Cryptochrome-Deficient Mice Lack Circadian Electrical Activity in the Suprachiasmatic Nuclei

Jul 18, 2002Current biology : CB

Mice without cryptochrome protein lack daily electrical rhythms in their brain’s internal clock

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Abstract

SCN neurons from mCry-deficient mice lack circadian oscillations in firing patterns when kept in constant darkness.

Circadian rhythms in mammals are regulated by clock genes through feedback loops.
The Cryptochrome 1 and 2 genes are essential for normal circadian function.
mCry1/mCry2 double-mutant mice show no rhythmic clock gene expression and arrhythmic behavior.
In constant darkness, SCN neurons from mCry-deficient mice do not exhibit electrical activity patterns associated with circadian rhythms.
Under normal light-dark conditions, mCry-deficient mice display a single peak in neuronal activity shortly after day onset, which may contribute to their normal behavior.

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The mammalian master clock driving circadian rhythmicity in physiology and behavior resides within the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Circadian rhythms are generated by a set of clock genes via intertwined negative and positive autoregulatory transcription-translation feedback loops. The Cryptochrome 1 and 2 genes are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel-running behavior and lack of rhythmic clock gene expression in mCry1/mCry2 double-mutant mice in constant darkness. In the present study, using real-time multiunit electrode activity recordings in hypothalamic slices, we show that SCN neurons from mCry-deficient mice kept in constant darkness lack circadian oscillations in firing patterns. This proves that cryptochromes, and thus an intact circadian clockwork, are prerequisites for circadian electrical activity in SCN neurons. Interestingly, when mCry-deficient mice were kept in normal light-dark conditions and SCN slices were prepared 2 hr after the beginning of the day, a single noncircadian peak in neuronal activity was detected. This light-induced rise in electrical activity of the SCN may explain why mCry-deficient mice lack the arrhythmic short bouts of wheel-running activity and instead show apparently normal behavior in normal day-night cycles.

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Cryptochrome-Deficient Mice Lack Circadian Electrical Activity in the Suprachiasmatic Nuclei

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