The suprachiasmatic nucleus (SCN) is generally considered the master clock, independently driving all circadian rhythms. We recently demonstrated the SCN receives metabolic and cardiovascular feedback adeptly altering its neuronal activity. In the present study we show that micro-cuts effectively removing SCN-ARC interconnectivity in Wistar rats, result in a loss of rhythmicity in locomotor activity, corticosterone levels and body temperature in constant dark conditions. Elimination of these reciprocal connections did not affect SCN clock gene rhythmicity, but did cause the ARC to desynchronize. Moreover, unilateral SCN lesions with contralateral retrochiasmatic micro-cuts resulted in identical arrhythmicity, proving that for the expression of physiological rhythms this reciprocal SCN-ARC interaction is essential. The unaltered SCN c-Fos expression following glucose administration in disconnected animals as compared to a significant decrease in controls, demonstrates the importance of the ARC as metabolic modulator of SCN neuronal activity. Together, these results indicate that the SCN is more than an autonomous clock, and forms an essential component of a larger network controlling homeostasis. The present novel findings illustrate how an imbalance between SCN and ARC communication through circadian disruption could be involved in the etiology of metabolic disorders.
Significance Statement The suprachiasmatic nucleus (SCN) is generally considered the master clock, independently driving all circadian rhythms. The present study challenges that view and shows that for a proper functioning circadian system, SCN interaction with the arcuate nucleus (ARC) is essential. We observed that interruption of SCN-ARC communication does not affect SCN rhythmicity but causes the ARC to desynchronize. This desynchrony between SCN and ARC results in animals losing activity, temperature and corticosterone rhythmicity. As the ARC is an essential metabolic integration center, this might explain how chronic circadian or metabolic disruptions through ill-timed eating habits or shift work could cause desynchrony among hypothalamic oscillators and result in disease.
The authors declare no competing financial interests.
This work was supported by CONACyT, grant 220598 and DGAPA-UNAM, grant IG-200417.