Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: a dual tract‐tracing study in rat

Abstract

The suprachiasmatic nucleus (SCN) contains a master clock for most circadian rhythms in mammals, including daily sleep-wake cycles. The ventrolateral preoptic nucleus (VLPO) plays a key role in sleep generation and, as such, might be an important target of the SCN circadian signal. However, direct SCN projections to the VLPO are limited, suggesting that most of the SCN output to the VLPO might be conveyed indirectly. We examined this possibility by microinjecting selected known major targets of SCN efferents with biotinylated dextran-amine and/or cholera toxin B subunit, followed by analyses of retrograde labelling in the SCN and anterograde labelling in the VLPO. Retrograde labelling results confirmed that the medial preoptic area, subparaventricular zone, dorsomedial hypothalamic nucleus and posterior hypothalamic area all received projections from the SCN; these projections arose predominantly from the shell, as opposed to the core, of the SCN. Anterograde labelling results indicated that these same nuclei also projected to the VLPO, mainly its medial and ventral aspects. Comparison of the results of injections of similar sizes across different target groups indicated that the rostral part of the medial preoptic area and the caudal part of the dorsomedial hypothalamic nucleus were particularly noteworthy for the abundance of both SCN source neurons and efferent fibres and terminals in the VLPO. These results suggest that the SCN might provide indirect input to the VLPO via the medial preoptic area and the dorsomedial hypothalamic nucleus, and that these indirect neuronal pathways might play a major role in circadian control of sleep-wake cycles.

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

“…Light is the primary stimulus for tuning (entraining) the SCN rhythm period and phase with the external environment. The SCN has direct connections to other hypothalamic nuclei (Deurveilher et al, 2002). This multistage processor provides the organism with flexibility so that environmental cues, such as food availability, ambient temperature and social interactions, can be integrated with the clock signal to sculpt an adaptive pattern of rhythmic daily activities (Saper et al, 2005).…”

“…The duration of wakefulness predicts the amount of SWS regardless of the circadian phase. The circadian component of the sleep propensity function is presumably regulated by the SCN via indirect innervation of the sleep promoting centre, which resides in the ventrolateral preoptic nucleus (Deurveilher et al, 2002). …”

Two forces for arousal: Pitting hunger versus circadian influences and identifying neurons responsible for changes in behavioral arousal

“…Brain regions that are activated by VMH, and are likely involved in arousalactivating pathways, include DMH and LH, which have both been extensively studied in the context of mediating arousal in the anticipation of food (19)(20)(21)(22)(23)(24). DMH receives direct projections from SCN (25) and is likely a relay nucleus involved in mediating the arousal responses of the light-entrainable oscillator. In addition, when energy homeostasis is low, activation of DMH is uncoupled from that of the SCN, and the overall activity is mandated by the temporal availability of a timed meal (26).…”

Endocannabinoid signaling in hypothalamic circuits regulates arousal from general anesthesia in mice

“…Although the exact mechanism underlying arousal from anesthesia is unknown, ample evidence suggests a remarkable similarity between anesthesia-induced unconsciousness and deep sleep (1,3,4,6,8). The hypothalamus is a key brain region for regulation of sleep and wakefulness (9)(10)(11)(12)(13). Specifically, the dorsomedial nucleus of the hypothalamus (DMH) conveys and reorganizes circadian rhythms of sleep and wakefulness from the suprachiasmatic nucleus to both the wake-promoting perifornical area (Pef) and the sleep-promoting ventrolateral preoptic nucleus (VLPO) (9)(10)(11)(12)(13).…”

“…The hypothalamus is a key brain region for regulation of sleep and wakefulness (9)(10)(11)(12)(13). Specifically, the dorsomedial nucleus of the hypothalamus (DMH) conveys and reorganizes circadian rhythms of sleep and wakefulness from the suprachiasmatic nucleus to both the wake-promoting perifornical area (Pef) and the sleep-promoting ventrolateral preoptic nucleus (VLPO) (9)(10)(11)(12)(13). The DMH receives both GABAergic innervation from the suprachiasmatic nucleus (SCN) (9)(10)(11)(12)(13) and glutamatergic innervation from the prelimbic and infralimbic areas of the prefrontal cortex (PFC) (14) and then sends GABAergic axons innervating VLPO GABA-containing neurons and glutamatergic axons innervating Pef orexin-containing neurons (Supplemental Figure 1; supplemental material available online with this article; https:// doi.org/10.1172/JCI91038DS1) (9)(10)(11)(12)(13).…”