The master clock becomes a servant

In mammals, a specialized 'clock' or pacemaker in the hypothalamus called the suprachiasmatic nucleus (SCN) regulates daily rhythms in behavior and body function, such as sleeping and body temperature. Rhythms in the SCN are driven intrinsically, without external inputs, leading the SCN to be considered a master clock controlling other clocks within the body. However, this idea may be incomplete, report Michael Lehman and colleagues on page 111 of this issue. The researchers found that a rhythm in the phosphorylation state of the mitogen-activated protein kinase (MAPK) within a specific region of the SCN depended on external input from the eye. Therefore, at least in one case, the SCN may not be as in control as once believed.

The authors examined the SCN of hamsters with an antibody to the phosphorylated form of MAPK and found two rhythms: one located within the outer or shell region of the SCN, which peaked during the day, and another located within its core, which peaked during the night. The image shows phosphorylated MAPK expression (red) in the core partially overlapping with another SCN core marker, calbindin (green). In animals with both eyes removed, which leaves behavioral and physiological rhythms like locomotor activity and body temperature intact, the core pattern of phosphorylated MAPK was missing, whereas the shell pattern remained. Similar results were seen when both SCNs were removed and replaced by fetal SCN transplants, presumably because the transplants had not fully re-established afferent connections. Labeling the eye with an anterograde tracer revealed eye-specific terminals in close proximity to the core SCN cells that express phosphorylated MAPK, further supporting the hypothesis that these cells receive direct input from the eye. The loss in phosphorylated MAPK expression was also not a result of deafferentation-induced cell loss, because eye removal had no effect on cell density in the SCN core region.Now that it is apparent that at least one rhythm in the SCN depends on external input, the next step is to determine the functional significance of this eye-driven rhythm.