scholarly journals Astrocytic Modulation of Neuronal Activity in the Suprachiasmatic Nucleus: Insights from Mathematical Modeling

2020 ◽  
Vol 35 (3) ◽  
pp. 287-301
Author(s):  
Natthapong Sueviriyapan ◽  
Chak Foon Tso ◽  
Erik D. Herzog ◽  
Michael A. Henson
Keyword(s):  
Circadian Rhythm ◽  
Suprachiasmatic Nucleus ◽  
Neuronal Activity ◽  
Clock Genes ◽  
Rhythmic Activity ◽  
Neuronal Population ◽  
Circadian Period ◽  
Circadian Oscillators ◽  
Bidirectional Interactions ◽  
The Impact

The suprachiasmatic nucleus (SCN) of the hypothalamus consists of a highly heterogeneous neuronal population networked together to allow precise and robust circadian timekeeping in mammals. While the critical importance of SCN neurons in regulating circadian rhythms has been extensively studied, the roles of SCN astrocytes in circadian system function are not well understood. Recent experiments have demonstrated that SCN astrocytes are circadian oscillators with the same functional clock genes as SCN neurons. Astrocytes generate rhythmic outputs that are thought to modulate neuronal activity through pre- and postsynaptic interactions. In this study, we developed an in silico multicellular model of the SCN clock to investigate the impact of astrocytes in modulating neuronal activity and affecting key clock properties such as circadian rhythmicity, period, and synchronization. The model predicted that astrocytes could alter the rhythmic activity of neurons via bidirectional interactions at tripartite synapses. Specifically, astrocyte-regulated extracellular glutamate was predicted to increase neuropeptide signaling from neurons. Consistent with experimental results, we found that astrocytes could increase the circadian period and enhance neural synchronization according to their endogenous circadian period. The impact of astrocytic modulation of circadian rhythm amplitude, period, and synchronization was predicted to be strongest when astrocytes had periods between 0 and 2 h longer than neurons. Increasing the number of neurons coupled to the astrocyte also increased its impact on period modulation and synchrony. These computational results suggest that signals that modulate astrocytic rhythms or signaling (e.g., as a function of season, age, or treatment) could cause disruptions in circadian rhythm or serve as putative therapeutic targets.

scholarly journals Divergent Roles of Clock Genes in Retinal and Suprachiasmatic Nucleus Circadian Oscillators

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38985 ◽  
Author(s):  
Guo-Xiang Ruan ◽  
Karen L. Gamble ◽  
Michael L. Risner ◽  
Laurel A. Young ◽  
Douglas G. McMahon
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Circadian Oscillators

Isoperiodic neuronal activity in suprachiasmatic nucleus of the rat

1992 ◽  
Vol 263 (1) ◽  
pp. R51-R58 ◽  
Author(s):  
J. D. Miller ◽  
C. A. Fuller
Keyword(s):  
Circadian Rhythms ◽  
Population Size ◽  
Suprachiasmatic Nucleus ◽  
Neuronal Activity ◽  
Vasoactive Intestinal Polypeptide ◽  
Phase Stability ◽  
Neuronal Population ◽  
Neuron Population ◽  
Strongly Coupled ◽  
Bursting Activity

A subpopulation of neurons in the suprachiasmatic nucleus (SCN) is shown here to exhibit isoperiodic bursting activity. The period of discharge in these cells may be lengthened or the periodicity may be transiently disrupted by photic stimulation. It is suggested that many, if not all, of these cells are vasoactive intestinal polypeptide (VIP) neurons. It is shown that the ultradian periodicity of these cells, estimates of the VIP neuron population size in the SCN, effects of partial lesions on tau (period), and estimates of the phase stability of SCN-driven circadian rhythms are consistent with a strongly coupled, multioscillator model of circadian rhythmicity, in which the oscillator population constitutes a restricted subset of the SCN neuronal population.

Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats

2007 ◽  
Vol 293 (5) ◽  
pp. E1325-E1334 ◽  
Author(s):  
Maristela O. Poletini ◽  
De'Nise T. McKee ◽  
Jessica E. Kennett ◽  
Jamie Doster ◽  
Marc E. Freeman
Keyword(s):  
Circadian Rhythm ◽  
Locus Coeruleus ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Random Sequence ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Gene Expressions ◽  
Circadian Time

The nature of the circadian signal from the suprachiasmatic nucleus (SCN) required for prolactin (PRL) surges is unknown. Because the SCN neuronal circadian rhythm is determined by a feedback loop of Period (Per) 1, Per2, and circadian locomotor output cycles kaput ( Clock) gene expressions, we investigated the effect of SCN rhythmicity on PRL surges by disrupting this loop. Because lesion of the locus coeruleus (LC) abolishes PRL surges and these neurons receive SCN projections, we investigated the role of SCN rhythmicity in the LC neuronal circadian rhythm as a possible component of the circadian mechanism regulating PRL surges. Cycling rats on proestrous day and estradiol-treated ovariectomized rats received injections of antisense or random-sequence deoxyoligonucleotide cocktails for clock genes ( Per1, Per2, and Clock) in the SCN, and blood samples were taken for PRL measurements. The percentage of tyrosine hydroxylase-positive neurons immunoreactive to Fos-related antigen (FRA) was determined in ovariectomized rats submitted to the cocktail injections and in a 12:12-h light:dark (LD) or constant dark (DD) environment. The antisense cocktail abolished both the proestrous and the estradiol-induced PRL surges observed in the afternoon and the increase of FRA expression in the LC neurons at Zeitgeber time 14 in LD and at circadian time 14 in DD. Because SCN afferents and efferents were probably preserved, the SCN rhythmicity is essential for the magnitude of daily PRL surges in female rats as well as for LC neuronal circadian rhythm. SCN neurons therefore determine PRL secretory surges, possibly by modulating LC circadian neuronal activity.

scholarly journals Circadian rhythm–dependent and circadian rhythm–independent impacts of the molecular clock on type 3 innate lymphoid cells

2019 ◽  
Vol 4 (40) ◽  
pp. eaay7501 ◽  
Author(s):  
Qianli Wang ◽  
Michelle L. Robinette ◽  
Cyrielle Billon ◽  
Patrick L. Collins ◽  
Jennifer K. Bando ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Clock Genes ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Rhythmic Expression ◽  
Interleukin 22 ◽  
Circadian Clock Genes ◽  
Group 3 ◽  
Type 3 ◽  
The Impact

Many gut functions are attuned to circadian rhythm. Intestinal group 3 innate lymphoid cells (ILC3s) include NKp46+ and NKp46− subsets, which are RORγt dependent and provide mucosal defense through secretion of interleukin-22 (IL-22) and IL-17. Because ILC3s highly express some key circadian clock genes, we investigated whether ILC3s are also attuned to circadian rhythm. We noted circadian oscillations in the expression of clock and cytokine genes, such as REV-ERBα, IL-22, and IL-17, whereas acute disruption of the circadian rhythm affected cytokine secretion by ILC3s. Because of prominent and rhythmic expression of REV-ERBα in ILC3s, we also investigated the impact of constitutive deletion of REV-ERBα, which has been previously shown to inhibit the expression of a RORγt repressor, NFIL3, while also directly antagonizing DNA binding of RORγt. Development of the NKp46+ ILC3 subset was markedly impaired, with reduced cell numbers, RORγt expression, and IL-22 production in REV-ERBα–deficient mice. The NKp46− ILC3 subsets developed normally, potentially due to compensatory expression of other clock genes, but IL-17 secretion paradoxically increased, probably because RORγt was not antagonized by REV-ERBα. We conclude that ILC3s are attuned to circadian rhythm, but clock regulator REV-ERBα also has circadian-independent impacts on ILC3 development and functions due to its roles in the regulation of RORγt.

