A Novel Continuously Recording Approach for Unraveling Ontogenetic Development of Sleep-Wake Cycle in Rats

Abstract

Sleep-wake development in postnatal rodent life could reflect the brain maturational stages. As the altricial rodents, rats are born in a very undeveloped state. Continuous sleep recording is necessary to study the sleep-wake cycle profiles. However, it is difficult to realize in infant rats since they rely on periodic feeding before weaning and constant warming and appropriate EEG electrodes. We developed a new approach including two types of EEG electrodes and milk-feeding system and temperature-controlled incubator to make continuously polysomnographic (PSG) recording possible. The results showed that there was no evident difference in weight gaining and behaviors between pups fed through the milk-feeding system and warmed with temperature-controlled incubator and those kept with their dam. Evolutional profiles of EEG and electromyogram (EMG) activities across sleep-wake states were achieved perfectly during dark and light period from postnatal day (P) 11 to P75 rats. The ontogenetic features of sleep-wake states displayed that the proportion of rapid eye movement (REM) was 57.0 ± 2.4% and 59.7 ± 1.7% and non-REM (NREM) sleep was 5.2 ± 0.8% and 4.9 ± 0.5% respectively, in dark and light phase at P11, and then REM sleep progressively decreased and NREM sleep increased with age. At P75, REM sleep in dark and light phase respectively, reduced to 6.3 ± 0.6% and 6.9 ± 0.5%, while NREM correspondingly increased to 37.5 ± 2.1% and 58.4 ± 1.7%. Wakefulness from P11 to P75 in dark phase increased from 37.8 ± 2.2% to 56.2 ± 2.6%, but the change in light phase was not obvious. P20 pups began to sleep more in light phase than in dark phase. The episode number of vigilance states progressively decreased with age, while the mean duration of that significantly increased. EEG power spectra in 0.5–4 Hz increased with age accompanied with prolonged duration of cortical slow wave activity. Results also indicated that the dramatic changes of sleep-wake cycle mainly occurred in the first month after birth. The novel approaches used in our study are reliable and valid for continuous PSG recording for infant rats and unravel the ontogenetic features of sleep-wake cycle.

Rapid Eye Movement Sleep during Early Life: A Comprehensive Narrative Review

“…Next, an assessment of the proportions of REM sleep in various age periods demonstrated remarkably similar findings in humans [ 9 , 10 , 11 , 12 , 13 ] and animals [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], i.e., a higher percentage of REM sleep in neonates than in adults. In other words, across species, REM sleep during the early development of life (in this paper, we defined early life in humans, rats, and cats as 38 gestational weeks (GW) to 2 years, postnatal day 0 (P0) to P30, and P0 to P45, respectively) is remarkably abundant.…”

“…More recently, the REM sleep regulatory concept has been evaluated and several hypothalamic and forebrain networks including newly identified neuropeptides such as orexin and melanin-concentrating hormone (MCH) have been involved, both in the control and final expression of this behavioral state [ 6 , 27 , 154 , 155 , 156 , 157 , 158 , 159 , 160 ]. One of the most obvious correlations has been that when the human or animal brain at birth is less mature, the greater time spent in REM sleep in early postnatal life, such as REM sleep directly succeeding waking at sleep onset, is often observed in newborn humans [ 12 , 46 , 73 ] and mammals [ 16 , 18 , 20 , 22 , 23 , 138 , 152 , 161 , 162 , 163 ].…”

“…During REM sleep, brainstem circuits actively suppress motor neurons in the spinal cord to keep skeletal muscle atonia [ 6 , 154 , 155 , 157 , 178 ]. Conversely, a marked amount of twitching and gross body movement is observed during REM sleep but not during NREM sleep during the early development of humans [ 12 , 13 , 34 , 35 , 38 , 52 , 53 ] and Mammalia [ 16 , 18 , 20 , 29 , 30 , 163 , 179 , 180 ]. This distinguished pattern of REM sleep in early life suggests that the inhibiting mechanisms of spinal cord motor neurons wired with the brainstem circuits are immature.…”

Early life sleep disruption alters glutamate and dendritic spines in prefrontal cortex and impairs cognitive flexibility in prairie voles

“…In both humans and rodents, REM sleep time is especially high early in life comprising nearly 50% of all sleep. An age-related reduction in REM, typically occurring at ~2 years old in humans ( Roffwarg et al, 1966 ) and approximately 14–21 days old in rodents ( Cui et al, 2019 ; Frank and Heller, 1997 ; Rensing et al, 2018 ) may indicate a shift in the function of REM sleep from synaptic reorganization to neural repair that is conserved across species ( Cao et al, 2020 ).…”

Effects of Alcohol Extracts From Ganoderma resinaceum on Sleep in Mice Using Combined Transcriptome and Metabolome Analysis

“…Rodent models have widely been used for sleep experiments due to the high similarity of brain circuitry and electrophysiological rhythms between rodents and human. In particular, both rodents and infants exhibit a short sleep-wake cycle (38). Experimental mice share the same genetic background, and can be manipulated easily, reproducibly and reliably.…”