Recent developments in automatic scoring of rodent sleep

Stefano Bastianini, Chiara Berteotti, Alessandro Gabrielli, Viviana Lo Martire, Alessandro Silvani, Giovanna Zoccoli


Sleep research carried out on rat and mouse model led to the publication of more than 5000 papers in the last 15 years, of which more than 500 in 2014. Wake-sleep scoring represents a crucial step of the work performed in pre-clinical sleep laboratories; it is a time consuming task and a potential source of errors affecting research outcomes. Several algorithms have been developed to perform automatic sleep scoring. Automatic scoring can accelerate the work of researchers substantially. Moreover, the use of sleep scoring algorithms facilitates the direct comparison of the results produced in different laboratories, with clear advantages from the viewpoint of the advancement of science and reduction of the number of animals used for research.

The intent of this review is to provide the readers with the last developments in scoring in rodent sleep and to stress about the need of a cross-lab and cross-species validated algorithm.



Automatic Scoring; Sleep; Rodents; Mice; Rats

Full Text:



Amici, R., Bastianini, S., Berteotti, C., Cerri, M., Del Vecchio, F., Lo Martire, V., Luppi, M., Perez, E., Silvani, A., Zamboni, G., Zoccoli, G. Sleep and bodily functions: the physiological interplay between body homeostasis and sleep homeostasis. Arch Ital Biol, 152: 66-78, 2014.

Bastianini, S., Berteotti, C., Gabrielli, A., Del Vecchio, F., Amici, R., Alexandre, C., Scammell, T.E., Gazea, M., Kimura, M., Lo Martire, V., Silvani, A., Zoccoli, G. SCOPRISM: a new algorithm for automatic sleep scoring in mice. J Neurosci Methods, 235: 277-284, 2014.

Bastianini, S., Silvani, A., Berteotti, C., Elghozi, J.L., Franzini, C., Lenzi, P., Lo Martire, V., Zoccoli, G. Sleep related changes in blood pressure in hypocretin-deficient narcoleptic mice. Sleep, 34: 213-218, 2011.

Bastianini, S., Silvani, A., Berteotti, C., Lo Martire, V., Zoccoli, G. High-amplitude theta wave bursts during REM sleep and cataplexy in hypocretin-deficient narcoleptic mice. J Sleep Res, 21: 185-188, 2012.

Bergmann, B.M., Mistlberger, R.E., Rechtschaffen, A. Period-amplitude analysis of rat electroencephalogram: stage and diurnal variations and effects of suprachiasmatic nuclei lesions. Sleep, 10: 523-536, 1987.

Brankack, J., Kukushka, V.I., Vyssotski, A.L., Draguhn, A. EEG gamma frequency and sleep-wake scoring in mice: comparing two types of supervised classifiers. Brain Res, 1322: 59-71, 2010.

Cerri, M., Mastrotto, M., Tupone, D., Martelli, D., Luppi, M., Perez, E., Zamboni, G., Amici, R. The inhibition of neurons in the central nervous pathways for thermoregulatory cold defense induces a suspended animation state in the rat. J Neurosci, 33: 2984-2993, 2013.

Chemelli, R.M., Willie, J.T., Sinton, C.M., Elmquist, J.K., Scammell, T., Lee, C., Richardson, J.A., Williams, S.C., Xiong, Y., Kisanuki, Y., Fitch, T.E., Nakazato, M., Hammer, R.E., Saper, C.B., Yanagisawa, M. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell, 98: 437-451, 1999.

Crisler, S., Morrissey, M.J., Anch, A.M., Barnett, D.W. Sleep-stage scoring in the rat using a support vector machine. J Neurosci Methods, 168: 524-534, 2008.

Dauvilliers, Y., Tafti, M. The genetic basis of sleep disorders. Curr Pharm Des, 14: 3386-3395, 2008.

