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Examples of (a) PS for sleep signals of Fig. 1,(b) PS for wake signals of Fig. 2,(c) AC for sleep signals of Fig. 1,(d) AC for wake signals of Fig. 2,(e) CA for sleep signals of Fig. 1,(f) CA for wake signals of Fig. 2.
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This work presents a non-invasive high-throughput system for automatically detecting characteristic behaviours in mice over extended periods of time, useful for phenotyping experiments. The system classifies time intervals on the order of 2 to 4 seconds as corresponding to motions consistent with either active wake or inactivity associated with sle...
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Citations
... The PiezoSleep motion sensor-based system scores sleep with over 90% accuracy as verified by human observation and simultaneous EEG recordings in different strains of mice 23,24,31 . We first sought to validate the PiezoSleep system, which is a more recent variation of the technology, to make sure it would be accurate for the specific Cln3KO and WT mice to be used in the large cohort study. ...
The neuronal ceroid lipofuscinoses (NCLs) are a group of recessively inherited neurodegenerative diseases characterized by lysosomal storage of fluorescent materials. CLN3 disease, or juvenile Batten disease, is the most common NCL that is caused by mutations in the Ceroid Lipofuscinosis, Neuronal 3 (CLN3) gene. Sleep disturbances are among the most common symptoms associated with CLN3 disease, yet this is understudied and has not been delineated in an animal model of the disease. The current study utilized a non-invasive, automated piezoelectric motion sensing system (PiezoSleep) to classify sleep and wakefulness in a Cln3Dex1-6/Dex1-6 (Cln3KO) mouse model and age- and sex-matched wild-type (WT) controls. The sleep-wake classification by PiezoSleep was found to be about 90% accurate when validated against simultaneous gold standard polysomnographic recordings including electroencephalography (EEG) and electromyography (EMG) in a small cohort of WT and Cln3KO mice. Our large cohort PiezoSleep study reveals sleep abnormalities during the light period (LP) in male Cln3KO mice compared to WT male, and more subtle differences in Cln3KO female mice throughout the dark period (DP) compared to WT female, recapitulating sleep abnormalities seen in CLN3 disease patients. Our characterization of sleep in a mouse model of CLN3 disease contributes to a better understanding of the sleep disturbances commonly reported for CLN3 disease and other NCLs, which will facilitate the development of new disease treatment and management strategies.
... Custom-molded piezoelectric sensors were used to measure mouse sleep 1-30 DPI (Signal Solutions LLC, Lexington, KY). Previous iterations of these sensors have been demonstrated to classify sleep behavior based on physiological parameters and have been validated against EEG and human observations with >90% accuracy (Donohue et al., 2008). Mice were introduced to the cages immediately following injury and were left undisturbed except for daily wellness checks. ...
... Piezoelectric signals were analyzed over 8 s epochs and decision statistics were calculated utilizing regular amplitude signals recorded during the epoch. Regular beathing at 2-4 Hz was classified as sleep-behavior which was differentiated from quiet and active wake at higher frequencies (Donohue et al., 2008). Percent-sleep data were exported in bins of 1 h to allow for averaging of discrete time periods. ...
Traumatic brain injury (TBI) causes a prolonged inflammatory response in the central nervous system (CNS) driven by microglia. Microglial reactivity is exacerbated by stress, which often provokes sleep disturbances. We have previously shown that sleep fragmentation (SF) stress after experimental TBI increases microglial reactivity and impairs hippocampal function 30 days post-injury (DPI). The neuroimmune response is highly dynamic the first few weeks after TBI, which is also when injury induced sleep-wake deficits are detected. Therefore, we hypothesized that even a few weeks of TBI SF stress would synergize with injury induced sleep-wake deficits to promote neuroinflammation and impair outcome. Here, we investigated the effects of environmental SF in a lateral fluid percussion model of mouse TBI. Half of the mice were undisturbed, and half were exposed to 5 h of SF around the onset of the light cycle, daily, for 14 days. All mice were then undisturbed 15–30 DPI, providing a period for SF stress recovery (SF-R). Mice exposed to SF stress slept more than those in control housing 7–14 DPI and engaged in more total daily sleep bouts during the dark period. However, SF stress did not exacerbate post-TBI sleep deficits. Testing in the Morris water maze revealed sex dependent differences in spatial reference memory 9–14 DPI with males performing worse than females. Post-TBI SF stress suppressed neurogenesis-related gene expression and increased inflammatory signaling in the cortex at 14 DPI. No differences in sleep behavior were detected between groups during the SF stress recovery period 15–30 DPI. Microscopy revealed cortical and hippocampal IBA1 and CD68 percent-area increased in TBI SF-R mice 30 DPI. Additionally, neuroinflammatory gene expression was increased, and synaptogenesis-related gene expression was suppressed in TBI-SF mice 30 DPI. Finally, IPA canonical pathway analysis showed post-TBI SF impaired and delayed activation of synapse-related pathways between 14 and 30 DPI. These data show that transient SF stress after TBI impairs recovery and conveys long-lasting impacts on neuroimmune function independent of continuous sleep deficits. Together, these finding support that even limited exposure to post-TBI SF stress can have lasting impacts on cognitive recovery and regulation of the immune response to trauma.
