Karl Ægir Karlsson

Research

RU NEUROLAB facilities

The RU NEUROLAB just moved to a brand-new 120 square meter lab in the new RU building at Nauthólsvík. We are still settling in but the location and space is simply awesome!

RESEARCH BACKGROUND

Sleep is ubiquitous mammalian phenomenon that is also the predominant behavioral state during infancy. For example, human infants spend two thirds of their day sleeping; furthermore, more than half of that time is spent in REM sleep. In contrast, human adults spend one third of their day sleeping and less than one tenth of their total sleep time is spent in REM sleep. Sleep is also one of the last remaining mysteries of biology; all this time devoted to sleeping and we still don´t know what its for.The predominance of sleep in infancy has fueled the notion that sleep subserves important functions during early development. It was at least in part for this reason that during my graduate carreer I focused on outlining the neural substrates of sleep in infancy using traditional methods of neuroscience (in vivo electrophysiology, lesioning, tract tracing etc). This work can be accessed at the Public Library of Science website.Sleep, and its development, has remained a research focus in my lab. Currently I am running experiments aimed at documenting statistical properties of sleep development in a healthy human sample; I am employing fMRI to better understand how neurons of the hypothalamus react under various emotional conditions which may prove important for understanding narcolepsy and cataplexy. This work is done in collaboration with collegues at the Medical University of Vienna; lastly, I am establishing a zebrafish (danio rerio) model of sleep. I anticipate the zebrafish work will form the backbone of my labs research efforts over the next few years.

Sleep with the fishes

Zebrafish have for a long time been the favourite of developmental biologists and are becoming ever more popular model system in genetics. Zebrafish are cheap and easy to rear, proliferate, and express numerous homologies with other vertbrates such as: high nucleotide homology, physiology and neural anatomy. The development of robust behavioral observation methods for zebrafish will, thus, allow researchers to capitalize on the various tools developed for zebrafish in novel research venues. We are using behavioral observation methods to log sleep-wake bout durations in zebrafish with the intent of developing a zebrafish model of sleep – which is meaningfully comparable to humans.Recently, surprising statistical regularities have been revealed in the structure of bouts of sleep and wakefulness (C. C. Lo, Amaral, L.A.N., Havlin, S., Ivanov, P., Penzel, T., Peter, J.H., Stanley, H.E., 2002). This characterization of sleep offers a novel method of measuring and classifying behavioral states. In contrast to the standard in the field, this method renders sleep comparable across phylogeny and ontogeny and, thus, opens new ways of dissecting sleep at the behavioral, pharmacological, and genetic levels.In adult humans the duration of sleep bouts exhibit an exponential distribution with the rule P(t) ~ exp(-t/tau) where t is an individual sleep bout, whereas, wake bouts exhibit a power-law distribution with the rule P(t) ~ t^-(alfa) where t is an individual wake bout (C. C. Lo, Amaral, L.A.N., Havlin, S., Ivanov, P., Penzel, T., Peter, J.H., Stanley, H.E., 2002). Subsequently, it was demonstrated that the wake bouts exhibit a scale-free power law behavior with an exponent, alfa, that remains constant across species (humans, cats, rats, and mice). In contrast, sleep bout durations follow an exponential distribution where tau represents a characteristic time scale whose main determinants are body size and metabolic rate (C. C. Lo et al., 2004). In neonatal rats, both sleep and wake bouts exhibit exponential distribution immediately after birth, with a clear power-law behavior of wake bouts emerging only after the second postnatal week; this occurs in spite of very little change in the overall duration of wake bouts; tau, on the other hand, increases with age (Blumberg et al., 2005). Thus, the power-law exponent alfa is constant across multiple adult species, but switches from exponential to power-law behavior during development. In contrast, the sleep-related time constant tau varies across species and age. Importantly, the only information needed to calculate alfa and tau is sleep and wake durations; one does not need detailed information about the transitions between sleep states or information about events within a given state. Given the right measuring system, this method can be employed to the simple, genetically tractable zebrafish (Yokogawa et al., 2007; Zhdanova, 2006). Using this method renders sleep in humans and zebrafish comparable and open new venues in sleep research.The values, alfa and tau, thus, represent novel way of thinking about sleep, and offer a novel, simpler method of characterizing sleep states; a method that is based on the stability of behavioral states. This novel method of characterizing sleep states could become the new standard of classifying sleep, its disorders, and its development through the life-span.

References

Blumberg, M. S., Seelke, A. M., Lowen, S. B., & Karlsson, K. A. (2005). Dynamics of sleep-wake cyclicity in developing rats. Proc Natl Acad Sci U S A, 102(41), 14860-14864.Lo, C. C., Amaral, L.A.N., Havlin, S., Ivanov, P., Penzel, T., Peter, J.H., Stanley, H.E. (2002). Dynamics of sleep-wake transitions during sleep. Europhysics Letters, 57(5), 625-631.Lo, C. C., Chou, T., Penzel, T., Scammell, T. E., Strecker, R. E., Stanley, H. E., et al. (2004). Common scale-invariant patterns of sleep-wake transitions across mammalian species. Proc Natl Acad Sci U S A, 101(50), 17545-17548.Yokogawa, T., Marin, W., Faraco, J., Pezeron, G., Appelbaum, L., Zhang, J., et al. (2007). Characterization of sleep in zebrafish and insomnia in hypocretin receptor mutants. PLoS Biol, 5(10), 2379-2397.Zhdanova, I. V. (2006). Sleep in zebrafish. Zebrafish, 3(2), 225.