Despite efforts to understand the physiological mechanisms and functions of sleep, why we spend more than a third of our lives sleeping is still one of the great mysteries of the current neuroscience. However, the use of new simple animal models is generating novel and important results on genetic, physiological and behavioral aspects of sleep. Zebrafish (Danio rerio) constitutes an ideal model for the analysis of sleep at the systemic and molecular level, and its Physiological characteristics allow the extrapolation of these findings to phylogenetically species superiors, like the human being. Physiological mechanisms and functions of the dream constitute one of the main unknowns of current neuroscience. Be like whatever, the most revealing results in the area in recent years have been linked to the use of animal sleep models, simple and well defined and characterized. For For example, the study of sleep in the fly fruit (Drosophila melanogaster) has allowed the identification of a genetic line (minisleep) characterized by a drastic reduction in total sleep time required due to a mutation in a gene encoding a channel of voltage-dependent potassium. Although the authors did not find deficits associated with reduced sleep in this line of flies, his life was shorter. The zebrafish (Danio rerio) is a simple organism suitable for sleep analysis at the systemic and molecular level, for both practical and theoretical reasons Among the practical facilities of working with zebrafish are its price, availability and speed with which they reproduce, breed and develop. The transparency of its fabrics in the early stages of development makes direct observation and manipulation of the nervous system very easy, Similarly, the administration of drugs and other substances does not require knowledge of complex physiological techniques, as occurs with other models (rats and mice), since it is only enough to dissolve these substances in the natural environment of the animal. In this sense, the potential of zebrafish for the discovery of new drugs and their impact on the central nervous system and sleep.
The first question to answer is whether the fish sleep, and whether their sleep is comparable to that of species superiors. It is difficult to determine if fish sleep according to the strict criteria of sleep in mammals (with coordinated patterns of electroencephalographic, electrooculographic, and electromyographic). Another more consistent approach is to focus on more behavioral sleep parameters. basic, namely: a) high threshold of excitability; b) spontaneity in its occurrence and rapid reversibility towards wakefulness; c) adoption of a typical posture; and d) homeostatic regulation According to these parameters, the zebrafish presents a state comparable to sleep in mammals. In addition, the main neurotransmitters involved in the regulation of sleep in humans have been shown to play a similar role in the zebrafish dream. By mainly attending to behavioral criteria of sleep (i.e., movement), the recording of sleep in zebrafish throughout its life cycle (from day 4-5 post-fertilization) is relatively simple. In order to This requires only an infrared video camera, online tracking software and a automatic lighting system. The behavioral record of sleep together with genetic manipulation techniques allow direct study the role of specific genes in the regulation of sleep in this model (to consult the sequence zebrafish genomics, see The Danio rerio Sequencing Project, http://www.sanger.ac.uk/Projects/D_rerio/).
The use of morpholinos (synthetic molecules that block the RNA translation process) allows selectively "deactivating" genes of interest, generating fish "Knockout / knockdown" with an altered behavioral phenotype. Morpholino is injected massively when the embryos are in the unicellular phase Following this paradigm, we have started a line of research that focuses on the effect on dream of the temporary deactivation of the Kcna2 gene, which encodes one of the subunits of a voltage-dependent potassium (Kv 1.2), previously associated in mice with reductions in non-REM sleep.
(NREM, sleep without rapid eye movements; Preliminary results point out that these knockout fish have less total sleep time during the night and phenotypes associated with epilepsy (seizures), which makes sense considering that the inactivation of Kcna2 it entails the reduction of the neuronal excitability threshold. Regarding the role of sleep in various cognitive functions, research with zebrafish has generated important findings. For example, trained fish to associate a lighted part of the tank with a safe environment, and another part of the tank in the dark with an aversive environment, where electric shocks were applied to them. Fish, by nature daytime, when they were trained and tested during the day, they learned to avoid the most shocks quickly (staying in the lighted area) and showed greater retention of long-term learning (24 hours) than trained overnight. This pattern was constant across various conditions. where the fish's circadian clock was artificially manipulated. This led to the belief that melatonin (hormone secreted mainly at night) could be responsible for these fluctuations circadian. Indeed, the authors showed that the subsequent administration of melatonin during the day produced similar results to nocturnal ones, revealing the role of this hormone in hindering memory formation overnight. One of the key pieces to solving the dream enigma would be to find a beginning (perhaps at the level molecular) that unifies its function throughout development in different species. Dizzying advances in the study of sleep in zebrafish will help us understand specific aspects of the physiology of sleep in humans, if not to unravel the mystery of why we sleep.