scholarly journals Circadian clock neurons mediate time-of-day dependent responses to light

2018 ◽  
Author(s):  
Jeff R. Jones ◽  
Tatiana Simon ◽  
Lorenzo Lones ◽  
Erik D. Herzog

ABSTRACTCircadian (~24 h) rhythms influence nearly all aspects of physiology, including sleep/wake, metabolism, and hormone release. The suprachiasmatic nucleus (SCN) synchronizes these daily rhythms to the external light cycle, but the mechanisms by which this occurs is unclear. The neuropeptide vasoactive intestinal peptide (VIP) is the predominant contributor to synchrony within the SCN and is important for circadian light responses, but the role of VIP neurons themselves is unclear. Thus, we tested the hypothesis that rhythmic SCN VIP neurons mediate circadian light responses. Using in vivo fiber photometry recording of SCN VIP neurons we found daily rhythms in spontaneous calcium events that peaked during the subjective day and in light-evoked calcium events that exhibited the greatest response around subjective dusk. These rhythms were correlated with spontaneous and NMDA-evoked VIP release from SCN VIP neurons in vitro. Finally, in vivo hyperpolarization of VIP neurons attenuated light-induced shifts of daily rhythms in locomotion. We conclude that SCN VIP neurons are circadian and depolarize to light to modulate entrainment of daily rhythms in the SCN and behavior.

1993 ◽  
Vol 90 (21) ◽  
pp. 10130-10134 ◽  
Author(s):  
V. Rettori ◽  
N. Belova ◽  
W. L. Dees ◽  
C. L. Nyberg ◽  
M. Gimeno ◽  
...  

2001 ◽  
Vol 280 (3) ◽  
pp. H1391-H1399 ◽  
Author(s):  
F. A. J. L. Scheer ◽  
G. J. Ter Horst ◽  
J. van der Vliet ◽  
R. M. Buijs

The suprachiasmatic nucleus (SCN) is the mammalian biological clock that generates the daily rhythms in physiology and behavior. Light can phase shift the rhythm of the SCN but can also acutely affect SCN activity and output, e.g., output to the pineal. Recently, multisynaptic SCN connections to other organs were also demonstrated. Moreover, they were shown to affect those organs functionally. The aim of the present study was to investigate the role of the SCN in the regulation of the heart. First, we demonstrated that heart rate (HR) in SCN-intact, but not SCN-lesioned (SCNx), male Wistar rats had a clear circadian rhythm, which was not caused by locomotor activity. Second, we demonstrated that light at night reduces HR in intact but not in SCNx rats. Finally, we demonstrated the presence of a multisynaptic autonomic connection from SCN neurons to the heart with the retrograde pseudorabies virus tracing technique. Together, these results demonstrate that the SCN affects the heart in rats and suggest that this is mediated by a neuronal mechanism.


1995 ◽  
Vol 268 (4) ◽  
pp. E537-E545 ◽  
Author(s):  
M. Ludwig

This brief review of vasopressin (VP) and oxytocin (OT) release into the extracellular space of the supraoptic (SON) and paraventricular (PVN) nuclei focuses on recent data illustrating the significance of their intranuclear release and the potential functional consequences. With the use of in vitro techniques, it has been demonstrated that administration of exogenous OT causes local peptide release and that, in vivo, this facilitates the milk ejection reflex. These findings lead to the idea that endogenous peptides are released into the hypothalamic nuclei. Microperfusion techniques have been used to monitor the dynamics of intranuclear OT and VP release in response to distinct stimuli. It is clear that intranuclear release of OT plays a role during reproductive states (parturition and lactation) and that intranuclear release of VP and OT is involved in osmoregulation. This review discusses 1) the origin of the intranuclearly released peptides, 2) stimuli which cause release into the hypothalamic nuclei, and 3) the function of intranuclear VP and OT, e.g., regulation of local morphology, feedback mechanisms and synchronization, and the possible role in regulating autonomic function and behavior.


2003 ◽  
Vol 90 (2) ◽  
pp. 763-770 ◽  
Author(s):  
Erik D. Herzog ◽  
Rachel M. Huckfeldt

The suprachiasmatic nucleus (SCN) is the master pacemaker that drives circadian rhythms in mammalian physiology and behavior. The abilities to synchronize to daily cycles in the environment and to keep accurate time over a range of physiologic temperatures are two fundamental properties of circadian pacemakers. Recordings from a bioluminescent reporter ( Per1-luc) of Period1 gene activity in rats showed that the cultured SCN entrained to daily, 1.5°C cycles of temperature, but did not synchronize to daily light cycles. Temperature entrainment developed by 1 day after birth. Light cycles failed to affect the isolated SCN of rats aged 2 to 339 days. Entrainment to a 3-h shift in the warm-cool cycle was possible in <3 days with 3°C cycles. Importantly, Per1-luc expression in vitro was similar to that seen in vivo where peak expression occurs approximately 1 h prior to the daily increase in temperature. In addition, the firing rate of individual mouse SCN neurons continued to express near 24-h rhythms from 24–37°C. At lower temperatures, the percentage of rhythmic cells was reduced, but periodicity was temperature compensated. The results indicate that normal rhythms in brain temperature may serve to stabilize rhythmicity of the circadian system in vivo and that temperature compensation of this period is determined at the level of individual SCN cells.


1995 ◽  
Vol 15 (2) ◽  
pp. 693-703 ◽  
Author(s):  
D I Jin ◽  
S B Jameson ◽  
M A Reddy ◽  
D Schenkman ◽  
M C Ostrowski

To address the role of ras signaling in monocytic phagocytes in vivo, the expression of two dominant suppressors of in vitro ras signaling pathways, the carboxyl-terminal region of the GTPase-activating protein (GAP-C) and the DNA binding domain of the transcription factor ets-2, were targeted to this cell compartment. A 5-kb portion of the human c-fms proximal promoter was shown to direct expression of the transgenes to the monocytic lineage. As a result of the GAP-C transgene expression, ras-GTP levels were reduced in mature peritoneal macrophages by 70%. The terminal differentiation of monocytes was altered, as evidence by the accumulation of atypical monocytic cells in the blood. Mature peritoneal macrophages exhibited changes in colony-stimulating factor 1-dependent survival and structure. Further, expression of the colony-stimulating factor 1-stimulated gene urokinase plasminogen activator was inhibited in peritoneal macrophages. The results indicate that ras action is critical in monocytic cells after these cells have lost the capacity to traverse the cell cycle.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.


1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.


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