The Suprachiasmatic Nucleus Changes the Daily Activity of the Arcuate Nucleus α-MSH Neurons in Male Rats

Abstract

Timing of metabolic processes is crucial for balanced physiology; many studies have shown the deleterious effects of untimely food intake. The basis for this might be an interaction between the arcuate nucleus (ARC) as the main integration site for metabolic information and the suprachiasmatic nucleus (SCN) as the master clock. Here we show in male rats that the SCN influences ARC daily neuronal activity by imposing a daily rhythm on the α-MSH neurons with a peak in neuronal activity at the end of the dark phase. Bilateral SCN lesions showed a complete disappearance of ARC neuronal rhythms and unilateral SCN lesions showed a decreased activation in the ARC at the lesioned side. Moreover light exposure during the dark phase inhibited ARC and α-MSH neuronal activity. The daily inhibition of ARC neuronal activity occurred in light-dark conditions as well as in dark-dark conditions, demonstrating the inhibitory effect to be mediated by increased SCN (subjective) day neuronal activity. Injections into the SCN with the neuronal tracer cholera toxin B showed that α-MSH neurons receive direct projections from the SCN. The present study demonstrates that the SCN activates and possibly also inhibits depending on the moment of the circadian cycle ARC α-MSH neurons via direct neuronal input. The persistence of these activity patterns in fasted animals demonstrates that this SCN-ARC interaction is not necessarily satiety associated but may support physiological functions associated with changes in the sleep-wake cycle.

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

“…This is consistent with observations that altered metabolic conditions of an animal change the activity of the ARC and that of the SCN simultaneously (Yi et al, 2008; Saderi et al, 2013). Moreover, recent findings show that the SCN readily modulates glucose sensing in the ARC in a time dependent manner (Chao et al, 2016) and light not only directly changes the neuronal activity of the SCN but also that of the ARC (Guzmán-Ruiz et al, 2014) further confirming the significance of the SCN-ARC axis.…”

“…Thus, to reduce this possibility we performed a unilateral SCN lesion with a contralateral knife cut. Unilateral SCN lesions alone allow an animal to maintain its circadian rhythm (Gerkema et al, 1990; Guzmán-Ruiz et al, 2014). Hence, to ensure our observations were the result of severed interaction between the SCN and ARC and not due to damage of the retrochiasmatic area or other hypothalamic projections to the SCN and ARC, we combined unilateral SCN lesions with a contralateral knife cut, leaving the unilateral SCN, unilateral retrochiasmatic area and complete ARC intact.…”

“…In view of recent observations that lesions targeted at specific neuronal populations in the ARC resulted in deteriorated temperature, feeding, and sleep rhythms (Li et al, 2012; Wiater et al, 2013), and the observations that the SCN induces a rhythm in the ARC (Guzmán-Ruiz et al, 2014; Herrera-Moro et al, 2016), and the ARC influences the activity of the SCN (Yi et al, 2006), we hypothesized that ARC-SCN reciprocity is an essential feedback pathway for the SCN, adjusting its output and facilitating changes in its neural activity in response to physiologic and behavioral activity. To test this hypothesis, we made retrochiasmatic knife cuts to isolate the ARC from the SCN, preventing their reciprocal communication; we measured specific physiologic output, along with central and peripheral clock gene expression.…”

Central Circadian Clock Regulates Energy Metabolism

“…A robust circadian rhythm was observed in the firing activity of the ARC neurons expressing α-melanocyte-stimulating hormone (α-MSH), with the peak activity in the late dark cycle in rats. Bilateral SCN lesions blocked this rhythm and a direct projection from the SCN to the ARC was identified by neuronal tracing (Guzmán-Ruiz et al, 2014). This finding suggested a potential time-dependent regulation of the appetite by the central circadian clock.…”

Sex‐ and sub region‐dependent modulation of arcuate kisspeptin neurones by vasopressin and vasoactive intestinal peptide

“…To begin to investigate this possibility, we have examined whether ARN KISS neurones in the mouse express functional receptors for arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP), the two major neuropeptidergic outputs from the suprachiasmatic nucleus (SCN). Studies in rats and mice have identified receptors for both of these neuropeptides in the arcuate nucleus and SCN neurones are known to project to and modulate the activity of ARN neurones in the rat . In addition, many neural populations expressing VIP and AVP are also found outside the SCN and may conceivably have a role in regulating LH secretion.…”