A long-held theory on circadian rhythms has been turned on its head by a study published in Science today. The findings mean that we may now be able to develop new drugs and approaches to tune the daily clock to treat sleep disorders and to aid recovery from long-distance flights.
Dr Hugh Piggins and Dr Mino Belle from the University of Manchester tested mathematical predictions made by Dr Daniel Forger and his PhD student Casey Diekman at the University of Michigan. Using electrophysiology to look at neurons in the brain's daily clock in the suprachiasmatic nuclei or SCN, Drs Belle and Piggins found that there were two basic types of neurons with very different electrical properties. One type that contained a key clock gene, per1, was able to survive at unusually high levels of excitability that would kill most neurons in the brain. Indeed, the per1 cells also showed a huge difference in their electricity level, or excitability, between day and night. The other type of cells that did not appear to make per1 had very different electrical properties and could not survive the levels of excitability displayed by per1 neurons.
On further examination the team found that the per1 cells appeared to be silent during the day because they had become so excited that they could not communicate in the typical way that most brain cells do. They had a lower, more easily traced excitability level in the morning and at dusk and were only truly silent at night. This flies in the face of accepted theory.
Dr Piggins, at Manchester's Faculty of Life Sciences, explained: "We discovered that per1 cells are coding the time of day by being silent, which is the opposite of previous expectations.
"Before researchers would have believed that these neurons were silent because they were dead or damaged, but they are alive and well and working in an unusual manner. SCN clock cells in the brain have special properties to allow them to survive in unusual states. It is the cells that do not make per1 that behave in the conventional way."
"These were surprising results because the dogma of the past 25 years has been that the daily clock signals or encodes time by increasing firing rate during the day and then dropping to a very slow rate, signalling intermittently, during the night. It doesn't do that at all, which is even more satisfying - I was part of the same group that believed this."
Dr Piggins, whose research was funded by the BBSRC, added: "Fundamental assumptions about mammalian neurons and what they do could be wrong. Our study shows the power of bringing together mathematics and physiology to understand a key problem in biology.
"We now plan to see if there are clock-like cells in other parts of the brain. It's possible we will see this pattern of activity elsewhere."