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Journal of Neuroscience, Vol 9, 1073-1081, Copyright © 1989 by Society for Neuroscience
The mammalian circadian clock in the suprachiasmatic nuclei is reset in vitro by cAMP
RA Prosser and MU Gillette
The Neural and Behavioral Biology Program, University of Illinois at Urbana-Champaign, Urbana 61801.
A circadian clock located in the suprachiasmatic nuclei (SCN) of the
hypothalamus controls the daily behavioral and physiological rhythms of
mammals. While the mammalian circadian system has been the focus of
research for many years, very little work has been directed at
understanding its underlying biochemical mechanisms. In these experiments
we used the hypothalamic brain slice technique to investigate these
mechanisms, focusing specifically on the intrinsic resetting properties of
the circadian clock of the rat. We monitored a primary expression of the
clock or pacemaker, the circadian rhythm of electrical activity of SCN
neurons. This rhythm continues the oscillatory pattern seen in vivo for up
to 60 hr in vitro, with an activity peak near midday that shows very little
variation among SCN from different rats. The stability of the rhythm in
vitro enabled us to use the time of peak activity to monitor the phase of
the underlying pacemaker. Bath application of membrane-soluble cAMP analogs
in 1 hr pulses induced robust advances in the phase of the rhythm that
remained stable for 2 cycles. This effect depended on the phase of the
pacemaker at the time of treatment: the peak was maximally advanced (4-6
hr) by treatments during the middle of the subjective day (projected from
the donor's cycle); treatments during most of the subjective night and
early subjective day induced no phase changes. Half-maximal phase resetting
was induced at 1 x 10(-10) M concentrations of active cAMP analog.(ABSTRACT
TRUNCATED AT 250 WORDS)
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