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Electrical Synapses Help the Brain’s Master Clock Tick
Many nerve cells in the suprachiasmatic nucleus, the brain’s master circadian clock, communicate by electrical synapses, according to Brown University research published in the current issue of Nature Neuroscience. The team also found that, in rats and mice, electrical synapses synchronize this critical clock, which helps regulate the daily cycles of sleeping and waking.
PROVIDENCE, R.I. — The suprachiasmatic nuclei are two small clusters of brain cells with a big job: Telling the body when it’s day and when it’s night. Brown University scientists looked inside this master clock and found some of the gears that synchronize its activity: electrical synapses.
Electrical synapses are protein channels that connect nerve cells. Unlike chemical synapses, their more common and widely understood cousins, electrical synapses pass signals using electrical current. Electrical synapses were discovered nearly 50 years ago, but were only recently found to be widespread in the brains of mammals.
To find out whether electrical synapses were at work in the suprachiasmatic nuclei, or SCN, a team led by Barry Connors, professor of neuroscience, made microelectrode recordings from pairs of nerve cells in rats and mice. When current passed through one cell, some of it appeared in other cells – a sign that electrical synapses were at work.
Researchers wanted to test the molecular basis of their finding, so they used a mouse in which the gene responsible for creating connexin36, a protein building block for electrical synapses, was removed or “knocked out.” When Connors’ team tried the microelectrode experiment with these “knockout” mice, they found that no current passed between pairs of nerve cells. The reason: The mice had no electrical synapses in their SCN.
But what role do these electrical conduits play in the brain’s master circadian clock? The team turned to Rebecca Burwell, an associate professor of psychology and neuroscience, to find out.
In Burwell’s laboratory, normal and “knockout” mice were exposed to a standard schedule – 12 hours of light, 12 of dark – for 21 days. Both kinds of mice behaved normally. Because mice are nocturnal, they slept during the day and ate and ran on an exercise wheel at night. Then the mice were placed in total darkness for long as 50 days.
“The normal mice continued to show strong circadian rhythms in the constant darkness, with a long period of activity followed by a period of quiet,” Burwell said. “Only the knockout mice showed disrupted rhythms. They fell apart, particularly for the first 10 days. They were running in short bouts during the day, as well as at night.”
This finding led the team to their final hypothesis: Electrical synapses synchronize the firing of nerve cells in the SCN, and this synchrony is essential for normal circadian rhythms. “We believe these cells communicate by electrical synapses and that this communication is important for coordinating activity in the SCN,” Connors said. “When that activity is coordinated, it sends a coherent message to the rest of the clocks in the body. It’s what allows the SCN to act as a kind of circadian conductor.”
The findings answer important questions about the SCN, which not only regulates sleep patterns but also helps control organ function, body temperature and hormone production. The work, published in the current issue of Nature Neuroscience, also sheds new light on the functions of electrical synapses, a new frontier in neuroscience.
Lead authors of the study are Michael Long, a former Brown graduate student and postdoctoral fellow who is currently a research fellow in the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology, and former Brown undergraduate Michael Jutras, now a neuroscience graduate student at Emory University. The National Institutes of Health and a Sidney A. Fox and Dorothea Doctors Fox Postdoctoral Fellowship from Brown University funded the work.