Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset

Sato, Masatoshi; Sagawa, Yohei; Hirai, Nobuhide; Sato, Shinichi; Okuro, Masashi; Kumar, Samika; Kanbayashi, Takashi; Shimizu, Tetsuo; Sakai, Noriaki; Nishino, Seiji

doi:10.1016/j.expneurol.2014.08.004

Cited by 6 publications

(9 citation statements)

References 13 publications

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“…Though mouse sleep can be measured using other noninvasive approaches, EF sensor recordings have the additional ability to simultaneously quantify other motor behaviors such as ventilation profiles in non-REM and REM sleep, grooming, locomotion, eating, and drinking using only a frequency-based features of a single voltage channel. 31 Other noninvasive movement-based methods to measure rodent sleep have been reported using video, [18][19][20]22,43 whole body plethysmography, 7,11 infrared beams, 19,44 pulse Doppler radar, 21 piezoelectric films, 10,24,[45][46][47] and actimetry. 48,49 Several of these approaches, namely video, infrared beams, and actimetry, cannot distinguish non-REM from REM sleep 18,19,22,[43][44][45][46][47][48][49] limiting their applications to when only sleep/wake discrimination is sufficient.…”

Section: Discussionmentioning

confidence: 99%

“…31 Other noninvasive movement-based methods to measure rodent sleep have been reported using video, [18][19][20]22,43 whole body plethysmography, 7,11 infrared beams, 19,44 pulse Doppler radar, 21 piezoelectric films, 10,24,[45][46][47] and actimetry. 48,49 Several of these approaches, namely video, infrared beams, and actimetry, cannot distinguish non-REM from REM sleep 18,19,22,[43][44][45][46][47][48][49] limiting their applications to when only sleep/wake discrimination is sufficient. Of the published studies capable of noninvasively measuring 3state sleep architecture, the reported overall accuracies to EEG/EMG range from 84% to 91%, 10,11,20,21,24 .…”

Section: Discussionmentioning

confidence: 99%

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Noninvasive three-state sleep-wake staging in mice using electric field sensors

Kloefkorn

Aiani

Lakhani

et al. 2020

Journal of Neuroscience Methods

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Study Objective: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors.Methods: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were attached to the exterior of each chamber to record respiration and other movement simultaneously with EEG, EMG, and video. A sleep-wake scoring method based on EF sensor data was developed with reference to EEG/EMG and then validated by three expert scorers. Additionally, novice scorers without sleep-wake scoring experience were self-trained to score sleep using only the EF sensor data, and results were compared to those from expert scorers. Lastly, ability to capture three-state sleep-wake staging with EF sensors attached to traditional mouse home-cages was tested.Results: EF sensors quantified wake, rapid eye movement (REM) sleep, and non-REM sleep with high agreement (>93%) and comparable inter-and intra-scorer error as EEG/EMG. Novice scorers successfully learned sleep-wake scoring using only EF sensor data and scoring criteria, and *

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Noninvasive three-state sleep-wake staging in mice using electric field sensors

Kloefkorn

Aiani

Lakhani

et al. 2020

Journal of Neuroscience Methods

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“…Currently, there is no prescreening method prior to EEG/EMG studies for sorting mice that are highly symptomatic for narcolepsy. In a previous study, Atax mice were monitored with piezoelectric detection of movement and heartrate for a few hours during the light period, but the algorithm for autoscoring was only 73% accurate against manual EEG scoring (14) and missed the time of day in which cataplexy and sleep/wake fragmentation occurs most frequently (20).…”

Section: Introductionmentioning

confidence: 98%

“…The use of non-invasive proxy-measures of sleep/wake, such as actigraphy, plethysmography, or heartbeat rate correlates of arousal states instead of traditional polysomnography, can expedite sleep/wake determination in rodents (9)(10)(11)(12)(13)(14). In particular, the use of a highly sensitive motion detector (piezoelectric sensor) on the cage floor to monitor gross motor activity, together with breathing patterns during periods of behavioral quiescence, yields unsupervised sleep/wake detection with 90% accuracy vs. manual EEG scoring (15).…”

Section: Introductionmentioning

confidence: 99%

Rapid, noninvasive, and unsupervised detection of sleep/wake using piezoelectric monitoring for pharmacological studies in narcoleptic mice

