Surgery – Diagnostic testing – Detecting muscle electrical signal
Reexamination Certificate
2001-03-07
2002-11-05
Shaver, Kevin (Department: 3736)
Surgery
Diagnostic testing
Detecting muscle electrical signal
C600S544000
Reexamination Certificate
active
06477408
ABSTRACT:
BACKGROUND OF THE INVENTION
In adult animals the only way to accurately determine and characterize vigilance states (i.e. wake and the two primary stages of sleep, Rapid Eye Movement (REM) and non-Rapid Eye Movement (NREM) sleep, is to monitor electroencephalographic (EEG) and electromyographic (EMG) activity using chronic electrodes previously implanted under deep anesthesia. For studies in animals this typically requires extensive surgical procedures making it very expensive and time consuming to record EEG and EMG sleep from a large number of animals.
Neonatal sleep has been characterized both in humans and non-human mammalian species. Because EEG activity appears undifferentiated in the early postnatal period, characterization of neonatal sleep has depended on behavioral criteria. Two distinct types of behavioral sleep are scored in neonatal mammals. Active Sleep (AS) is characterized by phasic motor activity including numerous muscular twitches, REM and irregular respiration. AS has been assumed to represent an immature form of REM sleep. Quiet Sleep (QS) is behaviorally defined as periods of relative motor quiescence coupled with regular respiration and is thought to represent an immature form of NREM sleep or slow wave sleep (SWS) that appears later in the postnatal period (Jouvet-Mounier et al.,1970; Roffwarg et al., 1966). AS occupies a large proportion of sleep time in the neonate and then declines progressively with maturation. In contrast, QS initially occupies a very small portion of the neonatal sleep record and gradually increases with postnatal development.
There has been an ongoing controversy as to whether or not AS and QS in neonates are homologous to the EEG-defined REM sleep and NREM sleep, respectively in adult animals (Frank and Heller, 1997
a
). Nevertheless, AS in neonates and REM sleep in adult animals are behaviorally characterized by muscular atonia, irregular respiration and REM. Consequently, neonatal AS and REM sleep in adult mammals are often considered to be homologous sleep states. In rats, the appearance of an EEG identifiable REM sleep-like state in the second postnatal week (Jouvet- Mounier et al., 1970; Gramsbergen, 1976) is followed by the appearance of diurnal and homeostatic sleep regulatory mechanisms in the 3-4
th
postnatal weeks (Alfoldi et al., 1990; Frank and Heller, 1997
b
). In adult mammals, the sleep-wake distribution across the circadian day is regulated by an endogenous oscillator located within the hypothalamic suprachiasmatic nuclei (SCN). In the rat, endogenous SCN rhythms are first detected in the fetal period (Reppert et al., 1988) but do not couple to sleep-wake cycles until the 3
rd
postnatal week (Jouvet-Mounier et al., 1970).
Because sleep-wake states are exceedingly difficult to characterize by the EEG activity before the 9
th
day of life in rats (Jouvet-Mounier et al. 1970; Gramsbergen, 1976), the EEG and EMG recordings are often combined with registration of movements by an actograph and/or observation of behavior to determine the vigilance state, i.e. wake, AS and QS. When awake, the rat pup is almost never still. QS is characterized by motionless interrupted by startles (sudden phasic contractions of body muscles), while AS is characterized by intense twitching of the musculature.
A selective investigation on evolution of muscular twitches during the 21 postnatal days of the rat pups indicates an age-dependent progression of these twitches. (Lapointe and Nosal, 1979) During the 21 days of the pre-weaning period, the rat pups exhibit brief muscular twitches of variable intensity which occur in different body regions (head, limbs, dorsal and ventral region, tail). The muscular twitches are abundant in the first 10 days of postnatal life. Thereafter they progressively decrease until the 13
th
day and then fall abruptly until day 17. The disappearance of muscular twitches coincides with a progressive increase in more elaborated behavioral activities (e.g. motility and exploration) and with the maturity of the sense organs (eyes and ears). This evolution parallels the gradual changes taking place in the sleep-wake states during the postnatal developing rat.
Even so, it is difficult, at best, to screen a large number (upwards of thousands) of animal subjects because of the time-consuming and costly nature of recording sleep via brain electrical activity in adult animals. It is necessary to determine not only wake from sleep but also to differentiate the two primary sleep states: rapid eye movement (REM) sleep and non-REM (NREM) sleep from one another. This is a difficult task in view of the time and money it takes to perform surgery, allow for recovery and adaptation to recording conditions before collecting EEG and EMG recordings for many hours in adult animals.
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Marcos G. Frank, et al., “Effects of Sleep Deprivation in Neonatal Rats.”AJP-Regulatory, Integrative and Comparative Physiology, Jul. 1998, pp. R148-R157, vol. 275, Issue 1, The American Physiological Society.
Paul Franken, et al., “Genetic Variation in EEG Activity During Sleep in Inbred Mice.”AJP-Regulatory, Integrative and Comparative Physiology, Oct. 1998, pp. R1127-R1137, vol. 275, Issue 4, The American Physiological Society.
Daniele Jouvet-Mounier, et al., “Ontogenesis of the States of Sleep in Rat, Cat, and Guinea Pig During the First Postnatal Month.”Developmental Psychobiology, Oct. 1969, pp. 216-239, vol. 2, Issue 4, John Wiley & Sons, Inc.
Dugovic Christine
Turek Fred W.
Marmor II Charles
Northwestern University
Reinhart Boerner Van Deuren S.C.
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