Dengler, V., Westphalen, K., Koeppen, M. Disruption of circadian rhythms and sleep in critical illness and its impact on innate immunity. Curr Pharm Des2015.

Diniz Behn, C.G., Klerman, E.B., Mochizuki, T., Lin, S.C., Scammell, T.E. Abnormal sleep/wake dynamics in orexin knockout mice. Sleep, 33: 297-306, 2010.

El Helou, J., Belanger-Nelson, E., Freyburger, M., Dorsaz, S., Curie, T., La Spada, F., Gaudreault, P.O., Beaumont, E., Pouliot, P., Lesage, F., Frank, M.G., Franken, P., Mongrain, V. Neuroligin-1 links neuronal activity to sleep-wake regulation. Proc Natl Acad Sci U S A, 110: 9974-9979, 2013.

Floras, J.S. Hypertension and Sleep Apnea. Can J Cardiol, 31: 889-897, 2015.

Glin, L., Arnaud, C., Berracochea, D., Galey, D., Jaffard, R., Gottesmann, C. The intermediate stage of sleep in mice. Physiol Behav, 50: 951-953, 1991.

Gondard, E., Anaclet, C., Akaoka, H., Guo, R.X., Zhang, M., Buda, C., Franco, P., Kotani, H., Lin, J.S. Enhanced histaminergic neurotransmission and sleep-wake alterations, a study in histamine H3-receptor knock-out mice. Neuropsychopharmacology, 38: 1015-1031, 2013.

Gottesmann, C. The transition from slow-wave sleep to paradoxical sleep: evolving facts and concepts of the neurophysiological processes underlying the intermediate stage of sleep. Neurosci Biobehav Rev, 20: 367-387, 1996.

Grimaldi, D., Calandra-Buonaura, G., Provini, F., Agati, P., Pierangeli, G., Franceschini, C., Barletta, G., Plazzi, G., Montagna, P., Cortelli, P. Abnormal sleep-cardiovascular system interaction in narcolepsy with cataplexy: effects of hypocretin deficiency in humans. Sleep, 35: 519-528, 2012.

Gross, B.A., Walsh, C.M., Turakhia, A.A., Booth, V., Mashour, G.A., Poe, G.R. Open-source logic-based automated sleep scoring software using electrophysiological recordings in rats. J Neurosci Methods, 184: 10-18, 2009.

Hara, J., Beuckmann, C.T., Nambu, T., Willie, J.T., Chemelli, R.M., Sinton, C.M., Sugiyama, F., Yagami, K., Goto, K., Yanagisawa, M., Sakurai, T. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron, 30: 345-354, 2001.

Kantor, S., Mochizuki, T., Lops, S.N., Ko, B., Clain, E., Clark, E., Yamamoto, M., Scammell, T.E. Orexin gene therapy restores the timing and maintenance of wakefulness in narcoleptic mice. Sleep, 36: 1129-1138, 2013.

Kohn, M., Litchfield, D., Branchey, M., Brebbia, D.R. An automatic hybrid analyzer of sleep stages in the rat. Electroencephalogr Clin Neurophysiol, 37: 518-520, 1974.

Kreuzer, M., Polta, S., Gapp, J., Schuler, C., Kochs, E.F., and Fenzl, T. Sleep scoring made easy-Semi-automated sleep analysis software and manual rescoring tools for basic sleep research in mice. MethodsX, 2: 232-240, 2015.

Libourel, P.A., Corneyllie, A., Luppi, P.H., Chouvet, G., Gervasoni, D. Unsupervised online classifier in sleep scoring for sleep deprivation studies. Sleep, 38: 815-828, 2015.

Louis, R.P., Lee, J., Stephenson, R. Design and validation of a computer-based sleep-scoring algorithm. J Neurosci Methods, 133: 71-80, 2004.

Luppi, P.H., Peyron, C., Fort, P. Role of MCH neurons in paradoxical (REM) sleep control. Sleep, 36: 1775-1776, 2013.

