behavioral information not only about the output of the master SCN clock, but also on the activity of extra-SCN oscillators. Below we describe the equipment and methods used to record, analyze and display circadian locomotor activity rhythms in laboratory rodents.

<ol>
	<li>Computer programs: Specialized computer programs are typically used in the generation of actograms and the calculation of circadian period. These programs include, but are not limited to, Actiview (Minimitter, Bend, OR) and Circadia.</li>
	<li>Actograms: Actograms provide a graphic illustration of the daily patterns of running-wheel activity. There are single-plotted (x-axis = 24 hr) and double-plotted (x-axis = 48 hr) actograms. Both methods plot sequential days from top to bottom, but double-plott...

Watch this Scientific Journal Video about Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents at JoVE.com

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

Circadian rhythms in voluntary wheel-running activity in mammals are tightly coupled to the molecular oscillations of a master clock in the brain. As such, these daily rhythms in behavior can be used to study the influence of genetic, pharmacological, and environmental factors on the functioning of this circadian clock.

Kemirgenler Faaliyet teker Running kayıt ve Sirkadiyen Rhythms Analizi

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, ...

recording-analysis-circadian-rhythms-running-wheel-activity

Universidad de Cartagena UDEC

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Neuroscience

21.2K Görüntüleme.  McGill University. Circadian rhythms in voluntary wheel-running activity in mammals are tightly coupled to the molecular oscillations of a master clock in the brain. As such, these daily rhythms in behavior can be used to study the influence of genetic, pharmacological, and environmental factors on the functioning of this circadian clock.

Video: 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.

Sirkadiyen Rhythms Eğitim ve Parametreler Uyku Lokomotor Aktivitesi Assaying Drosophila</em

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

Nörobilim

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.

Kemirgenler Zorla Egzersiz Uyum Başlarken: Eleştirel Bir Standart Yaşlanma ile ilgili Bozukluklar ve Hastalığında Egzersiz Impact değerlendirin

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

Davranış

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.

Tekerlek Koşu Aktivitesi kullanarak Fare Sirkadiyen ve Akut Işık Yanıtları Ölçüm

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.

Faaliyet tabanlı Anoreksiya Kemirgen Modeli Kullanılarak Anoreksiya Nervoza nörobiyolojik temellerinin Eğitim için

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.

Geliştirilmiş Rat Eğitim Performans Yenilikçi Running Tekerlek tabanlı Mekanizma

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.

Uyku süresi Rodents noninvaziv, yüksek üretilen iş belirlenmesi

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.

Farelerde Egzersiz Kapasitesi ve Kardiyak Uyum Kimyasal kaynaklı Yumurtalık Yetmezliği Etkisi Eğitim için Bir Yöntem

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

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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.

Farelerde Aritmileri Tespit Etmek için Uzun Süreli Elektrokardiyografi Kayıtlarının Analizi

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 ...