How body clock and sleep affect brain connections between night and day

WASHINGTON - Using zebrafish, Stanford University School of Medicine researchers have shown how the circadian clock and sleep affect the scope of neuron-to-neuron connections in a particular region of the brain.

In the new study, the researchers 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 Dr. Lior Appelbaum, co-first author of the study.

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.

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 night time 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.

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.

Appelbaum noted this is the first time rhythmic changes in synapse numbers have been observed in the brain of a living vertebrate.

The work also, further demonstrates the brain’s ability to reorganize and adapt to changes, said Mignot.

“It 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,” he said.

The researchers determined that the differing number of synapses between day and night was primarily regulated by the body’s internal clock but was also affected by behaviour - for instance, how much sleep the fish got.

They also identified a gene, NPTX2b, that appears to be involved in regulating the rhythmic changes in synapses.

The study appears in the latest issue of Neuron. (ANI)