Michelle Brandt - Stanford University Medical Center
With the help of tiny, see-through fish, Stanford University School of Medicine researchers are homing in on what happens in the brain while you sleep. In a new study, they show how the circadian clock and sleep affect the scope of neuron-to-neuron connections in a particular region of the brain, and they identified a gene that appears to regulate the number of these connections, called 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, co-first author of the study, which will appear in the Oct. 6 issue of Neuron. He said further studies using the imaging method he and his colleagues developed could shed more light on how our brain activities vary according to time of day.
Appelbaum, who is now a principal investigator in a lab at Bar-Ilan University in Israel, spent five years conducting the work while in the lab of Emmanuel Mignot, MD, PhD, professor of psychiatry and behavioral sciences. Mignot, who also directs the Stanford Center for Sleep Sciences and Medicine, is senior author of the paper; the other first author is Gordon Wang, PhD, a postdoctoral scholar in molecular and cellular physiology.
Why we need to sleep and how, exactly, sleep is restorative are two big, unanswered questions in biology. Knowing that brain performance changes throughout the day, researchers believe that daily cycles and sleep regulate "synaptic plasticity" — the ability of synapses to change strength and even form and erase. And they theorize that nighttime changes in the number and strength of synapses help recharge the brain which, in turn, benefits memory, learning and other functions.
As the researchers note in their paper, daily cycle-related changes in the number of neuron-to-neuron connections hadn't previously been shown in a living vertebrate, and the "molecular mechanisms of this type of synaptic plasticity are poorly understood." So they turned to the zebrafish, a small aquarium pet, for help.
Like humans, zebrafish are active during the day and sleep at night — something that researchers in Mignot's lab discovered in previous research. Larvae of the handy little fish also happen to be transparent, enabling researchers to look directly at the animal's neuronal network. "This can't be done in any other vertebrate animal," said Mignot, who is also the Craig Reynolds Professor of Sleep Medicine, adding that his group was aided by the imaging expertise of co-author Stephen Smith, PhD, professor of molecular and cellular physiology, and his lab.
For this study, the researchers used a fluorescence-imaging technique to monitor neural activity in the specific region of the brain that regulates sleeping and waking. With their technique, they were able to watch synapses within individual hypocretin neurons, and they showed that the number of these connections fluctuated between day and night. ...
via Number of synapses shown to vary between night and day in Stanford study of zebrafish.