Transplanted Suprachiasmatic Nucleus Determines Circadian Period

Ralph, Martin R.; Foster, Russell G.; Davis, Fred C.; Menaker, Michael

doi:10.1126/science.2305266

Cited by 1,603 publications

(876 citation statements)

References 23 publications

Supporting

Mentioning

819

Contrasting

Unclassified

Order By: Relevance

“…Compelling evidence for a diffusible output signal derives from neural tissue transplantations in which the SCN from a fetal donor is implanted into the third ventricle of an adult, SCN-lesioned host. As mentioned previously, these grafts restore activity-related behaviors such as locomotor, drinking, and gnawing rhythms (Lehman et al, 1987;Ralph et al, 1990;Silver et al, 1990). That a diffusible signal is sufficient to restore locomotor rhythmicity in SCN-lesioned hosts was demonstrated by encapsulating donor SCN tissue in a membrane that prevented neural outgrowth while allowing the diffusion of signals between graft and host (Silver et al, 1996).…”

Section: Circadian Output and Orchestration Of Endocrine Function Difmentioning

confidence: 80%

“…The initial conclusion that the SCN serves as a brain master clock has been confirmed in the subsequent 30 years by converging lines of research involving in vivo, ex vivo, and in vitro studies carried out in many different laboratories. For example, transplants of donor SCN tissue into the brains of arrhythmic, SCN-lesioned hosts restore circadian rhythmicity in behavior (Lehman et al, 1987;Ralph et al, 1990). Importantly, rhythms are restored with the period of the donor SCN, indicating that the transplanted tissue does not act by restoring host brain function but that the "clock" is contained in the transplanted tissue.…”

Section: Identification Of a Brain "Clock": From Tissue To Genementioning

confidence: 99%

See 1 more Smart Citation

The regulation of neuroendocrine function: Timing is everything

Kriegsfeld

Silver

2006

Hormones and Behavior

129

View full text Add to dashboard Cite

Hormone secretion is highly organized temporally, achieving optimal biological functioning and health. The master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates the timing of circadian rhythms, including daily control of hormone secretion. In the brain, the SCN drives hormone secretion. In some instances, SCN neurons make direct synaptic connections with neurosecretory neurons. In other instances, SCN signals set the phase of "clock genes" that regulate circadian function at the cellular level within neurosecretory cells. The protein products of these clock genes can also exert direct transcriptional control over neuroendocrine releasing factors. Clock genes and proteins are also expressed in peripheral endocrine organs providing additional modes of temporal control. Finally, the SCN signals endocrine glands via the autonomic nervous system, allowing for rapid regulation via multisynaptic pathways. Thus, the circadian system achieves temporal regulation of endocrine function by a combination of genetic, cellular, and neural regulatory mechanisms to ensure that each response occurs in its correct temporal niche. The availability of tools to assess the phase of molecular/cellular clocks and of powerful tract tracing methods to assess connections between "clock cells" and their targets provides an opportunity to examine circadian-controlled aspects of neurosecretion, in the search for general principles by which the endocrine system is organized. KeywordsCircadian; Diurnal; Endocrinel; Neurosecretion; Clock genes; Suprachiasmatic Circadian aspects of reproductionThe importance of circadian (about a day) timing in hormone production/secretion has been known since the 1950s when Everett and Sawyer determined that a stimulatory signal occurring during a narrow temporal window on the afternoon of proestrus is necessary for induction of ovulation later that night (Everett and Sawyer, 1950). Such close temporal organization is important for successful reproduction, as numerous hormone-dependent behavioral and physiological processes must be coordinated. If optimal temporal relationships are disrupted, pronounced deficits in fertility can result. For example, ovulation, behavioral estrus, fertilization, and pregnancy maintenance require a specific

show abstract

Section: Circadian Output and Orchestration Of Endocrine Function Difmentioning

confidence: 80%

Section: Identification Of a Brain "Clock": From Tissue To Genementioning

confidence: 99%

The regulation of neuroendocrine function: Timing is everything

Kriegsfeld

Silver

2006

Hormones and Behavior

129

View full text Add to dashboard Cite

show abstract

“…The SCN is the primary circadian pacemaker determining the period of circadian locomotor activity rhythms (Ralph et al, 1990). DAT-KD mice are characterized by elevated DA levels (Zhuang et al, 2001), and the SCN expresses D1 receptors.…”

