Serotonergic afferents mediate activity-dependent entrainment of the mouse circadian clock

1997 ◽  
Vol 273 (1) ◽  
pp. R265-R269 ◽  
Author(s):  
D. M. Edgar ◽  
M. S. Reid ◽  
W. C. Dement
Keyword(s):  
Circadian Clock ◽  
Wheel Running ◽  
Activity Levels ◽  
Suprachiasmatic Nuclei ◽  
Vigorous Exercise ◽  
Serotonin Content ◽  
Running Activity ◽  
Midbrain Raphe Nuclei ◽  
Activity Dependent

The circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus receives serotonergic afferents from the midbrain raphe nuclei, but the functional role of this projection is unclear. In rodents, locomotor activity increases serotonin content in the SCN, and serotonergic agonists phase shift the circadian clock in a manner closely similar to voluntary bouts of vigorous exercise, suggesting that serotonergic afferents could be part of the activity-dependent entrainment mechanism. We investigated this possibility by selectively lesioning serotonin terminals within and adjacent to the SCN by local microinjection of 5,7-dihydroxytryptamine in mice pretreated with desipramine. This treatment decreased serotonin content 96 +/- 1% and 5-hydroxyindole-3-acetic acid content below levels of detection (nearly 100%) but did not decrease norepinephrine content or neuropeptide Y immunoreactivity in the SCN. These lesions did not alter subsequent running activity levels, yet rendered mice unable to synchronize to a regularly scheduled 2-h wheel running paradigm that entrained sham-lesioned controls. Serotonin afferents are thus necessary for activity-dependent entrainment in the mouse.

Inhibition of hibernation by exercise is not affected by intergeniculate leaflets lesion in hamsters

2003 ◽  
Vol 285 (3) ◽  
pp. R690-R700 ◽  
Author(s):  
Jérôme S. Menet ◽  
Patrick Vuillez ◽  
Michel Saboureau ◽  
Paul Pévet
Keyword(s):  
Wheel Running ◽  
Length Change ◽  
Day Length ◽  
Free Access ◽  
Suprachiasmatic Nuclei ◽  
Running Activity ◽  
Dependent Behavior ◽  
Testicular Regression ◽  
Wheel Running Activity

The circadian clock of mammals, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, has been demonstrated to integrate day length change from long (LP) to short photoperiod (SP). This photoperiodic change induces in Syrian hamsters a testicular regression through melatonin action, a phenomenon that is inhibited when hamsters have free access to a wheel. The intergeniculate leaflets (IGL), which modulate the integration of photoperiod by the SCN, are a key structure in the circadian system, conveying nonphotic information such as those induced by novelty-induced wheel running activity. We tested in hamsters transferred from LP to a cold SP the effects of wheel running activity on a photoperiod-dependent behavior, hibernation. Lesions of the IGL were done to test the role of this structure in the inhibition induced by exercise of photoperiod integration by the clock. We show that wheel running activity actually inhibits hibernation not only in sham-operated animals, but also in hamsters with a bilateral IGL lesion (IGLX). In contrast, IGL-X hamsters without a wheel integrate slower to the SP but hibernate earlier compared with sham-operated animals. Moreover, some hibernation characteristics are affected by IGL lesion. Throughout the experiment at 7°C, IGL-X hamsters were in hypothermia during 18% of the experiment vs. 32% for sham-operated hamsters. Taken together, these data show that the IGL play a modulatory role in the integration of photoperiodic cues and modulate hibernation, but they are not implicated in the inhibition of hibernation induced by wheel running activity.

scholarly journals The Phosphorylation of CREB at Serine 133 Is a Key Event for Circadian Clock Timing and Entrainment in the Suprachiasmatic Nucleus

2018 ◽  
Vol 33 (5) ◽  
pp. 497-514 ◽  
Author(s):  
Kelin L. Wheaton ◽  
Katelin F. Hansen ◽  
Sydney Aten ◽  
Kyle A. Sullivan ◽  
Hyojung Yoon ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Wheel Running ◽  
Slice Culture ◽  
Creb Phosphorylation ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Free Running

