Resetting of the circadian clock by a conditioned stimulus.

Environmental light is the dominant temporal cue for the entrainment of circadian rhythms. In mammals, light entrains circadian rhythms by daily resetting a pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Although it is widely held that phase resetting by light involves cellular elements within the SCN that are uniquely responsive to photic cues, we now report that non-photic cues that reliably precede the onset of light can, through associative learning, come to activate these elements. In rats, a neutral non-photic stimulus paired with light in pavlovian conditioning trials was capable of eliciting cellular and behavioural effects characteristic of phase-dependent resetting of the pacemaker by light, the expression of the transcription factor Fos in SCN cells, and phase shifts in free-running activity and temperature rhythms. Thus an associative learning process, pavlovian conditioning, provides a means whereby environmental cues that predict light onset can come to mimic the effect of light on the SCN pacemaker and thereby bring about entrainment of circadian rhythms.