Development of Automated Noninvasive DiskTreadmills for Sleep Deprivation in Mice

DESCRIPTION (provided by applicant): 6. Project Summary-Abstract Modern societies face a mounting epidemic that cuts across all age groups: daily sleep loss. Cumulative sleep loss induces excessive daytime sleepiness and impairs cognitive performance. Among its many financial and physical consequences: sinking job productivity and rising auto accident rates. Clinicians increasingly note the negative effects of sleep loss on cardiovascular, metabolic, endocrine, and mental functions. The nation's increasing "sleep debt" has recently received great attention in the media. Yet, while most human sleep loss results from chronic sleep restriction (CSR), most animal studies focus on acute and total sleep deprivation. Technical difficulties in creating CSR animal models have long hindered efforts to better understand the impact of long-term partial sleep deprivation. To greatly improve this situation and directly respond to the need expressed in PA-06-028, this STTR application represents a joint effort from Pennsylvania State University (PSU) and Afasci, Inc., to develop a novel noninvasive automatic sleep restriction system for mice, an increasingly important species for studying sleep disorders. PSU has recently developed a disc-treadmill method to perform sleep deprivation in mice based on electroencephalogram (EEG) and electromyogram (EMG) sleep detection. Afasci, in collaboration with Stanford University, has developed a non-invasive sleep detection hardware/software system based on motion signals detected by a piezoelectric film that lines the mouse cage floor under a thin layer of normal bedding. We now propose to create a new apparatus, DiscTreadmillTM through the integration of EEG/EMG and noninvasive piezo sleep detection with uniquely designed disc-treadmills. This proposed Phase I project has three Specific Aims: First, we will develop a new DiscTreadmill hardware with piezo sensor and wireless data collection and control capabilities adaptable for both EEG/EMG- and/or piezo-based sleep restriction in mice. Second, we will develop software that can automatically score sleep/wake state and control sleep deprivation procedures based on EEG/EMG or piezo signals. Third, we will evaluate and validate DiscTreadmill efficacy and limitation, in particular the piezo-based sleep restriction method, by simultaneously recording EEG/EMG and piezo signals in two strains of mice that have different sleep patterns. The Phase I study will produce a uniquely engineered DiscTreadmill prototype apparatus with special software. This innovative and versatile toolkit will accelerate creating chronic sleep restriction animal models and help break the notable barrier of EEG expertise required in sleep research. The DiscTreadmill with alternative noninvasive sleep detection/restriction will assist researchers from other disciplines to link their specific topics, such as cardiovascular, metabolic, endocrinological immunological, and neurobehavioral areas with the fundamental sleep homeostatic regulation. This scalable instrumentation will ultimately facilitate sleep behavior phenotyping in transgenic animals and drug discovery related to the treatment of sleep disorders. 7. Project narrative Modern society faces an increasing "sleep debt" which has already begun to affect public health. An accumulation of sleep loss causes excessive daytime sleepiness and impairs cognition, as well as causing long-term impacts on cardiovascular, metabolic, endocrine, and mental functions. We propose to develop a novel DiscTreadmillTM apparatus that can create a mouse model of chronic sleep restriction for sleep behavior assessment and drug discovery. This powerful tool ultimately will facilitate discovering new targets and novel drugs to treat sleep and mental disorders.