Description
Introduction
The AutoSomTM system is an automated sleep-deprivation system specially designed to conduct sleep-related research in rodents. The AutoSomTM system enables non-invasive, fully automated, and highly-regulated monitoring of rodents’ sleep/wake activity. It delivers a non-painful and non-stressing stimulus to awaken the mice and allows hands-on control over the stimulus. The system employs automated sensors and a floor-pad to record sleep/wake states in the laboratory animals. The AutoSomTM system is user-friendly and an easily programmable device.
Sleep deprivation is widely used in biomedical research to assess memory, learning, and sleep-related disorders. Total sleep deprivation is a process of preventing the animal from falling asleep at all, while selective sleep deprivation is to eliminate particular sleep stages. The latter is frequently used to deprive rapid-eye-movement sleep (REM sleep) in rodents, usually by placing the animals on small platforms or pads surrounded by water. Total sleep deprivation (REM and non-REM sleep) is less demanding technically and is simply achieved by removing or introducing objects within the cages or by gently handling the rodents to keep them awake. Rats and mice are the most preferred species used for sleep research to investigate sleep architecture, sleep homeostasis, circadian rhythms, and their underlying neurochemical and molecular mechanisms. Rodents provide good genetic models, insight into the control of sleep in humans and suggest genetic influences on many aspects of behavioral state regulation.
Apparatus and Equipment
The AutoSomTM system is non-invasive as the animals are tested and monitored in their home cages having bedding, food, and water, making the system valuable to conduct experimental manipulations and sleep assessments for extended periods. The device consists of a floor-sensor board that detects the vibrations when the mouse moves in its home cage. A motor is fixed under the floor-sensor board that turns the rotating bar to keep the animal awake. The system operates four units interfacing one computer via USB cable. The screenshots of the AutoSomTM system using vibration signal are used to assess active or inactive (‘sleep’), and an infrared array is utilized for the detection of the location and locomotion of the animal.
The AutoSomTM system contains two modes: time-dependent and state-dependent.
The ‘Time-dependent’ mode allows the user to measure the total duration, interval, and start time of the automated sleep deprivation experiment. By adjusting the time-dependent mode, the user can change the wake-up time schedule.
The second mode is the ‘State-dependent’ mode, which is used for “sleep-specific” deprivation, chronic sleep restriction, and sleep “fragmentation.” It is only operational to wake up the animal when the mouse is in an inactive/sleep state. The system records electromyogram and electrocardiograph before, during, and at the end of the sleep deprivation process.
Protocol
- House the experimental animals in their home-cages with proper food and water provision under constant light/dark cycles.
- Implant the EEG and EMG electrodes in the animals for baseline recordings.
- Allow the animals to recover for 14 days after the implantation of the electrodes.
- Record baseline EEG/EMG signals 23 hours before starting the sleep deprivation.
- Deprive the animals of sleep as per the experimental requirements by placing the animals in the AutoSomTM
- Record the parameters by using the screenshots captured by the SmartCageTM
- Store the digital data for offline analysis.
Applications
Fully Automated Sleep Deprivation in Mice as a Tool in Sleep Research (Fenzl et al., 2007)
Sleep deprivation is commonly used in sleep and memory research. Manual methods like gentle handling are cumbersome, labor-intensive, and time-consuming. Unlike gentle handling, the automated sleep deprivation system is a standardized, non-invasive, and simpler toolkit to deprive animals of sleep during experiments. The system enables automated measurements and recordings of EMG and EEG signals to assess the sleep/wake activity of the animals. The system can be easily introduced into the home-cages of the animals minimizing the transport-induced stress and prolonged acclimation requirements.
Recording and Analysis of Sleep in Mice (Veasey et al., 2000)
Genetic impact on sleep control can be assessed by studying the significant differences in sleep/wake activity among inbred strains of mice. Behavioral states analysis and description are essential to understanding sleep mechanisms in animals. The AutoSomTM system is designed to investigate the baseline sleep structure and the response to sleep deprivation in mice. Measurements of sleep consolidation and fragmentation, rapid eye movement (REM) sleep latency, and delta density decline with sleep were also studied to characterize the sleep further. The automated sleep deprivation system not only helps to record baseline measurements but also minimizes stress to animals as well as the handler.
Testing Memory Deficits in Rodents (Colavito, et al., 2013)
Sleep deprivation also aids in assessing memory deficits in rodents. The study aims at understanding the impact of sleep on cognition and memory. Also, sleep deprivation can be used as a tool to evaluate the efficacy of certain drugs candidates designed to improve memory performance in rodents. The results suggested that sleep deprivation not only helps to evaluate memory but also permits investigation of the neurobiological mechanisms subservient to sleep and sleep loss.
Automated sleep deprivation system has been successful in advancing translational research by allowing comparative analysis between preclinical studies and investigations in humans: whatever role sleep and sleep loss play in cognition, such role is conserved between rodents and humans.
Strengths and Limitations
- The AutoSomTM system is a non-invasive, non-stressful, and simpler toolkit to deprive the animals of sleep for sleep and memory research.
- Sleep deprivation using the AutoSomTM system allows 99.5% suppression of non-REM and REM sleep across 6 h of deprivation.
- Automatic sleep deprivation’s and gentle handling’s corticosterone levels do not differ significantly.
- The AutoSomTM system can be easily incorporated in the home-cage of the test animals thereby minimizing the transport-related stress to the animals.
- The automated sleep deprivation system is fully standardized unlike the manual methods of sleep deprivation.
- The AutoSomTM system enables handling of up to eight animals simultaneously for extended periods making the system more valuable.
- The incorporations of an optical system that captures the screenshots of the recordings allow the researcher to analyze the behavioral states of the animals without disturbing them.
- The quality and amount of stimulation are standardized in the AutoSomTM
- The AutoSomTM system is a labor saving and highly standardized alternative to gentle handling.
Precautions
- Use adult mice in the experiments for behavioral state and sleep assays using the AutoSomTM
- Avoid much disturbance in the laboratory to minimize any noise which can be stressful to animals.
- Sanitize the AutoSomTM floor pad with 0.25% bleach before starting the procedure.
- Always change gloves before handling mice from different cages.
References
- Colavito, V., Fabene, P. F., Grassi-Zucconi, G., Pifferi, F., Lamberty, Y., Bentivoglio, M., & Bertini, G. (2013). Experimental sleep deprivation as a tool to test memory deficits in rodents. Front Syst Neurosci, 7(106).
- Fenzl, T., Romanowski, C. P., Flachskamm, C., Honsberg, K., Boll, E., Hoehne, A., & Kimura, M. (2007). Fully automated sleep deprivation in mice as a tool in sleep research. Journal of Neuroscience Methods, 166, 229-235.
- Veasey, S. C., Valladares, O., Fenik, P., Kapfhamer, D., Sanford, L., Benington, J., & Bucan, M. (2000). An Automated System for Recording and Analysis of Sleep in Mice. Sleep, 23(8).
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