Abstract
Drowsiness is an awake state with increased sleep drive, yet the neural correlates and underlying mechanisms remains unclear. Here, we established a mouse model of drowsiness, where mice are fasted for 1 day and then allowed to overeat high-fat food (to promote sleep) while positioned in an open-field box (to promote vigilance). They fall into a long-lasting drowsy state, as reflected by repeated and open-eyed nodding of the head while in a standing position. Simultaneous recording of electroencephalogram (EEG) and neck electromyogram (EMG) readouts revealed that this drowsy state including nodding state had multiple stages in terms of the relationship between the level of vigilance and head movement: delta oscillations decreased in power prior to the head-nodding period and increased during the non-nodding period. Cav3.1-knockout mice, which have reduced delta oscillations, showed frequent head nodding with reduced duration of nodding episodes compared to wild-type mice. This suggests that the balance of drive is tilted in favor of wakefulness, likely due to their previously proposed decrease in sleep-promoting functions. Our findings indicate that delta oscillations play a dominant role in controlling vigilance dynamics during sleep/wake competition and that our novel mouse model may be useful for studying drowsiness and related neurological disorders.
Highlights
In the drowsy state, sleep and wake drives coexist to allow animals to maintain a minimal vigilance that can allow them to avoid potential risks, such as predatory attacks [1, 2]
On day-3, mice were divided into three groups and given either no food (N), 1.5 g of normal food (NR) or high fat food (HF) (Fig. 1a)
Here, we established a behavioral paradigm for inducing a long-lasting drowsiness characterized by frequent nodding behaviors (Fig. 1)
Summary
Sleep and wake drives coexist to allow animals to maintain a minimal vigilance that can allow them to avoid potential risks, such as predatory attacks [1, 2]. It has proven challenging to study the mechanisms underlying sleep/wake competition in the drowsy state, largely because: 1) drowsiness occurs intermittently with short latency, meaning that there is only a limited time for mechanistic observation; and 2) due to stress, animals remain vigilant in experimental test boxes even during their normal sleep cycle. Identifying the role of T-type Ca2+ channels during the waking state has been challenging because thalamic burst firing is rarely observed during wakefulness [12]. To address this issue, we first tried to establish
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