Paraventricular Thalamus Lesions Alter Circadian Period and Activity Distribution in the Blinded Rat

The paraventricular thalamic nucleus (PVT) is reciprocally connected with the suprachiasmatic nucleus, the mammalian circadian pacemaker. In this study, we examine the effects of PVT lesions on the free-running circadian rhythm of locomotor activity in the blinded, albino rat. In the blinded rat, lesions of the PVT cause a period lengthening of the free-running circadian rhythm and a change in the pattern of locomotor activity. In animals with complete PVT lesions, locomotor activity is concentrated in late subjective night as compared to the pre-lesion control. Our results suggest that the PVT participates in the regulation of suprachiasmatic pacemaker function and that this regulation may be modified by retinal input.     

Paraventricular Thalamus Lesions Alter Circadian Period and Activity Distribution in the Blinded Rat

The paraventricular thalamic nucleus (PVT) is reciprocally connected with the suprachiasmatic nucleus, the mammalian circadian pacemaker. In this study, we examine the effects of PVT lesions on the free-running circadian rhythm of locomotor activity in the blinded, albino rat. In the blinded rat, lesions of the PVT cause a period lengthening of the free-running circadian rhythm and a change in the pattern of locomotor activity. In animals with complete PVT lesions, locomotor activity is concentrated in late subjective night as compared to the pre-lesion control. Our results suggest that the PVT participates in the regulation of suprachiasmatic pacemaker function and that this regulation may be modified by retinal input.     

The mammalian circadian timing system: from gene expression to physiology

Many physiological processes in organisms from bacteria to man are rhythmic, and some of these are controlled by self-sustained oscillators that persist in the absence of external time cues. Circadian clocks are perhaps the best characterized biological oscillators and they exist in virtually all light-sensitive organisms. In mammals, they influence nearly all aspects of physiology and behavior, including sleep-wake cycles, cardiovascular activity, endocrinology, body temperature, renal activity, physiology of the gastro-intestinal tract, and hepatic metabolism. The master pacemaker is located in the suprachiasmatic nuclei, two small groups of neurons in the ventral part of the hypothalamus. However, most peripheral body cells contain self-sustained circadian oscillators with a molecular makeup similar to that of SCN (suprachiasmatic nucleus) neurons. This organization implies that the SCN must synchronize countless subsidiary oscillators in peripheral tissues, in order to coordinate cyclic physiology. In this review, we will discuss some recent studies on the structure and putative functions of the mammalian circadian timing system, but we will also point out some apparent inconsistencies in the currently publicized model for rhythm generation.     

How does the circadian clock send timing information to the brain?

This paper discusses circadian output in terms of the signaling mechanisms used by circadian pacemaker neurons. In mammals, the suprachiasmatic nucleus houses a clock controlling several rhythmic events. This nucleus contains one or more pacemaker circuits, and exhibits diversity in transmitter content and in axonal projections. In Drosophila, a comparable circadian clock is located among period -expressing neurons, a sub-set of which (called LN-vs) express the neuropeptide PDF. Genetic experiments indicate LN-vs are the primary pacemakers neurons controlling daily locomotion and that PDF is the principal circadian transmitter. Further definition of pacemaker properties in several model systems will provide a useful basis with which to describe circadian output mechanisms.     

Circadiane Uhren und Energiemetabolismus

Chrononutrition – circadian clocks and energy metabolism Genetically encoded endogenous clocks regulate 24‐hour rhythms of physiology and behavior. A central pacemaker residing in the suprachiasmatic nucleus synchronizes peripheral clocks found in all tissues with each other and with the external day‐night cycle. One function of circadian clocks is the regulation of energy metabolism via rhythmic activation of tissue‐specific clock‐controlled genes. In the liver, genes involved in glucose and lipid metabolism are regulated in this fashion, while in adipocytes, fatty acid release and adipokine secretion are controlled by the circadian clock. Disruption of circadian rhythms as seen, for example, in shift workers promotes the development of metabolic disorders such as obesity and type‐2 diabetes.     

The mammalian circadian clock shop.

In mammals, a master circadian pacemaker driving daily rhythms in behavior and physiology resides in the suprachiasmatic nucleus (SCN). The SCN contains multiple circadian oscillators that synchronize to environmental cycles and to each other in vivo. Rhythm production, an intracellular event, depends on more than eight identified genes. The period of the rhythms within the SCN also depends upon intercellular communication. Many other tissues also retain the ability to generate near 24 -h periodicities although their place in the organization of circadian timing is still unclear. This paper focuses on the tissue-, cellular- and molecular-level events that generate and entrain circadian rhythms in behavior in mammals and emphasizes the apparent differences between the SCN and peripheral oscillators.     

Acute exposure to 2G phase shifts the rat circadian timing system

The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cues (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination but exhibit a "free-running" condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral physiological systems that express these circadian parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.     