Section: Elevated Dopamine Signaling Lengthened Circadian Period By Amentioning

confidence: 99%

The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms

et al. 2016

View full text Add to dashboard Cite

a b s t r a c tEndogenous circadian (~24 h) clocks regulate key physiological and cognitive processes via rhythmic expression of clock genes. The main circadian pacemaker is the hypothalamic suprachiasmatic nucleus (SCN). Mood disorders, including bipolar disorder (BD), are commonly associated with disturbed circadian rhythms. Dopamine (DA) contributes to mania in BD and has direct impact on clock gene expression. Therefore, we hypothesized that high levels of DA during episodes of mania contribute to disturbed circadian rhythms in BD. The mood stabilizer valproic acid (VPA) also affects circadian rhythms. Thus, we further hypothesized that VPA normalizes circadian disturbances caused by elevated levels of DA. To test these hypotheses, we examined locomotor rhythms and circadian gene cycling in mice with reduced expression of the dopamine transporter (DAT-KD mice), which results in elevated DA levels and manialike behavior. We found that elevated DA signaling lengthened the circadian period of behavioral rhythms in DAT-KD mice and clock gene expression rhythms in SCN explants. In contrast, we found that VPA shortened circadian period of behavioral rhythms in DAT-KD mice and clock gene expression rhythms in SCN explants, hippocampal cell lines, and human fibroblasts from BD patients. Thus, DA and VPA have opposing effects on circadian period. To test whether the impact of VPA on circadian rhythms contributes to its behavioral effects, we fed VPA to DAT-deficient Drosophila with and without functioning circadian clocks. Consistent with our hypothesis, we found that VPA had potent activity-suppressing effects in hyperactive DAT-deficient flies with intact circadian clocks. However, these effects were attenuated in DAT-deficient flies in which circadian clocks were disrupted, suggesting that VPA functions partly through the circadian clock to suppress activity. Here, we provide in vivo and in vitro evidence across species that elevated DA signaling lengthens the circadian period, an effect remediated by VPA treatment. Hence, VPA may exert beneficial effects on mood by normalizing lengthened circadian rhythm period in subjects with elevated DA resulting from reduced DAT.

show abstract

“…Furthermore, elegant transplantation experiments in hamsters showed that this structure was indeed sufficient to drive behavioural rhythms: animals in which the SCN was ablated and that then received a SCN transplant showed restored rhythms [3]. When the transplant was derived from a mutant hamster strain that had a shorter endogenous period [4], the transplanted animals showed locomotor A c c e p t e d M a n u s c r i p t activity with the mutant period [3]. The SCN sends projections to a number of brain targets where its rhythmical electrical activity interacts with neural networks governing various outputs.…”

Section: The Central Clock In the Brainmentioning

confidence: 99%

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

Dickmeis

Foulkes

2011

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

The circadian clock, an endogenous timekeeper that regulates daily rhythms of physiology, also influences the dynamic release of glucocorticoids. The release of glucocorticoids is characteristically pulsatile and is further modulated in a circadian fashion. A circadian pacemaker in the brain regulates daily rhythms of hypothalamicpituitary-adrenal axis and autonomic nervous system activity that both influence glucocorticoid release from the adrenal gland. This systemic regulation interacts with rhythms in the adrenal gland itself that are driven by its own circadian clock. One function of glucocorticoids is the regulation of cell proliferation. Depending on the tissue, this can involve both negative and positive regulation of a variety of processes, including cell differentiation and cell death. Cell proliferation is also under circadian control, and recent evidence suggests that this regulation may involve glucocorticoid signalling. Here, we review the dynamic processes participating in the interplay between the circadian clock, glucocorticoids and cell proliferation, and we discuss the potential implications for therapy.

show abstract

Transplanted Suprachiasmatic Nucleus Determines Circadian Period

Cited by 1,603 publications

References 23 publications

The regulation of neuroendocrine function: Timing is everything

The regulation of neuroendocrine function: Timing is everything

The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

Contact Info

Product

Resources

About