Suprachiasmatic Nucleus Interaction with the Arcuate Nucleus; Essential for Organizing Physiological Rhythms

Abstract

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 microcuts effectively removing SCN-arcuate nucleus (ARC) interconnectivity in Wistar rats result in a loss of rhythmicity in locomotor activity, corticosterone levels, and body temperature in constant dark (DD) 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 microcuts 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.

Central Circadian Clock Regulates Energy Metabolism

“…Surgical micro-cuts that eliminate these reciprocal connections lead to arrhythmicity in locomotor activities, corticosterone levels, and body temperature in the constant darkness condition in rats. Interestingly, the SCN clock gene rhythmicity was not altered by these micro-cuts while the ARC gene rhythmicity was disrupted (Buijs et al, 2017). These findings suggest that the autonomous clock in the SCN controls the molecular clock in the ARC and potentially other brain regions through a complex neuronal projection network.…”

Interacting influences of aging and Alzheimer's disease on circadian rhythms

“…This finding suggested that abnormal clock gene rhythms or reduced coordination among rhythms might contribute to impairments in sleep–wake rhythms and cognition in AD patients. Because the SCN controls the phase of clock gene rhythms throughout the brain and body (Abraham, Prior, Granados‐Fuentes, Piwnica‐Worms, & Herzog, ; Buijs et al., ; Granados‐Fuentes, Prolo, Abraham, & Herzog, ; Yoo et al., ), the desynchrony of clock gene rhythms in extra‐SCN regions in the AD brain might result from deficits in SCN function. Alternatively, other factors might induce or contribute to attenuation or desynchrony of clock gene rhythms in extra‐SCN regions.…”

Regulation and function of extra‐SCN circadian oscillators in the brain

“…Genetic disruption of the SCN clock does not completely eliminate rhythmic dopamine release in the ARC indicating a semi‐autonomous clock machinery . Nevertheless, cutting the connections between ARC and the SCN results in desynchronization of the former . Hypothalamic regions are important control centres of many rhythmic physiological functions.…”

“…Rhythmic clock gene expression in neuroendocrine dopaminergic neurons of the ARC suggested that prolactin secretion might be under the control of the ARC oscillator . Interestingly, rats with ablated SCN‐ARC connections show arrhythmic GC levels, body temperature and locomotor activity in DD suggest a close interaction in SCN and ARC clocks in the regulation of these outputs . Guzmán‐Ruiz et al reported that the balance of α‐MSH release from the ARC together with arginine vasopressin neurons from the SCN is fundamental for the daily body temperature rhythm through projections to the MPN .…”