scholarly journals The cholinergic forebrain arousal system acts directly on the circadian pacemaker

2016 ◽  
Vol 113 (47) ◽  
pp. 13498-13503 ◽  
Author(s):  
Glenn R. Yamakawa ◽  
Priyoneel Basu ◽  
Filomeno Cortese ◽  
Johanna MacDonnell ◽  
Danica Whalley ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Basal Forebrain ◽  
Temporal Structure ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Suprachiasmatic Nuclei ◽  
Functional Link ◽  
Substantia Innominata ◽  
Arousal System ◽  
Important System

Sleep and wake states are regulated by a variety of mechanisms. One such important system is the circadian clock, which provides temporal structure to sleep and wake. Conversely, changes in behavioral state, such as sleep deprivation (SD) or arousal, can phase shift the circadian clock. Here we demonstrate that the level of wakefulness is critical for this arousal resetting of the circadian clock. Specifically, drowsy animals with significant power in the 7- to 9-Hz band of their EEGs do not exhibit phase shifts in response to a mild SD procedure. We then show that treatments that both produce arousal and reset the phase of circadian clock activate (i.e., induce Fos expression in) the basal forebrain. Many of the activated cells are cholinergic. Using retrograde tract tracing, we demonstrate that cholinergic cells activated by these arousal procedures project to the circadian clock in the suprachiasmatic nuclei (SCN). We then demonstrate that arousal-induced phase shifts are blocked when animals are pretreated with atropine injections to the SCN, demonstrating that cholinergic activity at the SCN is necessary for arousal-induced phase shifting. Finally, we demonstrate that electrical stimulation of the substantia innominata of the basal forebrain phase shifts the circadian clock in a manner similar to that of our arousal procedures and that these shifts are also blocked by infusions of atropine to the SCN. These results establish a functional link between the major forebrain arousal center and the circadian system.

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.

Grafting fetal suprachiasmatic nuclei in the hypothalamus of old hamsters restores responsiveness of the circadian clock to a phase shifting stimulus

1994 ◽  
Vol 643 (1-2) ◽  
pp. 338-342 ◽  
Author(s):  
O. Van Reeth ◽  
Y. Zhang ◽  
P.C. Zee ◽  
F.W. Turek
Keyword(s):  
Circadian Clock ◽  
Phase Shifting ◽  
Suprachiasmatic Nuclei

Ionic Currents of Isolated Retinal Pacemaker Neurons: Projected Daily Phase Differences and Selective Enhancement by a Phase-Shifting Neurotransmitter

1997 ◽  
Vol 77 (6) ◽  
pp. 3075-3084 ◽  
Author(s):  
Steven Barnes ◽  
Jon W. Jacklet
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Primary Culture ◽  
Voltage Clamp ◽  
Ionic Currents ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Pacemaker Neurons ◽  
Selective Enhancement ◽  
Phase Differences

Barnes, Steven and Jon W. Jacklet. Ionic currents of isolated retinal pacemaker neurons: projected daily phase differences and selective enhancement by a phase-shifting neurotransmitter. J. Neurophysiol. 77: 3075–3084, 1997. The eye of Aplysia expresses a robust circadian rhythm of neuronal activity. We dissociated the retinal cells in primary culture and studied isolated pacemaker neurons to identify ionic currents that may have roles in the circadian clock mechanism. Individual neurons were studied with perforated-patch whole cell recording techniques in current- and voltage-clamp modes. Pacemaker neurons had resting potentials near −40 mV and, if neurites had grown out, produced spontaneous action potentials in darkness at <1 Hz. Depolarizing current injections increased the rate of action potential firing. Hyperpolarizing current injections were followed by slowly decaying (1–3 s) afterhyperpolarizations. Four ionic currents were characterized under voltage-clamp, including a Ca current ( I Ca), a voltage-gated potassium current ( I KV), an A current ( I A), and a hyperpolarization-activated Cl current ( I Cl). I Cl was only seen using Cl−-filled electrodes when high concentrations of Cl− diffused from the electrode and is therefore unlikely to be important under physiological conditions. The magnitude of I KV was significantly larger during the projected zeitgeber predawn phase than during the postdawn phase, whereas the magnitude of I A was constant at these circadian phases, suggesting that only I KV is controlled by the circadian clock. Serotonin increased I KV by 29%, consistent with reports that serotonin suppresses optic nerve activity and phase shifts the circadian rhythm recorded from the intact eye. The enhancement of I KV likely contributes to membrane hyperpolarization, and it may be required for phase shifting. The phase-dependent changes in I KV provide evidence that each retinal pacemaker neuron contains a circadian clock, but confirmation must await further recordings made from individual pacemaker neurons that are isolated completely from all other cells in primary culture. From the present experiments, it appears that I KV is controlled by the circadian clock, in part, and it may be a required element in the pathway that is activated during serotonin-induced phase shifts.

