The neural circadian system of mammals

2011 ◽  
Vol 49 ◽  
pp. 1-17 ◽  
Author(s):  
Hugh D. Piggins ◽  
Clare Guilding

Humans and other mammals exhibit a remarkable array of cyclical changes in physiology and behaviour. These are often synchronized to the changing environmental light–dark cycle and persist in constant conditions. Such circadian rhythms are controlled by an endogenous clock, located in the suprachiasmatic nuclei of the hypothalamus. This structure and its cells have unique properties, and some of these are reviewed to highlight how this central clock controls and sculpts our daily activities.

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5624-5634 ◽  
Author(s):  
Elizabeth S. Maywood ◽  
John S. O’Neill ◽  
Johanna E. Chesham ◽  
Michael H. Hastings

The secretion of hormones is temporally precise and periodic, oscillating over hours, days, and months. The circadian timekeeper within the suprachiasmatic nuclei (SCN) is central to this coordination, modulating the frequency of pulsatile release, maintaining daily cycles of secretion, and defining the time base for longer-term rhythms. This central clock is driven by cell-autonomous, transcriptional/posttranslational feedback loops incorporating Period (Per) and other clock genes. SCN neurons exist, however, within neural circuits, and an unresolved question is how SCN clock cells interact. By monitoring the SCN molecular clockwork using fluorescence and bioluminescence videomicroscopy of organotypic slices from mPer1::GFP and mPer1::luciferase transgenic mice, we show that interneuronal neuropeptidergic signaling via the vasoactive intestinal peptide (VIP)/PACAP2 (VPAC2) receptor for VIP (an abundant SCN neuropeptide) is necessary to maintain both the amplitude and the synchrony of clock cells in the SCN. Acute induction of mPer1 by light is, however, independent of VIP/VPAC2 signaling, demonstrating dissociation between cellular mechanisms mediating circadian control of the clockwork and those mediating its retinally dependent entrainment to the light/dark cycle. The latter likely involves the Ca2+/cAMP response elements of mPer genes, triggered by a MAPK cascade activated by retinal afferents to the SCN. In the absence of VPAC2 signaling, however, this cascade is inappropriately responsive to light during circadian daytime. Hence VPAC2-mediated signaling sustains the SCN cellular clockwork and is necessary both for interneuronal synchronization and appropriate entrainment to the light/dark cycle. In its absence, behavioral and endocrine rhythms are severely compromised.


1987 ◽  
Vol 253 (4) ◽  
pp. E401-E409
Author(s):  
D. R. Weaver ◽  
S. M. Reppert

The development of circadian rhythms was examined in a precocious rodent species, the spiny mouse. Spiny mouse pups born and reared in constant darkness expressed robust circadian rhythms in locomotor activity as early as day 5 of life. Free-running activity rhythms of pups born and reared in constant darkness were coordinated with the dam on the day of birth. Postnatal maternal influences on pup rhythmicity are minimal in this species, as pups fostered on the day of birth to dams whose circadian phases were opposite to the pups' original dams were coordinated with their original dams on the day of birth. Studies using 2-deoxy-D-[1-14C]-glucose autoradiography showed that there were synchronous (coordinated) rhythms in metabolic activity in the maternal and fetal suprachiasmatic nuclei, directly demonstrating prenatal coordination of maternal and fetal rhythmicity. Maternal-fetal coordination of circadian phase was not the result of direct entrainment of the fetuses to the environmental light-dark cycle. These results demonstrate that there is prenatal communication of circadian phase in this precocious species, without demonstrable postnatal maternal influences on pup circadian rhythmicity. Spiny mice therefore represent an important animal model in which circadian rhythms in the postnatal period can be used to precisely assess prenatal influences on circadian phase.


2010 ◽  
Vol 90 (3) ◽  
pp. 1063-1102 ◽  
Author(s):  
Diego A. Golombek ◽  
Ruth E. Rosenstein

Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since the period of this oscillation is of ∼24 h, to keep synchrony with the environment, circadian rhythms need to be entrained daily by means of Zeitgeber (“time giver”) signals, such as the light-dark cycle. Recent advances in the neurophysiology and molecular biology of circadian rhythmicity allow a better understanding of synchronization. In this review we cover several aspects of the mechanisms for photic entrainment of mammalian circadian rhythms, including retinal sensitivity to light by means of novel photopigments as well as circadian variations in the retina that contribute to the regulation of retinal physiology. Downstream from the retina, we examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction with SCN receptors and the resulting signal transduction pathways in suprachiasmatic neurons, as well as putative neuron-glia interactions. Finally, we describe and analyze clock gene expression and its importance in entrainment mechanisms, as well as circadian disorders or retinal diseases related to entrainment deficits, including experimental and clinical treatments.