Within the suprachiasmatic nucleus (SCN)—the locus of the master circadian clock— transcriptional regulation via the CREB/CRE pathway is implicated in the functioning of the molecular clock timing process, and is a key conduit through which photic input entrains the oscillator. One event driving CRE-mediated transcription is the phosphorylation of CREB at serine 133 (Ser133). Indeed, numerous reporter gene assays have shown that an alanine point mutation in Ser133 reduces CREB-mediated transcription. Here, we sought to examine the contribution of Ser133 phosphorylation to the functional role of CREB in SCN clock physiology in vivo. To this end, we used a CREB knock-in mouse strain, in which Ser133 was mutated to alanine (S/A CREB). Under a standard 12 h light-dark cycle, S/A CREB mice exhibited a marked alteration in clock-regulated wheel running activity. Relative to WT mice, S/A CREB mice had highly fragmented bouts of locomotor activity during the night phase, elevated daytime activity, and a delayed phase angle of entrainment. Further, under free-running conditions, S/A CREB mice had a significantly longer tau than WT mice and reduced activity amplitude. In S/A CREB mice, light-evoked clock entrainment, using both Aschoff type 1 and 6 h “jet lag” paradigms, was markedly reduced relative to WT mice. S/A CREB mice exhibited attenuated transcriptional drive, as assessed by examining both clock-gated and light-evoked gene expression. Finally, SCN slice culture imaging detected a marked disruption in cellular clock phase synchrony following a phase-resetting stimulus in S/A CREB mice. Together, these data indicate that signaling through CREB phosphorylation at Ser133 is critical for the functional fidelity of both SCN timing and entrainment.

scholarly journals General Anaesthesia Shifts the Murine Circadian Clock in a Time-Dependant Fashion

2021 ◽  
Vol 3 (1) ◽  
pp. 87-97
Author(s):  
Nicola M. Ludin ◽  
Alma Orts-Sebastian ◽  
James F. Cheeseman ◽  
Janelle Chong ◽  
Alan F. Merry ◽  
...  
Keyword(s):  
Circadian Clock ◽  
General Anaesthesia ◽  
Wheel Running ◽  
Phase Shifts ◽  
Time Dependent ◽  
Suprachiasmatic Nuclei ◽  
Response Curves ◽  
Inhalational Anaesthetic ◽  
Locomotor Rhythms ◽  
Time Dependent Analysis

Following general anaesthesia (GA), patients frequently experience sleep disruption and fatigue, which has been hypothesized to result at least in part by GA affecting the circadian clock. Here, we provide the first comprehensive time-dependent analysis of the effects of the commonly administered inhalational anaesthetic, isoflurane, on the murine circadian clock, by analysing its effects on (a) behavioural locomotor rhythms and (b) PER2::LUC expression in the suprachiasmatic nuclei (SCN) of the mouse brain. Behavioural phase shifts elicited by exposure of mice (n = 80) to six hours of GA (2% isoflurane) were determined by recording wheel-running rhythms in constant conditions (DD). Phase shifts in PER2::LUC expression were determined by recording bioluminescence in organotypic SCN slices (n = 38) prior to and following GA exposure (2% isoflurane). Full phase response curves for the effects of GA on behaviour and PER2::LUC rhythms were constructed, which show that the effects of GA are highly time-dependent. Shifts in SCN PER2 expression were much larger than those of behaviour (c. 0.7 h behaviour vs. 7.5 h PER2::LUC). We discuss the implications of this work for understanding how GA affects the clock, and how it may inform the development of chronotherapeutic strategies to reduce GA-induced phase-shifting in patients.

Number of Arginine-Vasopressin Neurons in the Suprachiasmatic Nuclei Is Not Related to Level or Circadian Characteristics of Wheel-Running Activity in House Mice

2004 ◽  
Vol 34 (1) ◽  
pp. 131-136 ◽  
Author(s):  
Kelly J. Hochstetler ◽  
Theodore Garland Jr. ◽  
John G. Swallow ◽  
Patrick A. Carter ◽  
Abel Bult-Ito
Keyword(s):  
Arginine Vasopressin ◽  
Wheel Running ◽  
House Mice ◽  
Suprachiasmatic Nuclei ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Vasopressin Neurons

Entrainment of the master circadian clock by scheduled feeding

2004 ◽  
Vol 287 (3) ◽  
pp. R551-R555 ◽  
Author(s):  
Marina R. Castillo ◽  
Kelly J. Hochstetler ◽  
Ronald J. Tavernier ◽  
Dana M. Greene ◽  
Abel Bult-Ito
Keyword(s):  
Circadian Clock ◽  
Wheel Running ◽  
Expression Profiles ◽  
The Novel ◽  
Suprachiasmatic Nuclei ◽  
Behavioral Rhythms ◽  
Entrainment Process ◽  
Protein Expression Profiles ◽  
Access To Food ◽  
Constant Dark

The master circadian clock, located in the mammalian suprachiasmatic nuclei (SCN), generates and coordinates circadian rhythmicity, i.e., internal organization of physiological and behavioral rhythms that cycle with a near 24-h period. Light is the most powerful synchronizer of the SCN. Although other nonphotic cues also have the potential to influence the circadian clock, their effects can be masked by photic cues. The purpose of this study was to investigate the ability of scheduled feeding to entrain the SCN in the absence of photic cues in four lines of house mouse ( Mus domesticus). Mice were initially housed in 12:12-h light/dark cycle with ad libitum access to food for 6 h during the light period followed by 4–6 mo of constant dark under the same feeding schedule. Wheel running behavior suggested and circadian PER2 protein expression profiles in the SCN confirmed entrainment of the master circadian clock to the onset of food availability in 100% (49/49) of the line 2 mice in contrast to only 4% (1/24) in line 3 mice. Mice from line 1 and line 4 showed intermediate levels of entrainment, 57% (8/14) and 39% (7/18), respectively. The predictability of entrainment vs. nonentrainment in line 2 and line 3 and the novel entrainment process provide a powerful tool with which to further elucidate mechanisms involved in entrainment of the SCN by scheduled feeding.