scholarly journals cGMP induces phase shifts of a mammalian circadian pacemaker at night, in antiphase to cAMP effects

1989 ◽  
Vol 86 (17) ◽  
pp. 6812-6815 ◽  
Author(s):  
R A Prosser ◽  
A J McArthur ◽  
M U Gillette
Keyword(s):  
Circadian Clock ◽  
Brain Slices ◽  
Phase Shifts ◽  
Suprachiasmatic Nuclei ◽  
Daily Cycle ◽  
Subjective Night ◽  
Camp And Cgmp ◽  
Diurnal Period ◽  
Nocturnal Period

The suprachiasmatic nuclei (SCN) of mammals contain a circadian clock that synchronizes behavioral and physiological rhythms to the daily cycle of light and darkness. We have been probing the biochemical substrates of this endogenous pacemaker by examining the ability of treatments affecting cyclic nucleotide-dependent pathways to induce changes in the phase of oscillation in electrical activity of rat SCN isolated in brain slices. Our previous work has shown that daytime treatments that stimulate cAMP-dependent pathways induce phase shifts of the SCN pacemaker in vitro but treatments during the subjective night are without effect. In this study we report that the phase of SCN oscillation is reset by treatments that stimulate cGMP-dependent pathways, but only during the subjective night. Thus, the nocturnal period of SCN sensitivity to cGMP is in antiphase to the diurnal period of sensitivity to cAMP. These results suggest that cAMP and cGMP affect the SCN pacemaker through separate biochemical pathways intrinsic to the SCN. These studies provide evidence that changing biochemical substrates within the SCN circadian clock may underlie some aspects of differential temporal sensitivity of mammals to resetting stimuli.

Phase-shifting effects of acute increases in activity on circadian locomotor rhythms in hamsters

1991 ◽  
Vol 261 (5) ◽  
pp. R1109-R1117 ◽  
Author(s):  
C. R. Wickland ◽  
F. W. Turek
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Running Wheel ◽  
Baseline Activity ◽  
Circadian Time ◽  
Activity State ◽  
Locomotor Rhythms ◽  
Running Wheels

Experiments were conducted in golden hamsters to examine the relationship between induced acute increases in locomotor activity and phase shifts in the circadian clock underlying the rhythm of activity. Injections of the short-acting benzodiazepine triazolam (TZ) 6 h before the onset of activity resulted in an acute increase in activity and a phase advance in the rhythm of activity; injections of TZ induced larger phase shifts in animals housed without running wheels than in those housed with wheels. Transfer to a cage with access to a running wheel for 1 h at different circadian times induced large phase advances (mean of 2 h) and small phase delays depending on the circadian time of transfer. Maximal mean phase advances resulted when animals were transferred to a cage with wheel 3 h before activity onset, and at this circadian time there was a significant correlation between the magnitude of the phase shift and the amount of increase over baseline activity for the first hour after transfer. These results indicate that access to a running wheel in animals housed without wheels can be a significant phase-shifting stimulus to the circadian clock and that the phase shifts induced by injection of TZ or transfer to a new cage with wheel are related to the activity state of the animal or to the amount of locomotor activity that is induced at particular times.

Aging alters feedback effects of the activity-rest cycle on the circadian clock

1992 ◽  
Vol 263 (4) ◽  
pp. R981-R986 ◽  
Author(s):  
O. Van Reeth ◽  
Y. Zhang ◽  
P. C. Zee ◽  
F. W. Turek
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Phase Shifts ◽  
Circadian System ◽  
Phase Shifting ◽  
Protein Synthesis Inhibitors ◽  
Feedback Effects ◽  
Age Related ◽  
Level Of Activity ◽  
Acute Change

Two different stimuli (i.e., benzodiazepines and dark pulses) inducing phase shifts in the circadian clock of young hamsters through changes in the level of activity do not induce phase shifts in old hamsters, despite the fact that these stimuli induce a similar acute change in locomotor activity in young and old animals. In contrast, old hamsters remain sensitive to the phase-shifting effects of stimuli clearly not associated with any change in locomotor activity (i.e., protein synthesis inhibitors or light). Thus the circadian system of old animals becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state of the animals. Previous age-related changes in circadian rhythmicity that have been observed in mammals, including humans, may be related to a weakened coupling between the activity-rest cycle and the circadian clock.