Identification of the suprachiasmatic nucleus in birds

2001 ◽  
Vol 280 (4) ◽  
pp. R1185-R1189 ◽  
Author(s):  
Takashi Yoshimura ◽  
Shinobu Yasuo ◽  
Yoshikazu Suzuki ◽  
Eri Makino ◽  
Yuki Yokota ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Japanese Quail ◽  
Clock Genes ◽  
Biological Clock ◽  
Circadian Oscillators ◽  
Circadian Clock Genes ◽  
Dim Light

Circadian rhythms are generated by an internal biological clock. The suprachiasmatic nucleus (SCN) in the hypothalamus is known to be the dominant biological clock regulating circadian rhythms in mammals. In birds, two nuclei, the so-called medial SCN (mSCN) and the visual SCN (vSCN), have both been proposed to be the avian SCN. However, it remains an unsettled question which nuclei are homologous to the mammalian SCN. We have identified circadian clock genes in Japanese quail and demonstrated that these genes are expressed in known circadian oscillators, the pineal and the retina. Here, we report that these clock genes are expressed in the mSCN but not in the vSCN in Japanese quail, Java sparrow, chicken, and pigeon. In addition, mSCN lesions eliminated or disorganized circadian rhythms of locomotor activity under constant dim light, but did not eliminate entrainment under light-dark (LD) cycles in pigeon. However, the lesioned birds became completely arrhythmic even under LD after the pineal and the eye were removed. These results indicate that the mSCN is a circadian oscillator in birds.

scholarly journals Activation of glycine receptor phase-shifts the circadian rhythm in neuronal activity in the mouse suprachiasmatic nucleus

2011 ◽  
Vol 589 (9) ◽  
pp. 2287-2300 ◽  
Author(s):  
Jérôme Mordel ◽  
Diana Karnas ◽  
Alexey Inyushkin ◽  
Etienne Challet ◽  
Paul Pévet ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Suprachiasmatic Nucleus ◽  
Neuronal Activity ◽  
Glycine Receptor ◽  
Phase Shifts ◽  
Receptor Phase

scholarly journals Housing temperature affects the circadian rhythm of hepatic metabolism and clock genes

2020 ◽  
Vol 247 (2) ◽  
pp. 183-195
Author(s):  
Anjara Rabearivony ◽  
Huan Li ◽  
Shiyao Zhang ◽  
Siyu Chen ◽  
Xiaofei An ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Clock Genes ◽  
Hepatic Metabolism ◽  
Serum Levels ◽  
Phase Changes ◽  
External Temperature ◽  
Glucose Levels ◽  
Circadian Oscillators ◽  
Housing Temperature ◽  
Advanced Phase

Environmental temperature remarkably impacts on metabolic homeostasis, raising a serious concern about the optimum housing temperature for translational studies. Recent studies suggested that mice should be housed slightly below their thermoneutral temperature (26°C). On the other hand, the external temperature, also known as a zeitgeber, can reset the circadian rhythm. However, whether housing temperature affects the circadian oscillators of the liver remains unknown. Therefore, we have compared the effect of two housing temperatures, namely 21°C (conventional; TC) and 26°C (thermoneutral; TN), on the circadian rhythms in mice. We found that the rhythmicity of food intake showed an advanced phase at TC, while the activity was more robust at TN, with a prolonged period onset. The serum levels of norepinephrine were remarkably induced at TC, but failed to oscillate rhythmically at both temperatures. Likewise, circulating glucose levels were increased but were non-rhythmic under TC. Both total cholesterol and triglycerides levels were induced at TN, but showed an advanced phase under TC. Additionally, the expression of hepatic metabolic genes and clock genes remained rhythmic at both temperatures, with the exception of G6Pase, Fasn, Cpt1a and Cry2, at TN. Nevertheless, the liver histology examination did not show any significant changes in response to housing temperature. Although the non-consistent trends of phase changes in each temperature, our results suggest a non-reductant role of temperature in mouse internal rhythmicity resetting. Thus, the temperature-controlled internal circadian synchronization within organs should be taken into consideration when optimizing housing temperature for mice.

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