Genetically modified mice are used as models for a variety of human behavioral conditions. However, behavioral phenotyping can be a major bottleneck in mouse genetics because many of the classic protocols are too long and/or are vulnerable to unaccountable sources of variance, leading to inconsistent results between centers. We developed a home-cage approach using a Chora feeder that is controlled by-and sends data to-software. In this approach, mice are tested in the standard cages in which they are held for husbandry, which removes confounding variables such as the stress induced by out-of-cage testing. This system increases the throughput of data gathering from individual animals and facilitates data mining by offering new opportunities for multimodal data comparisons. In this protocol, we use a simple work-for-food testing strategy as an example application, but the approach can be adapted for other experiments looking at, e.g., attention, decision-making or memory. The spontaneous behavioral activity of mice in performing the behavioral task can be monitored 24 h a day for several days, providing an integrated assessment of the circadian profiles of different behaviors. We developed a Python-based open-source analytical platform (Phenopy) that is accessible to scientists with no programming background and can be used to design and control such experiments, as well as to collect and share data. This approach is suitable for large-scale studies involving multiple laboratories.

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Prader–Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by metabolic alteration and sleep abnormalities mostly related to rapid eye movement (REM) sleep disturbances. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in humans and mice. Here, we further explore sleep regulation of PWS by reporting a study with PWScrm+/p− mouse line, which carries a paternal deletion of Snord116. We focused our study on both macrostructural electrophysiological components of sleep, distributed among REMs and nonrapid eye movements. Of note, here, we study a novel electroencephalography (EEG) graphoelements of sleep for mouse studies, the well-known spindles. EEG biomarkers are often linked to the functional properties of cortical neurons and can be instrumental in translational studies. Thus, to better understand specific properties, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array. Our results confirm that the loss of Snord116 gene in mice influences specific properties of REM sleep, such as theta rhythms and, for the first time, the organization of REM episodes throughout sleep–wake cycles. Moreover, the analysis of sleep spindles present novel specific phenotype in PWS mice, indicating that a new catalog of sleep biomarkers can be informative in preclinical studies of PWS.