... The non-invasive piezo sleep cage system (Signal Solutions, Lexington, KY) used in this study consisted of 16 individual units that simultaneously monitor sleep and wake states, as previously published. 25 This system allows for longitudinal sleep/wake monitoring with greater throughput than electroencephalography/ electromyography. PiezoSleep can assess total, day, and night sleep and wake durations, number of sleep bouts, and sleep bout length. ...
Chronic sleep/wake disturbances (SWDs) are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong SWDs. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in 4-month-old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. Sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at 3 months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Further, TBI mice showed extensive brain tissue loss and increased glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 levels in the hypothalamus and vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes post-TBI early in life.
... Throughout the experiment, we characterized patterns of sleep vs. activity using a non-invasive Piezo Sleep Sensor System (Donohue et al. 2008;Signal Solutions LLC, Mang et al. 2014;Yaghouby et al. 2016). This system involves placing a thin dielectric or "piezoelectric" sheet under the animal's slip cage. ...
Seasonal affective disorder (SAD) is a recurrent depression triggered by exposure to short photoperiods, with a subset of patients reporting hypersomnia, increased appetite, and carbohydrate craving. Dysfunction of the microbiota - gut - brain axis is frequently associated with depressive disorders, but its role in SAD is unknown. Nile grass rats (Arvicanthis niloticus) are potentially useful for exploring the pathophysiology of SAD, as they are diurnal and have been found to exhibit anhedonia and affective-like behavior in response to short photoperiods. Further, given grass rats have been found to spontaneously develop metabolic syndrome, they may be particularly susceptible to environmental triggers of metabolic dysbiosis. We conducted a 2 × 2 factorial design experiment to test the effects of short photoperiod (4 h:20 h Light:Dark (LD) vs. neutral 12:12 LD), access to a high concentration (8%) sucrose solution, and the interaction between the two, on activity, sleep, liver steatosis, and the gut microbiome of grass rats. We found that animals on short photoperiods maintained robust diel rhythms and similar subjective day lengths as controls in neutral photoperiods but showed disrupted activity and sleep patterns (i.e. a return to sleep after an initial bout of activity that occurs ~ 13 h before lights off). We found no evidence that photoperiod influenced sucrose consumption. By the end of the experiment, some grass rats were overweight and exhibited signs of non-alcoholic fatty liver disease (NAFLD) with micro- and macro-steatosis. However, neither photoperiod nor access to sucrose solution significantly affected the degree of liver steatosis. The gut microbiome of grass rats varied substantially among individuals, but most variation was attributable to parental effects and the microbiome was unaffected by photoperiod or access to sucrose. Our study indicates short photoperiod leads to disrupted activity and sleep in grass rats but does not impact sucrose consumption or exacerbate metabolic dysbiosis and NAFLD.
... The non-invasive piezo sleep cage system (Signal Solutions, Lexington, KY) used in this study consisted of 16 individual units which simultaneously monitor sleep and wake states, as previously published. 26 This system allows for longitudinal sleep/wake monitoring with greater throughput than EEG/EMG. PiezoSleep can assess total, day, and night sleep and wake durations, number of sleep bouts, and sleep bout length. ...
Chronic sleep/wake disturbances are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong sleep/wake disturbances. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in four months old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. The sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at three months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Furthermore, TBI mice showed extensive brain tissue loss and increased GFAP and IBA1 levels in the hypothalamus and the vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes following TBI early in life.
... Sleep/wake activity was monitored using a validated, computerized piezoelectric system (PiezoSleep; Signal Solutions, Lexington, KY, USA). This noninvasive system, automatically scores sleep and waking states in mice (SleepStat; Signal Solutions, Lexington, KY, USA) [58,[102][103][104][105][106]. Briefly, a piezoelectric film able to detect pressure variations is placed under the cage floor. ...
Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). In murine models, chronic SF can impair endothelial function and induce cognitive declines. These deficits are likely mediated, at least in part, by alterations in Blood–brain barrier (BBB) integrity. Male C57Bl/6J mice were randomly assigned to SF or sleep control (SC) conditions for 4 or 9 weeks and in a subset 2 or 6 weeks of normal sleep recovery. The presence of inflammation and microglia activation were evaluated. Explicit memory function was assessed with the novel object recognition (NOR) test, while BBB permeability was determined by systemic dextran-4kDA-FITC injection and Claudin 5 expression. SF exposures resulted in decreased NOR performance and in increased inflammatory markers and microglial activation, as well as enhanced BBB permeability. Explicit memory and BBB permeability were significantly associated. BBB permeability remained elevated after 2 weeks of sleep recovery (p < 0.01) and returned to baseline values only after 6 weeks. Chronic SF exposures mimicking the fragmentation of sleep that characterizes patients with OSA elicits evidence of inflammation in brain regions and explicit memory impairments in mice. Similarly, SF is also associated with increased BBB permeability, the magnitude of which is closely associated with cognitive functional losses. Despite the normalization of sleep patterns, BBB functional recovery is a protracted process that merits further investigation.
... Sleep and wake states were determined using a non-invasive, piezoelectric system (Signal Solutions, LLC, Lexington, KY, USA). The piezoelectric system has been described in detail in previous publications (58,59). Briefly, it is comprised of a plexiglass cage with a piezoelectric sensor film lining the bottom that detects pressure underneath fresh bedding. ...
Alzheimer's disease (AD) is the most common cause of dementia. The APOE-ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD. APOE genotype modulates the effect of sleep disruption on AD risk, suggesting a possible link between apoE and sleep in AD pathogenesis which is relatively unexplored. We hypothesized that apoE modifies Aβ deposition and Aβ plaque-associated tau seeding and spreading in the form of neuritic plaque (NP)-tau pathology in response to chronic sleep deprivation (SD) in an apoE isoform-dependent fashion. To test this hypothesis, we used APPPS1 mice expressing human APOE-ε3 or -ε4 with or without AD-tau injection. We found that SD in APPPS1 mice significantly increased Aβ deposition and peri-plaque NP-tau pathology in the presence of APOE4, but not APOE3. SD in APPPS1 mice significantly decreased microglial clustering around plaques and aquaporin-4 (AQP4) polarization around blood vessels in the presence of APOE4 but not APOE3. We also found that sleep deprived APPPS1:E4 mice injected with AD tau had significantly altered sleep behaviors as compared to APPPS1:E3 mice. These findings suggest that APOE-ε4 genotype is a critical modifier in the development of AD pathology in response to SD.
... A typical sleep pattern consists of only very regular, but minuscule waves with an amplitude between 2 and 4 Hz due to the mere detected chest movement coming from the breathing of the sleeping mouse. Piezoelectric recordings do not allow for differentiation of sleep stages, but its classification accuracy of >90% to discriminate between sleep and wake has been validated with EEG [28,38,39]. ...
The sleep–wake cycle is a highly regulated behavior in which a circadian clock times sleep and waking, whereas a homeostatic process controls sleep need. Both the clock and the sleep homeostat interact, but to what extent they influence each other is not understood. There is evidence that clock genes, in particular Period2 (Per2), might be implicated in the sleep homeostatic process. Sleep regulation depends also on the proper functioning of neurons and astroglial cells, two cell-types in the brain that are metabolically dependent on each other. In order to investigate clock-driven contributions to sleep regulation we non-invasively measured sleep of mice that lack the Per2 gene either in astroglia, neurons, or all body cells. We observed that mice lacking Per2 in all body cells (Per2Brdm and TPer2 animals) display earlier onset of sleep after sleep deprivation (SD), whereas neuronal and astroglial Per2 knock-out animals (NPer2 and GPer2, respectively) were normal in that respect. It appears that systemic (whole body) Per2 expression is important for physiological sleep architecture expressed by number and length of sleep bouts, whereas neuronal and astroglial Per2 weakly impacts night-time sleep amount. Our results suggest that Per2 contributes to the timing of the regulatory homeostatic sleep response by delaying sleep onset after SD and attenuating the early night rebound response.