2021 ◽  
Vol 15 ◽  
Author(s):  
Daisuke Ono ◽  
Ken-ichi Honma ◽  
Sato Honma

In mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Individual SCN cells exhibit intrinsic oscillations, and their circadian period and robustness are different cell by cell in the absence of cellular coupling, indicating that cellular coupling is important for coherent circadian rhythms in the SCN. Several neuropeptides such as arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) are expressed in the SCN, where these neuropeptides function as synchronizers and are important for entrainment to environmental light and for determining the circadian period. These neuropeptides are also related to developmental changes of the circadian system of the SCN. Transcription factors are required for the formation of neuropeptide-related neuronal networks. Although VIP is critical for synchrony of circadian rhythms in the neonatal SCN, it is not required for synchrony in the embryonic SCN. During postnatal development, the clock genes cryptochrome (Cry)1 and Cry2 are involved in the maturation of cellular networks, and AVP is involved in SCN networks. This mini-review focuses on the functional roles of neuropeptides in the SCN based on recent findings in the literature.


2005 ◽  
Vol 27 (6) ◽  
pp. 23-26
Author(s):  
Amanda-Jayne F. Carr ◽  
David Whitmore

The environmental light–dark cycle is one of the most reliable rhythmic signals, and many organisms have evolved a circadian (circa diem, ‘about a day’) system to co-ordinate biological processes with this predictable environmental change. These rhythms are endogenous and persist even in constant conditions, the light–dark cycle serving to synchronize these rhythms precisely to 24 hours. Genetic approaches have proved invaluable in increasing our understanding of the circadian clock. The ability to isolate a mutant with a defect in a rhythmic process is a very powerful method, which depends on no prior assumptions about the biological process under investigation. Consequently, Drosophila and the mouse have become the most powerful genetic models to study circadian rhythms in animals. The one alternative vertebrate genetic model system to the mouse is the zebrafish (Danio rerio).


Depression ◽  
2019 ◽  
pp. 390-396
Author(s):  
Raymond W. Lam

Chronobiology is the study of circadian rhythms that are present in many aspects of our daily health, from molecular to behavioral levels. Bright environmental light is known to synchronize the biological clock in the brain that regulates circadian hormonal and sleep–wake cycles. There is increasing evidence for disruption of circadian rhythms in the pathophysiology of major depressive disorder (MDD), especially in seasonal affective disorder (SAD). Chronobiological treatments that target the circadian system, including wake therapy (total sleep deprivation) and light therapy, have been studied for over four decades, with evidence supporting their efficacy in SAD and non-seasonal MDD, as well as in other psychiatric conditions. Wake and light therapies are useful additions to the clinical armamentarium for patients with MDD because of their noninvasive nature, low propensity for adverse events, rapid onset of effect, low cost, and ease of combining with other treatments for depression.


1981 ◽  
Vol 59 (7) ◽  
pp. 1326-1334 ◽  
Author(s):  
Martin Kavaliers ◽  
Donald M. Ross

Twilight and day-length portions of the light-dark cycle determine the seasonal course of (i) the phase relationship (ψ) between activity and the daily environmental light–dark cycle, (ii) the duration of activity (α), and (iii) the circadian period (τ) under constant darkness of the lake chub (Couesius plumbeus). With fish held under seasonally appropriate light–dark cycles with twilight (LD + t), the onset of diurnal activity occurred during dawn and its timing (ψonset) followed a bimodal annual pattern that was correlated with seasonal changes in the duration and physical characteristics of twilight. The end of activity occurred during dusk (ψoffset) and followed a unimodal annual pattern that was determined by day length. α followed a sigmoidal annual pattern under LD + t. The circadian period underwent significant seasonal changes with maximum and minimum τ values occurring during summer and winter, respectively. Fish that were entrained to rectangular light–dark cycles that excluded twilights (LD) failed to show any seasonal changes in ψ and τ and the sigmoidal relation between α and day length was absent.


2003 ◽  
Vol 285 (5) ◽  
pp. R939-R949 ◽  
Author(s):  
Christopher S. Colwell ◽  
Stephan Michel ◽  
Jason Itri ◽  
Williams Rodriguez ◽  
J. Tam ◽  
...  

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started ∼8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.


2007 ◽  
Vol 7 ◽  
pp. 203-212 ◽  
Author(s):  
Ann E. K. Kosobud ◽  
Andrea G. Gillman ◽  
Joseph K. Leffel ◽  
Norman C. Pecoraro ◽  
G. V. Rebec ◽  
...  

Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.


1984 ◽  
Vol 50 (1-3) ◽  
pp. 163-168 ◽  
Author(s):  
H.Elliott Albers ◽  
Craig F. Ferris

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