High-Throughput Monitoring of Sleep States in Mice Using a Novel Piezoelectric System

P.I.s:  Bruce F. O'Hara PhD, H. Craig Heller PhD, Dennis A. Grahn PhD, Paul Franken PhD.

Laboratory:  Sleep and Circadian Physiology Laboratory

Location:

Dept. of Biological Sciences
Stanford University
Stanford, CA 94305-5020

Description:  We are developing a high throughput system to monitor arousal state in rodents (especially mice). Arousal states are a fundamental aspect of global nervous system function and yet measures of sleep and wake are rarely performed in genetically altered mice due to the difficulty of EEG/EMG analysis. Such analyses requires extensive surgery, recovery, attached wires during experiments, and extensive analysis of the resulting EEG patterns. We propose a substantially simpler alternative. We have established that sleep/wake cycles in small rodents can be accurately monitored by recording respiration with a simple piezoelectric transducer attached to the floor upon which the animal rests. Distension of the floor by respiratory or other movements produces an electrical signal that can be used to distinguish sleep states. Slow wave sleep (SWS) is characterized by a regular rhythmic breathing pattern with relatively constant interbreath intervals. In REM sleep there is a large increase in respiratory variability. During wake, gross motor activities generally produce very large signals even when movements are slight. Other investigators have also found respiratory patterns to be good predictors of arousal state using somewhat similar technology (Thoman and Tynan 1979; Erkinjuntti et al. 1984; Carroll et al. 1993).

Example:  See our website for representative recordings.

Screening Protocol:  Our standard protocol calls for adaptation to the piezo chamber for two days followed by one day of baseline recording to determine normal sleep patterns. Day four is begun with six hours of sleep deprivation followed by 18 hours of recovery. A fifth day of recording will also typically be done. Our technology is still under development, and we expect to be up and running in approximately one year.

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Selected References:

1. Carroll, D.A., Denenberg, V.H., Thoman E.B. (1993) Reliability and validity of computer scoring of behavioral sleep-wake states in rats and rabbits. Physiol. Behav. 54:269-273.

2. Erkinjuntti, M., Vaahtoranta, K., Alihanka, J., Kero, P. (1984) Use of the SCSB method for monitoring of respiration, body movements and ballistocardiogram in infants. Early Human Development 9:119-126.

>3. Franken, P., Malafosse, A., Tafti, M. (1998) Genetic variation in EEG activity during sleep in inbred mice. Am. J. Physiol. 275:R1127-R1137.

4. Franken, P., Malafosse, A., Tafti, M. (1999) Genetic determinants of sleep, sleep regulation, and EEG in mice. Sleep 22: 155-169.

5. O'Hara B.F., Mignot, E. (2000) Genetics of sleep and its disorders. In: Genetic Influences on Neural and Behavioral Functions. D.W. Pfaff, W.H. Berretinni, T.H. Joh, S.C. Maxson (Eds.), CRC Press, Inc., Boca Raton, FL, pp. 307-325.

6. Tafti, M., Chollet, D., Valatx, J.-L., Franken. P, (1999) QTL approach to the genetics of sleep in recombinant inbred mice. J. Sleep Res. 8:37-43.

7. Tafti, M., Franken, P., Kitahama, K., Malafosse, A., Jouvet, M., Valatx, J.-L. (1997) Localization of candidate genomic regions influencing paradoxical sleep in mice. NeuroReport 8:3755-3758.

8. Thoman, E.B., Tynan, D. (1979) Sleep states and wakefulness in human infants: Profiles from motility monitoring. Physiol. Behav. 23:519-525.