Circadian desynchronization of core body temperature and sleep stages in the rat

Abstract

Proper functioning of the human circadian timing system is crucial to physical and mental health. Much of what we know about this system is based on experimental protocols that induce the desynchronization of behavioral and physiological rhythms within individual subjects, but the neural (or extraneural) substrates for such desynchronization are unknown. We have developed an animal model of human internal desynchrony in which rats are exposed to artificially short (22-h) light-dark cycles. Under these conditions, locomotor activity, sleep-wake, and slow-wave sleep (SWS) exhibit two rhythms within individual animals, one entrained to the 22-h light-dark cycle and the other free-running with a period >24 h ( >24 h). Whereas core body temperature showed two rhythms as well, further analysis indicates this variable oscillates more according to the >24 h rhythm than to the 22-h rhythm, and that this oscillation is due to an activity-independent circadian regulation. Paradoxical sleep (PS), on the other hand, shows only one freerunning rhythm. Our results show that, similarly to humans, (i) circadian rhythms can be internally dissociated in a controlled and predictable manner in the rat and (ii) the circadian rhythms of sleep-wake and SWS can be desynchronized from the rhythms of PS and core body temperature within individual animals. This model now allows for a deeper understanding of the human timekeeping mechanism, for testing potential therapies for circadian dysrhythmias, and for studying the biology of PS and SWS states in a neurologically intact model.

Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation

“…In support of this view, we have previously shown that desynchrony of sleep stages in the forced desynchronized rat emerges from the desynchrony of specific neuronal subpopulations within the SCN. 8,9 Our current findings indicate that the local circadian misalignment of neurons within the SCN circuitry, through the desynchrony of sleep stages, may impair higher cognitive functions such as long-term hippocampus memory consolidation.…”

“…Analysis of ECoG sleep recordings in these animals reveals that whereas NREM sleep is temporally organized according to both periodicities, REMS only exhibits a ~25-h rhythm. 8,9 The different rhythmicity of each sleep stage leads to a cycle that alternates between days in which sleep architecture (the temporal distribution of NREM and REM sleep) is similar to that of LD24 rats (aligned days, Figure 2C and 2D), and days in which wakefulness does not occur primarily during the dark phase and REM predominates in the dark phase (misaligned days, Figure 2E and 2F).…”

“…However, forced desynchronized rats show desynchrony in other circadian rhythms that could be responsible for memory deficits. 5,9,15,16 To determine whether memory deficits in LD22 misaligned animals are associated specifically with our observed fragmentation of NREM and REM sleep, we repeated our contextual fear conditioning experiments in all three experimental groups while simultaneously recording the vigilance states with ECoG electrodes after training for each animal. We plotted a survival curve and fitted an exponential decay curve for each animal and sleep stage during the light phase one day after training.…”

“…[8][9][10] We tested whether this abnormal timing of sleep stages leads to deficits in total sleep or in specific sleep stages. We calculated the percent of sleep throughout: (1) a 24-h period in LD24-housed animals, (2) a 22-h period in LD22-housed animals during aligned phases, or (3) a 22-h period in LD22-housed animals during misaligned phases.…”

Complexity of theNeurospora crassaCircadian Clock System: Multiple Loops and Oscillators

“…Several lines of evidence point toward the existence of multiple distinct oscillators in cells and/or tissues of organisms contributing to circadian timing. First, there exist free-running rhythms with different period lengths in the same organism (Morse et al 1994;Sai and Johnson 1999;Cambras et al 2007), and there is residual rhythmicity in strains that are defective in known oscillator components (Loros et al 1986;Stanewsky et al 1998;Emery et al 2000;Collins et al 2005). Second, some tissue-specific oscillators are constructed differently from the core oscillators located in the brain (Stanewsky et al 1998;Ivanchenko et al 2001;Krishnan et al 2001;Hardin et al 2003;Collins et al 2005).…”