Mouse Genome Sequencing, C., Waterston, R.H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J.F., Agarwal, P., Agarwala, R., Ainscough, R., Alexandersson, M., An, P., Antonarakis, S.E., Attwood, J., Baertsch, R., Bailey, J., Barlow, K., Beck, S., Berry, E., Birren, B., Bloom, T., Bork, P., Botcherby, M., Bray, N., Brent, M.R., Brown, D.G., Brown, S.D., Bult, C., Burton, J., Butler, J., Campbell, R.D., Carninci, P., Cawley, S., Chiaromonte, F., Chinwalla, A.T., Church, D.M., Clamp, M., Clee, C., Collins, F.S., Cook, L.L., Copley, R.R., Coulson, A., Couronne, O., Cuff, J., Curwen, V., Cutts, T., Daly, M., David, R., Davies, J., Delehaunty, K.D., Deri, J., Dermitzakis, E.T., Dewey, C., Dickens, N.J., Diekhans, M., Dodge, S., Dubchak, I., Dunn, D.M., Eddy, S.R., Elnitski, L., Emes, R.D., Eswara, P., Eyras, E., Felsenfeld, A., Fewell, G.A., Flicek, P., Foley, K., Frankel, W.N., Fulton, L.A., Fulton, R.S., Furey, T.S., Gage, D., Gibbs, R.A., Glusman, G., Gnerre, S., Goldman, N., Goodstadt, L., Grafham, D., Graves, T.A., Green, E.D., Gregory, S., Guigo, R., Guyer, M., Hardison, R.C., Haussler, D., Hayashizaki, Y., Hillier, L.W., Hinrichs, A., Hlavina, W., Holzer, T., Hsu, F., Hua, A., Hubbard, T., Hunt, A., Jackson, I., Jaffe, D.B., Johnson, L.S., Jones, M., Jones, T.A., Joy, A., Kamal, M., Karlsson, E.K., Karolchik, D., Kasprzyk, A., Kawai, J., Keibler, E., Kells, C., Kent, W.J., Kirby, A., Kolbe, D.L., Korf, I., Kucherlapati, R.S., Kulbokas, E.J., Kulp, D., Landers, T., Leger, J.P., Leonard, S., Letunic, I., Levine, R., Li, J., Li, M., Lloyd, C., Lucas, S., Ma, B., Maglott, D.R., Mardis, E.R., Matthews, L., Mauceli, E., Mayer, J.H., McCarthy, M., McCombie, W.R., McLaren, S., McLay, K., McPherson, J.D., Meldrim, J., Meredith, B., Mesirov, J.P., Miller, W., Miner, T.L., Mongin, E., Montgomery, K.T., Morgan, M., Mott, R., Mullikin, J.C., Muzny, D.M., Nash, W.E., Nelson, J.O., Nhan, M.N., Nicol, R., Ning, Z., Nusbaum, C., O'Connor, M.J., Okazaki, Y., Oliver, K., Overton-Larty, E., Pachter, L., Parra, G., Pepin, K.H., Peterson, J., Pevzner, P., Plumb, R., Pohl, C.S., Poliakov, A., Ponce, T.C., Ponting, C.P., Potter, S., Quail, M., Reymond, A., Roe, B.A., Roskin, K.M., Rubin, E.M., Rust, A.G., Santos, R., Sapojnikov, V., Schultz, B., Schultz, J., Schwartz, M.S., Schwartz, S., Scott, C., Seaman, S., Searle, S., Sharpe, T., Sheridan, A., Shownkeen, R., Sims, S., Singer, J.B., Slater, G., Smit, A., Smith, D.R., Spencer, B., Stabenau, A., Stange-Thomann, N., Sugnet, C., Suyama, M., Tesler, G., Thompson, J., Torrents, D., Trevaskis, E., Tromp, J., Ucla, C., Ureta-Vidal, A., Vinson, J.P., Von Niederhausern, A.C., Wade, C.M., Wall, M., Weber, R.J., Weiss, R.B., Wendl, M.C., West, A.P., Wetterstrand, K., Wheeler, R., Whelan, S., Wierzbowski, J., Willey, D., Williams, S., Wilson, R.K., Winter, E., Worley, K.C., Wyman, D., Yang, S., Yang, S.P., Zdobnov, E.M., Zody, M.C., Lander, E.S. Initial sequencing and comparative analysis of the mouse genome. Nature, 420: 520-562, 2002.