Neuropeptide Y phase advances the in vitro hamster circadian clock during the subjective day with no effect on phase during the subjective night

2000 ◽  
Vol 78 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Mary E Harrington ◽  
Kathryn M Schak
Keyword(s):  
Circadian Clock ◽  
Neuropeptide Y ◽  
Firing Rate ◽  
Phase Shifts ◽  
Suprachiasmatic Nuclei ◽  
Subjective Night ◽  
Circadian Change ◽  
Brain Slice Preparation ◽  
Spontaneous Firing Rate

The mammalian daily (circadian) clock is located in the suprachiasmatic nuclei of the hypothalamus. Clock function can be detected by the measurement of the circadian change in spontaneous firing rate of suprachiasmatic nuclei cells in a brain slice preparation in vitro. We investigated the effects of neuropeptide Y on this rhythm of firing rate in hamster suprachiasmatic nuclei neurons. Slices were prepared using standard techniques. On the 1st day in vitro, neuropeptide Y (200 ng/200 nL; 47 pmol) was applied as a microdrop to the suprachiasmatic nuclei region at various times. Spontaneous single-unit firing was measured for 6-12 h on the 2nd day in vitro. Peak firing rate in treated slices was compared with that of untreated control slices to measure phase shifts induced by the peptide. Neuropeptide Y induced phase advances of circa-3h when applied during the subjective day (ZT 2-10) but did not significantly alter phase when applied during the subjective night. The phase shifts to neuropeptide Y in the hamster tissue in vitro are similar in phase dependency and magnitude to shifts measured in vivo.Key words: circadian, neuropeptide Y, rhythm, suprachiasmatic.

Anterior paraventricular thalamus modulates light-induced phase shifts in circadian rhythmicity in rats

2002 ◽  
Vol 283 (4) ◽  
pp. R897-R904 ◽  
Author(s):  
Alberto Salazar-Juárez ◽  
Carolina Escobar ◽  
Raúl Aguilar-Roblero
Keyword(s):  
Circadian Rhythms ◽  
Thalamic Nucleus ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Suprachiasmatic Nuclei ◽  
Light Pulses ◽  
Subjective Night ◽  
Reciprocal Connections ◽  
Paraventricular Thalamus ◽  
Stimulation Of

The reciprocal connections between the paraventricular thalamic nucleus (PVT) and the suprachiasmatic nuclei suggest that PVT may participate in the regulation of circadian rhythms. We studied in rats the effect of lesions of the anterior and midposterior regions of the PVT on phase shifts of drinking circadian rhythm induced by light pulses at circadian times 6, 12, and 23, as well as the phase shifts produced by electrical or glutamatergic stimulation of the anterior PVT at the same circadian times. Lesion of the anterior PVT abolishes the advances induced by light during late subjective night, whereas midposterior PVT lesions did not affect the phase shifts. Electrical stimulation or glutamate injections in the anterior PVT mimic the phase-shifting effects of light pulses. These results indicate the participation of the anterior PVT as a modulator of entrainment of circadian rhythms to light.

Cycloheximide-induced phase shifting of circadian clock of Neurospora

1981 ◽  
Vol 241 (1) ◽  
pp. R31-R35 ◽  
Author(s):  
H. Nakashima ◽  
J. Perlman ◽  
J. F. Feldman
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Response Curve ◽  
Phase Response Curve ◽  
Phase Shifts ◽  
Phase Shifting ◽  
Normal Operation ◽  
Circadian Cycle ◽  
Response Curves ◽  
Inhibition Of Protein Synthesis

Cycloheximide (CHX), an inhibitor of cytosolic (80S) protein synthesis in eucaryotes, causes phase shifts of the circadian clock of Neurospora crassa when administered as 4-h pulses to cultures in liquid medium. Differential effects of the pulses at different phases of the circadian cycle were observed and plotted as a phase-response curve (PRC). Nearly all phase shifts observed were phase advances, with maximum sensitivity in the middle of the subjective day. Inhibition of protein synthesis by CHX was the same at both phases of the cycle. The PRC was the same at 20 and 25 degrees C. Dose-response curves for the effects of CHX on phase shifting and inhibition of protein synthesis were determined and showed a striking parallel in the responses of these two phenomena to CHX. These results support the view that synthesis of one or more proteins at specific phases of the circadian cycle is necessary for the normal operation of the circadian clock of Neurospora.

A serotonin agonist phase-shifts the circadian clock in the suprachiasmatic nuclei in vitro

1990 ◽  
Vol 534 (1-2) ◽  
pp. 336-339 ◽  
Author(s):  
Rebecca A. Prosser ◽  
Joseph D. Miller ◽  
H. Craig Heller
Keyword(s):  
Circadian Clock ◽  
Phase Shifts ◽  
Suprachiasmatic Nuclei ◽  
Serotonin Agonist
Sign in / Sign up

Export Citation Format

Share Document