Black

Sun

Laihsu

et al. 2017

Preprint

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BackgroundAssessment of sleep/wake by electroencephalography (EEG) and electromyography (EMG) is invasive, resource intensive, and not amenable to rapid screening at scale for drug discovery. In the preclinical development of therapeutics for narcolepsy, efficacy tests are hindered by the lack of a non-EEG/EMG based translational test of symptom severity. The current methods study offers proof-of-principle that PiezoSleep (noninvasive, unsupervised piezoelectric monitoring of gross body movement, together with respiration patterns during behavioral quiescence), can be used to determine sleep/wake as applicable to the development of wake-promoting therapeutics. First, the translational wake-maintenance score (WMS, the ratio of time during the first half of the dark period spent in long wake bouts to short sleep bouts) of the PiezoSleep narcolepsy screen was introduced as a means by which to rank narcoleptic orexin/ataxin-3 mice and wild type mice by sleep/wake fragmentation severity. Accuracy of the WMS to detect narcoleptic phenotypes were determined in genotype-confirmed orexin/ataxin-3 mice and wild type colony mates. The WMS was used to identify the most highly symptomatic mice for resource-intensive EEG/EMG studies for further analysis of specific arousal states. Second, PiezoSleep was demonstrated for use in high-throughput screening of wake-promoting compounds using modafinil in orexin/ataxin-3 and wild type mice.ResultsThe WMS detected a narcoleptic phenotype with 89% sensitivity, 92% specificity and 98% positive predictive value. A 15-fold difference in WMS differentiated wild type littermates from the most severely affected orexin/ataxin-3 mice. Follow-up EEG/EMG study indicated 82% of the orexin/ataxin-3 mice with the lowest wake-maintenance scores met or exceeded the cataplexy-occurrence threshold (≥ 3 bouts) for inclusion in therapeutic efficacy studies. In the PiezoSleep dose-response study, the ED50 for wake-promotion by modafinil was approximately 50 mg/kg in both genotypes. Using unsupervised piezoelectric monitoring, the efficacy of wake-promoting compounds can be determined in a 5-arm study with 60 mice in less than one week—a fraction of the time compared to EEG/EMG studies.ConclusionsThe WMS on the PiezoSleep narcolepsy screen quantifies the inability to sustain wakefulness and provides an accurate measure of the narcoleptic phenotype in mice. PiezoSleep offers rapid, scalable assessment of sleep/wake for high-throughput screening in drug discovery.

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“…Sato et al (2010) used a piezoelectric transducer to monitor mice and documented rapid increases in breathing rate during sleep with atonic posture, presumably in REM . They subsequently used this piezoelectric system to differentiate REM from NREM and Wake , but on the basis of immobility and perceived heart rate signals, in a small sample of wild type mice (Sato et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Noninvasive dissection of mouse sleep using a piezoelectric motion sensor

Yaghouby

Donohue

O’Hara

et al. 2016

Journal of Neuroscience Methods

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Background Changes in autonomic control cause regular breathing during NREM sleep to fluctuate during REM. Piezoelectric cage-floor sensors have been used to successfully discriminate sleep and wake states in mice based on signal features related to respiration and other movements. This study presents a classifier for noninvasively classifying REM and NREM using a piezoelectric sensor. New Method Vigilance state was scored manually in 4-second epochs for 24-hour EEG/EMG recordings in twenty mice. An unsupervised classifier clustered piezoelectric signal features quantifying movement and respiration into three states: one active; and two inactive with regular and irregular breathing respectively. These states were hypothesized to correspond to Wake, NREM, and REM respectively. States predicted by the classifier were compared against manual EEG/EMG scores to test this hypothesis. Results Using only piezoelectric signal features, an unsupervised classifier distinguished Wake with high (89% sensitivity, 96% specificity) and REM with moderate (73% sensitivity, 75% specificity) accuracy, but NREM with poor sensitivity (51%) and high specificity (96%). The classifier sometimes confused light NREM sleep—characterized by irregular breathing and moderate delta EEG power—with REM. A supervised classifier improved sensitivities to 90, 81, and 67% and all specificities to over 90% for Wake, NREM, and REM respectively. Comparison with Existing Methods Unlike most actigraphic techniques, which only differentiate sleep from wake, the proposed piezoelectric method further dissects sleep based on breathing regularity into states strongly correlated with REM and NREM. Conclusions This approach could facilitate large-sample screening for genes influencing different sleep traits, besides drug studies or other manipulations.

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Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset

Cited by 6 publications

References 13 publications

Noninvasive three-state sleep-wake staging in mice using electric field sensors

Noninvasive three-state sleep-wake staging in mice using electric field sensors

Rapid, noninvasive, and unsupervised detection of sleep/wake using piezoelectric monitoring for pharmacological studies in narcoleptic mice

Noninvasive dissection of mouse sleep using a piezoelectric motion sensor

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