Palagini, L., Drake, C.L., Gehrman, P., Meerlo, P., Riemann, D. Early-life origin of adult insomnia: does prenatal-early-life stress play a role? Sleep Med, 16: 446-456, 2015.

Paterson, L.M., Nutt, D.J., Wilson, S.J. Sleep and its disorders in translational medicine. J Psychopharmacol, 25: 1226-1234, 2011.

Robert, C., Guilpin, C., Limoge, A. Automated sleep staging systems in rats. J Neurosci Methods, 88: 111-122, 1999.

Romeijn, N., Raymann, R.J., Most, E., Te Lindert, B., Van Der Meijden, W.P., Fronczek, R., Gomez-Herrero, G., Van Someren, E.J. Sleep, vigilance, and thermosensitivity. Pflugers Arch, 463: 169-176, 2012.

Ronzhina, M., Janousek, O., Kolarova, J., Novakova, M., Honzik, P., Provaznik, I. Sleep scoring using artificial neural networks. Sleep Med Rev, 16: 251-263, 2012.

Rytkonen, K.M., Zitting, J., Porkka-Heiskanen, T. Automated sleep scoring in rats and mice using the naive Bayes classifier. J Neurosci Methods, 202: 60-64, 2011.

Sateia, M.J. International classification of sleep disorders-third edition: highlights and modifications. Chest, 146: 1387-1394, 2014

Sharma, R., Sahota, P., Thakkar, M.M. Role of adenosine and the orexinergic perifornical hypothalamus in sleep-promoting effects of ethanol. Sleep, 37: 525-533, 2014.

Silvani, A., Bastianini, S., Berteotti, C., Cenacchi, G., Leone, O., Lo Martire, V., Papa, V., Zoccoli, G. Sleep and cardiovascular phenotype in middle-aged hypocretin-deficient narcoleptic mice. J Sleep Res, 23: 98-106, 2014.

Silvani, A., Grimaldi, D., Barletta, G., Bastianini, S., Vandi, S., Pierangeli, G., Plazzi, G., Cortelli, P. Cardiovascular variability as a function of sleep-wake behaviour in narcolepsy with cataplexy. J Sleep Res, 22: 178-184, 2013.

Spiegel, K., Tasali, E., Leproult, R., Van Cauter, E. Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol, 5: 253-261, 2009.

Sunagawa, G.A., Sei, H., Shimba, S., Urade, Y., Ueda, H.R. FASTER: an unsupervised fully automated sleep staging method for mice. Genes Cells, 18: 502-518, 2013.

Toth, L.A., Bhargava, P. Animal models of sleep disorders. Comp Med, 63: 91-104, 2013.

Vassalli, A., Dellepiane, J.M., Emmenegger, Y., Jimenez, S., Vandi, S., Plazzi, G., Franken, P., Tafti, M. Electroencephalogram paroxysmal theta characterizes cataplexy in mice and children. Brain, 136: 1592-1608, 2013.

Veasey, S.C., Valladares, O., Fenik, P., Kapfhamer, D., Sanford, L., Benington, J., Bucan, M. An automated system for recording and analysis of sleep in mice. Sleep, 23: 1025-1040, 2000.

Vivaldi, E.A., Bassi, A. Frequency domain analysis of sleep EEG for visualization and automated state detection. Conf Proc IEEE Eng Med Biol Soc, 1: 3740-3743, 2006.



  • There are currently no refbacks.