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After a time-shift, mixed signals from the circadian clock

Cell Press

Circadian rhythms in mammalian behavior, physiology, and biochemistry are controlled by the central clock within a brain structure known as the suprachiasmatic nucleus (SCN). The clock is synchronized to environmental cycles of light and dark. It is well known, from everyday experience, that adjusting to new light schedules takes several days, though the details of how this adaptation takes place are not well understood. Researchers now report findings that suggest this adaptation process does not necessarily involve a gradual and synchronous adaptation by the neurons that comprise the central circadian clock--rather, that different components of the clock tend to adapt to a shifted light schedule at two different speeds.

The work is reported in the May 24 issue of Current Biology by a research team led by Johanna H. Meijer of Leiden University Medical Center in The Netherlands.

The researchers studied clock-resetting behavior in rats that were exposed to a six-hour delay of the light schedule, a shift that mimics a transition from the eastern U.S. to western Europe. By performing electrophysiological analysis of cells that constitute the central circadian clock, the researchers made a surprising discovery: one part of the clock mechanism, represented by a dorsal (upper) group of cells, exhibited oscillations in activity that corresponded to slow resetting of the clock in response to the shifted light schedule, while another part of the clock, represented by a ventral (lower) group of cells, exhibited a distinct pattern of activity that corresponded to fast resetting of the clock.

Perhaps contributing to the different behavior of the two groups of clock cells are the effects on these cells of the neurotransmitter GABA, which the researchers found to excite the cells of the dorsal SCN while inhibiting neurons in the ventral SCN. Because GABA transmits information between the ventral and dorsal SCN, such differences in effect might influence, in complex ways, how the two groups of cells adapt to a shifted light schedule.

The authors conclude that the phases of activity in the ventral and dorsal clock shift with different speeds. During a schedule shift corresponding to a transition from the U.S. to western Europe, the ventral part of the clock is immediately synchronized to the new light schedule, but the dorsal part of the clock requires several days to adjust. This results temporarily in bimodal patterns of electrical activity that are generated by the clock within the SCN. Because electrical activity is the output of the circadian clock, the findings suggest that after a significant shift in light schedule, the rest of the brain is transiently--for a duration of about six days--exposed to complex signaling patterns from the circadian clock.


The researchers include Henk Albus, Mariska J. Vansteensel, Stephan Michel, and Johanna H. Meijer of Leiden University Medical Center; and Henk Albus and Gene D. Block of the University of Virginia. Research was supported by National Institutes of Health grant and by Leids Universitair Medisch Centrum Excellent Student trajectory.

Henk Albus, Mariska J. Vansteensel, Stephan Michel, Gene D. Block, and Johanna H. Meijer: "A GABAergic Mechanism Is Necessary for Coupling Dissociable Ventral and Dorsal Regional Oscillators within the Circadian Clock." Current Biology, Vol. 15, 886-893, May 24, 2005.
