The steady growth of researchers and clinicians in the sleep field attests to the continued interest in the scientific study of sleep and the management of patients with sleep disorders, and anyone involved in this exciting field should find this work to be an invaluable reference. Basic and clinical science researchers who study sleep science as well as clinicians who are seeking evidence-based diagnostic tools and treatments for patients suffering from sleep disorders.
Also useful for polysomnographic technologists and other allied health professionals, as well as medical specialists and primary care physicians. Clete A. Kushida, M. He has conducted basic and clinical sleep research since , has served as principal investigator for numerous federally and industry supported research studies, and has authored or edited over publications, including six books.
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Sleep as a biological problem: an overview of frontiers in sleep research. Open Access. First Online: 05 November Introduction From a historical perspective of sleep research One feels tired and falls asleep every night and wakes feeling refreshed every morning.
Sleep Science: In the Era of Screens, Rest is Crucial
Two-photon microscopy, another standard technique for cellular physiology in vivo, recently began to be used in sleep research. Currently available two-photon microscopes cannot scan the whole brain in vivo, but can illuminate aspects of cortical dynamics different from electrophysiological insights.
Sleep is liked with learning and memory [ 41 , 42 ] in which morphological changes in dendritic spines have an important role [ 43 , 44 ]. The observation of dendritic spines in the cortex in vivo have shown that sleep contributes to turnover of dendritic spines in immature mice [ 45 , 46 , 47 ].
To gain precise understanding of spatio-temporal dynamics of the cortex during natural sleep, we designed and constructed the two-photon imaging system for naturally sleeping animals, which allow to visualize physiology and morphology of cortical cells during wakefulness, SWS, and REM sleep Fig. Fluorescence imaging of the sleeping brain makes it possible to directly answer open questions in neurophysiology of sleep e.
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Open image in new window. A neuron in Fig. Let us briefly consider the number of mutagenized mice we have to examine. The expected number E 1 of mutagenized mice showing sleep abnormality is proportional to the number of mice screened N. Because the majority of screened mice show sleep abnormalities by chance or due to the summation of weak effects derived from multiple gene mutations, most of their offspring do not show sleep abnormality similar to their father.
We usually examine whether sleep abnormality is heritable using 15—20 male mice of N2; then, if the pedigree passes the heritability test, we obtain a total of 60— N2 male mice for linkage analysis. Linkage analysis gives us a LOD score, which indicates the likelihood of genetic loci linked to a certain phenotype.
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Importantly, the LOD score depends on the extent of the phenotype. As shown in Fig. Higher LOD scores mean a stronger sleep phenotype if the number of N2 mice is constant. However, it is well worth examining the homozygous mutants because homozygous mutants may have stronger and more robust sleep abnormality than heterozygous mutants.
Through this effort, we have established several pedigrees showing sleep abnormalities, including Sleepy and Dreamless mutant pedigrees. Sleepy mutant mice are characterized by shorter daily wake time, while Dreamless mutant mice show reduced time spent in REM sleep and short REM sleep episode duration. We are now working on to elucidate how the Sleepy and Dreamless genes regulate sleep and are continuing the screening of mutagenized animals to establish another sleep abnormal pedigree and identify another sleep regulatory gene.
Acknowledgments We thank Dr.
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