Circadiana: Constant light desynchronizes mammalian clock neurons

Constant light desynchronizes mammalian clock neurons

Hidenobu Ohta, Shin Yamazaki & Douglas G McMahon

Department of Biological Sciences, Vanderbilt University, VU Station B, Box 35-1634, Nashville, Tennessee 37235-1634, USA.
Correspondence should be addressed to Douglas G McMahon (douglas.g.mcmahon@vanderbilt.edu )

ABSTRACT: Circadian organization can be disrupted by constant light, resulting in behavioral arrhythmicity or 'splitting' of rhythms of activity and rest. By imaging molecular rhythms of individual clock neurons in explanted mouse clock nuclei, we now find that constant light desynchronizes clock neurons but does not compromise their ability to generate circadian rhythms. Cellular synchrony within clock nuclei is disrupted during arrhythmicity, whereas neurons in the left and right clock nuclei cycle in antiphase during 'splitting.'

Our findings resolve a basic question regarding the mammalian brain biological clock: at what level of organization is rhythmicity disrupted by external stimuli? Clearly, constant light disrupts circadian behavioral rhythms by disrupting the cellular organization of the SCN clock. The asynchronous but robust individual cellular rhythms in the SCN from arrhythmic LL miceindicate that disruption of behavioral and SCN tissue-level rhythmicity is not the result of stopping the core molecular clock mechanism of individual neuronal oscillators. Circadian rhythm generation by mammalian biological clock neurons apparently persists at the cellular and molecular levels even as behavioral rhythmicity is blunted or reorganized by constant light; however, normal temporal organization of cellular rhythms within the clock nuclei is lost under these conditions. Coherent organization of neuronal population rhythms within the SCN is critical for driving robust circadian locomotor rhythms, and each nucleus of the SCN pair is evidently capable of independently driving a component of locomotor behavior. Loss of cellular synchrony is also a mechanism for damping circadian molecular oscillations in peripheral tissue circadian oscillators. At least some peripheral circadian oscillators can show self-sustained individual cell rhythms but lack coupling mechanisms that maintain tissue-level temporal organization (for example, fibroblast cell rhythms). Thus, the SCN is distinguished from peripheral tissue oscillators by its ability to sustain phase coherence among its constituent neuronal oscillators through strong coupling interactions under normal circumstances. This ability is critical for the role of the SCN as a master pacemaker for orchestrating normal behavioral and physiological rhythmicity.