Welcome to the Mourrain Lab
While we all experience sleep, and so believe we know what it is, sleep remains a scientific enigma. A conclusive definition of sleep has eluded researchers and probably will continue to do so until the function of sleep is fully elucidated. During the early 1980s, Dr. Irene Tobler established a working definition of sleep using behavioral criteria: (i) decreased behavioral activity (reduced mobility); (ii) site preference (e.g. bed); (iii) specific posture (e.g. lying); (iv) rapid reversibility (unlike coma); and, most importantly, (v) increased arousal threshold (offline state, no perception of the environment); and (vi) homeostatic control (sleep rebound after sleep deprivation). As of today, using the above criteria, sleep has been documented and studied in a wide range of vertebrates and invertebrates, and there is currently no clear evidence of an animal species that does not sleep.
An approach to study sleep is to use simpler organisms amenable to molecular studies such as D. melanogaster, C. elegans and Danio rerio (zebrafish). While unquestionably superb genetic model organisms, the phylogenetic distance between invertebrates and mammals has produced notable and relevant divergences in usage of neuromodulators. While most mammalian peptidergic neurotransmitter systems are not present in flies and worms, we have characterized the hypocretin (HCRT) and the “true” Melanin-Concentrating Hormone (MCH) neuropeptidergic systems in zebrafish. We have shown that, despite some differences, these circuits are mostly similar in zebrafish, with conserved functions in sleep and feeding regulation.
As vertebrates zebrafish share indeed conserved neurochemistry and broad brain organization with their mammalian counterparts. While attempting whole brain modeling with a human or a mouse is a formidable challenge, the zebrafish with fewer neurons and a smaller, more accessible brain offers a more feasible option to investigate brain and neural networks. Zebrafish studies may give the first insights of circuit dynamics from whole brain down to molecular changes during sleep. From an imaging perspective, five key advantages of studying the zebrafish brain are its (i) compact size, (ii) conservation of the neuropeptide pool, (iii) linear organization of brain regions, (iv) structural accessibility of internal nuclei (no overlaying neo- cortex), and (v) optical clarity. Using these qualities we have shown, in live animals, that both circadian rhythm and sleep regulate synaptic density over a 24h cycle.
The zebrafish represents an extremely attractive system to understand the molecular and neuronal substrates of behaviors. Zebrafish behavior assessment methods are relevant in an increasing number of experimental contexts as a result of the growing usability of video processing. Not only does video processing allow for measure automation and increased accuracy, leading to higher research throughput, it also allows the definition of entirely new measures based on features that would not be detectable or countable by manual methods. We develop novel key processing components relevant to the video-based macroscopic observation of free-swimming zebrafish during wake and sleep.
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