Period Coding of Bmal1 Oscillators in the Suprachiasmatic Nucleus

Jun 30, 2012The Journal of neuroscience : the official journal of the Society for Neuroscience

Timing cycles of Bmal1 clocks in the brain’s daily rhythm center

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Abstract

The period of Bmal1 expression in the mouse suprachiasmatic nucleus (SCN) is subregion specific and preserved during culture.

Bmal1 expression oscillations are linked to the maintenance of circadian behavior.
Pharmacological and physical isolations reveal subregion-specific characteristics of Bmal1 oscillation periods.
Light conditions experienced by an animal may modulate region-specific oscillation periods in the SCN.
Intercellular coupling may not significantly affect Bmal1 oscillation, suggesting a more complex interaction.
These findings imply that the period of Bmal1 expression could play a role in coding for seasonal variations.

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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.

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Period Coding of Bmal1 Oscillators in the Suprachiasmatic Nucleus

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