... To test this hypothesis, male and female grass rats housed in winter-like dim light condition during the day received 1-hour early morning BLT using full-spectrum white light (simulated daylight) of 10,000 lx daily for 4 weeks, while the control group received daily 1hour narrowband red light. Sleep/wakefulness was monitored during the 4th week of treatment using a piezoelectric system, which detects pressure changes associated with breathing and movement (Donohue et al., 2008;Yaghouby et al., 2016). In-cage locomotor activity was recorded in the females throughout the 4 weeks. ...
... This detection method is noninvasive and achieves >90 % accuracy for sleep/wake classification based on validation with simultaneous recording through EEG/EMG (Mang et al., 2014). Piezo signals were acquired in the same manner as previous studies have described (Donohue et al., 2008;Mang et al., 2014;Yaghouby et al., 2016). These signal outputs were converted into Feat-Vec files (FeatVecMaker, Signal Solutions version 2.08218) and analyzed using SleepStats (Signal Solutions, version 2.28). ...
Background:
Bright light therapy (BLT) is the first-line treatment for seasonal affective disorder. However, the neural mechanisms underlying BLT are unclear. To begin filling this gap, the present study examined the impact of BLT on sleep/wakefulness, daily rhythms, and the wakefulness-promoting orexin/hypocretin system in a diurnal rodent, Nile grass rats (Arvicanthis niloticus).
Methods:
Male and female grass rats were housed under a 12:12 h light/dark cycle with dim light (50 lx) during the day. The experimental group received daily 1-h early morning BLT (full-spectrum white light, 10,000 lx), while the control group received narrowband red light for 4 weeks. Sleep/wakefulness and in-cage locomotor activity were monitored, followed by examination of hypothalamic prepro-orexin and orexin receptors OX1R and OX2R expression in corticolimbic brain regions.
Results:
The BLT group had higher wakefulness during light treatment, better nighttime sleep quality, and improved daily rhythm entrainment compared to controls. The impact of BLT on the orexin system was sex- and brain region-specific, with males showing higher OX1R and OX2R in the CA1, while females showed higher prepro-orexin but lower OX1R and OX2R in the BLA, compared to same-sex controls.
Limitations:
The present study focused on the orexin system in a limited number of brain regions at a single time point. Sex wasn't a statistical factor, as male and female cohorts were run independently.
Conclusions:
The diurnal grass rats show similar behavioral responses to BLT as humans, thus could be a good model for further elucidating the neural mechanisms underlying the therapeutic effects of BLT.
... Sleep/wake activity was monitored using a validated, computerized piezoelectric system (PiezoSleep; Signal Solutions, Lexington, KY)). This noninvasive system, automatically scores sleep and waking states in mice (SleepStat; Signal Solutions, Lexington, KY) [74][75][76][77][78]. Briefly, a piezoelectric film able to detect pressure variations is placed under the cage floor. ...
Obstructive sleep apnea (OSA) is a highly prevalent condition characterized by episodes of partial or complete breath cessation during sleep that induce sleep fragmentation (SF). One of the frequent manifestations of OSA is the presence of excessive daytime sleepiness (EDS) associated with cognitive deficits. Solriamfetol (SOL) and modafinil (MOD) are wake promoting agents commonly prescribed to improve wakefulness in OSA patients with EDS. This study aimed to assess the effects of SOL and MOD in a murine model of OSA characterized by periodic SF. Male C57Bl/6J mice were exposed to either control sleep (SC) or SF (mimicking OSA) during the light period (06:00h to 18:00h) for 4 weeks, which consistently induces sustained excessive sleepiness (ES) during the dark phase. Both groups were then randomly assigned to receive once-daily intraperitoneal injections of SOL (200mg/kg), MOD (200mg/kg) or vehicle (VEH) for 1 week while continuing exposures to SF or SC. Sleep/wake activity and sleep propensity were assessed during the dark phase. Novel object recognition (NOR), elevated-plus maze test (EPMT), and forced swim test (FST) were performed before and after treatment. SOL or MOD decreased sleep propensity in SF, but only SOL induced improvements in explicit memory, while MOD exhibited increased anxiety behaviors. Chronic SF, a major hallmark of OSA, induces EDS in young adult mice that is mitigated by both SOL and MOD. SOL, but not MOD, significantly improves SF-induced cognitive deficits. Increased anxiety behaviors are apparent in MOD treated mice. Further studies aiming to elucidate the beneficial cognitive effects of SOL are warranted.
