What can Aquarium Pets Teach us about Sleep?

Tiny, see-through fish have helped researchers determine what happens in the brain while we sleep.

Stanford University School of Medicine researchers, using tiny, see-through fish have shown how sleep and the circadian clock affect the scope of synapses in a particular brain region, and in the process, discovered a gene that may regulate the number of synapses.

"This is the first time differences in the number of synapses between day and night and between wake and sleep have been shown in a living animal," said Lior Appelbaum, PhD, study co-first author.

Publishing their results in the October 6 issue of Neuron, the researchers conducted the study with the knowledge that brain performance changes during the day, the belief that synaptic plasticity is regulated by daily cycles and sleep, a curiosity of why we need sleep and how sleep is restorative, and a theory that “nighttime changes in the number and strength of synapses help recharge the brain which, in turn, benefits memory, learning and other functions.”

With no previous research showing daily cycle-related changes in the number of synapses and a poor understanding throughout the field as to the “molecular mechanisms of this type of synaptic plasticity,” the team turned to a common aquarium pet, the zebrafish. It just so happens that zebrafish, like humans, are active during the day and sleep at night, and, oh yeah, their larvae a transparent; researchers can look right into the handy little creature’s neuronal network. This can't be done in any other vertebrate animal," said senior author, Emmanuel Mignot, MD, PhD, professor of psychiatry and behavioral sciences, and director, Stanford Center for Sleep Sciences and Medicine

Using a fluorescence-imaging technique, the investigators were able to mintor neural activity in the brain region responsible for regulated sleeping and waking, watching synapses within single hypocretin neurons. Thus, they could confirm that the number of these connections changed between day and night, the first time rhythmic changes in synapse numbers were observed in a living vertebrate’s brain, according to Applebaum.

The study findings show that the brain “gets ready for new activity by telling the neurons they have to shut down synapses during this time of day but increase them at other times of the day,” added Mignot. Study results also show that the body’s internal clock regulate the differing number of synapses between night and day, although behavior, like the amount of sleep a fish got, also affects this. Further, the investigation allowed for the identification of the NPTX2b gene, which appears to play a role in regulating rhythmic changes in synapses, although Applebaum admits that it is unlikely that only one gene is involved. But, he explained, the identification puts researchers one step closer to understanding the process.

"With these [imaging] techniques, we can look at other areas of the brain, such as the one in charge of memory, to see how sleep cycles affect synapses," said Applebaum, who added that additional studies using this method could help shed light on how brain activated differ according to time of day and further uncover what happens when we sleep.

What do these findings mean to you and your patients? Will zebrafish play a prominent role in future sleep studies and other studies of the brain and CNS?