Period coding of Bmal1 oscillators in the suprachiasmatic nucleus

J Neurosci. 2012 Jun 27;32(26):8900-18. doi: 10.1523/JNEUROSCI.5586-11.2012.

Abstract

Circadian oscillators in the suprachiasmatic nucleus (SCN) collectively orchestrate 24 h rhythms in the body while also coding for seasonal rhythms. Although synchronization is required among SCN oscillators to provide robustness for regular timekeeping (Herzog et al., 2004), heterogeneity of period and phase distributions is needed to accommodate seasonal variations in light duration (Pittendrigh and Daan, 1976b). In the mouse SCN, the heterogeneous phase distribution has been recently found in the cycling of clock genes Period 1 and Period 2 (Per1, Per2) and has been shown to reorganize by relative day lengths (Inagaki et al., 2007). However, it is not yet clearly understood what underlies the spatial patterning of Per1 and Per2 expression (Yamaguchi et al., 2003; Foley et al., 2011) and its plasticity. We found that the period of the oscillation in Bmal1 expression, a positive-feedback component of the circadian clock, preserves the behavioral circadian period under culture and drives clustered oscillations in the mouse SCN. Pharmacological and physical isolations of SCN subregions indicate that the period of Bmal1 oscillation is subregion specific and is preserved during culture. Together with computer simulations, we show that either the intercellular coupling does not strongly influence the Bmal1 oscillation or the nature of the coupling is more complex than previously assumed. Furthermore, we have found that the region-specific periods are modulated by the light conditions that an animal is exposed to. Based on these, we suggest that the period forms the basis of seasonal coding in the SCN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism*
  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Animals
  • Biological Clocks / drug effects
  • Biological Clocks / genetics
  • Biological Clocks / physiology*
  • Brain Mapping
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / genetics*
  • Cluster Analysis
  • GABA Antagonists / pharmacology
  • Gene Expression Regulation / genetics
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological
  • Motor Activity / genetics
  • Neurons / drug effects
  • Neurons / metabolism
  • Nonlinear Dynamics
  • Organ Culture Techniques
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • Photoperiod*
  • Pyridazines / pharmacology
  • Sodium Channel Blockers / pharmacology
  • Software
  • Statistics as Topic
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / metabolism*
  • Tetrodotoxin / pharmacology

Substances

  • ARNTL Transcription Factors
  • Bmal1 protein, mouse
  • GABA Antagonists
  • Luminescent Proteins
  • Period Circadian Proteins
  • Pyridazines
  • Sodium Channel Blockers
  • Tetrodotoxin
  • gabazine