Circadian phase resetting in response to light-dark and dark-light transitions

M. Comas*, D. G. M. Beersma, R. A. Hut, S. Daan

*Corresponding author for this work

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Abstract

Phase shifting of circadian systems by light has been attributed both to parametric effects on angular velocity elicited by a tonic response to the luminance level and to nonparametric instantaneous shifts induced by a phasic response to the dark-light (D>L) and light-dark (L>D) transitions. Claims of nonparametric responses are partly based on "step-PRCs," that is, phase response curves derived from such transitions. Step-PRCs in nocturnal mammals show mostly delays after lights-on and advances after lights-off, and therefore appear incompatible with phase delays generated by light around dusk and advances by light around dawn. We have pursued this paradox with 2 experimental protocols in mice. We first use the classic step-PRC protocol on wheel running activity, using the center of gravity as a phase marker to minimize the masking effects of light. The experiment was done for 3 different light intensities (1,10, and 100 lux). D > L transitions evoke mostly delays and L > D transitions show no clear tendency to either delay or advance. Overall there is little or no circadian modulation. A 2nd protocol aimed to avoid the problem of masking by assessing phase before and after the light stimuli, both in DD. Light stimuli consisted of either a slow light intensity increase over 48 h followed by abruptly switching off the light, or an abrupt switch on followed by a slow decrease toward total darkness during 48 h. If the abrupt transitions were responsible for phase shifting, we expected large differences between the 2 stimuli. Both light stimuli yielded similar PRCs characterized by delays only with circadian modulation. The results can be adequately explained by a model in which all PRCs evoked by steps result in fact from tonic responses to the light following a step-up or preceding a step-down. In this model only the response reduction of tonic velocity change after the 1st hour is taken into account. The data obtained in both experiments are thus compatible with tonic velocity responses. Contrary to standard interpretation of step-PRCs, non-parametric responses to the transitions are unlikely since they would predict delays in response to lights-off, advances in response to lights-on, while the opposite was found. Although such responses cannot be fully excluded, parsimony does not require invocation of a role for transitions, since all the data can readily be explained by tonic velocity (parametric) effects, which must exist because of the dependence of tau on light intensity.

Original languageEnglish
Pages (from-to)425-434
Number of pages10
JournalJournal of Biological Rhythms
Volume23
Issue number5
DOIs
Publication statusPublished - Oct-2008

Keywords

  • circadian clock
  • phase resetting
  • phase response curve
  • Mus musculus
  • MICE MUS-MUSCULUS
  • PHOTIC ENTRAINMENT
  • PERIOD RESPONSES
  • HAMSTERS
  • RODENT
  • SYSTEM
  • INTEGRATION
  • RHYTHMS
  • PATHWAY
  • GENES

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