The ‘suprachiasmatic syndrome’: endocrine and behavioural abnormalities following lesions of the suprachiasmatic nuclei in the female rat

1977 ◽  
Vol 198 (1132) ◽  
pp. 297-314 ◽  
Keyword(s):  
Wheel Running ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Transferase Activity ◽  
Female Rat ◽  
Suprachiasmatic Nuclei ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Pineal Serotonin ◽  
Response To Stress

Lesions of the suprachiasmatic nuclei that caused failure of spontaneous ovulation in female rats consistently produced abnormalities in other functions that are normally influenced by the light-dark cycle. In such animals morning plasma corticosterone concentrations were abnormally high and evening values abnormally low though the response to stress was unaffected. Pineal serotonin N -acetyl transferase activity was abnormally high in animals killed during the day and abnormally low in those killed at night. Although the animals were in persistent be­havioural oestrus, total voluntary wheel-running activity was not con­sistently altered but was distributed evenly between the light and dark periods rather than being confined principally to the dark periods as in normal animals. Similarly the proportion of the daily water and food intake that occurred during the dark period was reduced. The incidence of these associated abnormalities was low in lesioned rats that continued to ovulate spontaneously.

scholarly journals Chronic stimulation of the hypothalamic vasoactive intestinal peptide receptor lengthens circadian period in mice and hamsters

2010 ◽  
Vol 299 (1) ◽  
pp. R379-R385 ◽  
Author(s):  
Harry Pantazopoulos ◽  
Hamid Dolatshad ◽  
Fred C. Davis
Keyword(s):  
Circadian Rhythms ◽  
Vasoactive Intestinal Peptide ◽  
Wheel Running ◽  
Third Ventricle ◽  
Luciferase Expression ◽  
Activity Levels ◽  
Circadian Period ◽  
Running Activity ◽  
Wheel Running Activity

Evidence suggests that circadian rhythms are regulated through diffusible signals generated by the suprachiasmatic nucleus (SCN). Vasoactive intestinal peptide (VIP) is located in SCN neurons positioned to receive photic input from the retinohypothalamic tract and transmit information to other SCN cells and adjacent hypothalamic areas. Studies using knockout mice indicate that VIP is essential for synchrony among SCN cells and for the expression of normal circadian rhythms. To test the hypothesis that VIP is also an SCN output signal, we recorded wheel-running activity rhythms in hamsters and continuously infused the VIP receptor agonist BAY 55-9837 in the third ventricle for 28 days. Unlike other candidate output signals, infusion of BAY 55-9837 did not affect activity levels. Instead, BAY 55-9837 lengthened the circadian period by 0.69 ± 0.04 h ( P < 0.0002 compared with controls). Period returned to baseline after infusions. We analyzed the effect of BAY 55-9837 on cultured SCN from PER2::LUC mice to determine if lengthening of the period by BAY 55-9837 is a direct effect on the SCN. Application of 10 μM BAY 55-9837 to SCN in culture lengthened the period of PER2 luciferase expression (24.73 ± 0.24 h) compared with control SCN (23.57 ± 0.26, P = 0.01). In addition, rhythm amplitude was significantly increased, consistent with increased synchronization of SCN neurons. The effect of BAY 55-9837 in vivo on period is similar to the effect of constant light. The present results suggest that VIP-VPAC2 signaling in the SCN may play two roles, synchronizing SCN neurons and setting the period of the SCN as a whole.

Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice

2013 ◽  
Vol 305 (2) ◽  
pp. E171-E182 ◽  
Author(s):  
Juha J. Hulmi ◽  
Bernardo M. Oliveira ◽  
Mika Silvennoinen ◽  
Willem M. H. Hoogaars ◽  
Arja Pasternack ◽  
...  
Keyword(s):  
Physical Activity ◽  
Body Mass ◽  
Wheel Running ◽  
Oxidative Capacity ◽  
Voluntary Exercise ◽  
Muscle Size ◽  
Mdx Mice ◽  
Activity Levels ◽  
Muscle Oxidative Capacity ◽  
Running Activity

The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3–4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice.

Sign in / Sign up

Export Citation Format

Share Document