Internal rhythms in humans

Human physiology and behavior are characterized by a daily internal temporal dimension. This so-called circadian rhythmicity is present for almost all variables studied to date, persists in the absence of external cycles, and is synchronized to the external 24-h world by an internally generated circadian rhythm of light sensitivity. The light-sensitive circadian pacemaker, presumably also in humans located in the suprachiasmatic nucleus of the hypothalamus, drives the endogenous circadian component of rhythmicity for a number of variables including plasma melatonin, alertness, sleep propensity and sleep structure. Overt rhythmicity and the consolidation of vigilance states are generated by a fine-tuned interaction of this circadian process with other regulatory processes such as sleep homeostasis.     

Come together, right...now: synchronization of rhythms in a mammalian circadian clock

In mammals, the suprachiasmatic nuclei (SCN) of the hypothalamus act as a dominant circadian pacemaker, coordinating rhythms throughout the body and regulating daily and seasonal changes in physiology and behavior. This review focuses on the mechanisms that mediate synchronization of circadian rhythms between SCN neurons. Understanding how these neurons communicate as a network of circadian oscillators has begun to shed light on the adaptability and dysfunction of the brain's master clock.     

Mop3 is an essential component of the master circadian pacemaker in mammals

Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light-dark (LD) cycles is impaired and activity levels are reduced in Mop3-/- mice. Analysis of Period gene expression in the suprachiasmatic nucleus (SCN) indicates that these behavioral phenotypes arise from loss of circadian function at the molecular level. These results provide genetic evidence that MOP3 is the bona fide heterodimeric partner of mCLOCK. Furthermore, these data demonstrate that MOP3 is a nonredundant and essential component of the circadian pacemaker in mammals.     

Age-dependent effects of conditioning on cholinergic and vasopressin systems in the rat suprachiasmatic nucleus

Active shock avoidance was used to explore the impact of behavioural stimulation on the neurochemistry of the suprachiasmatic nucleus. We have found previously that the expression of muscarinic acetylcholine receptors in the suprachiasmatic nucleus of young rats was significantly enhanced 24 hours after fear conditioning. Here, we investigated whether this observation is age-dependent. We used 26 month-old Wistar rats with a deteriorated circadian system, and compared them with young rats (4 months of age) with an intact circadian system. Vasopressin, representing a major output system of the suprachiasmatic nucleus, was studied in addition to muscarinic receptors. Young rats showed a significant increase in immunostaining for muscarinic acetylcholine receptors 24 h after training, corroborating earlier observations. Aged rats did not show such an increase. In contrast, aged rats did show an increase in vasopressin immunoreactivity 24 h after fear conditioning, both at the level of content and cell number, while young rats did not reveal a significant rise. Thus, it seems that these two neurochemical systems in the suprachiasmatic nucleus are regulated independently. The results further demonstrate that the circadian pacemaker is influenced by fear conditioning in an age-dependent manner.     

The influence of neuronal electrical activity on the mammalian central clock metabolome

Metabolomics - Most organisms display circadian rhythms in physiology and behaviour. In mammals, these rhythms are orchestrated by the suprachiasmatic nucleus (SCN). Recently, several metabolites...     

Effects of the 5HT1A agonist/antagonist BMY 7378 on light-induced phase advances in hamster circadian activity rhythms during aging

The entrainment of some circadian rhythms in rodents and humans to the environmental light-dark cycle deteriorates during aging. Recent evidence suggests that the time-keeping ability of the circadian pacemaker maintains its endogenous period in both hamsters and humans. This suggests that any changes in the coupling between environmental cues and the circadian pacemaker are not due to changes in "clock speed," but rather due to a weakened coupling between the afferent systems relaying environmental information and the circadian pacemaker located in the suprachiasmatic nucleus. The suprachiasmatic nucleus receives serotonergic input from the raphe nuclei, and serotonergic 5HT1A,7 agonists have been reported to lose their circadian phase-adjusting efficacy during aging in hamsters. In the present study, the authors report the effects of a novel serotonergic agonist BMY 7378 on light-induced phase advances during aging in the hamster. The present report demonstrates that BMY 7378 is a highly efficacious chronobiotic that more than doubles the magnitude of light-induced phase shifts in hamster wheel-running activity rhythms. Light-induced phase advances in hamster wheel-running activity of at least 6 h following a single systemic dose of BMY 7378 are routinely observed. Furthermore, BMY 7378 potentiation of phase shifts is maintained in old hamsters, suggesting that BMY 7378 has a different site of activity than previously reported 5HT1A,7 agonists that have a diminished effect on circadian phase during aging.     

In vivo monitoring of circadian timing in freely moving mice

In mammals, the principal circadian pacemaker driving daily physiology and behavioral rhythms is located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The neural output of SCN is essential for the circadian regulation of behavioral activity. Although remarkable progress has been made in revealing the molecular basis of circadian rhythm generation within the SCN, the output pathways by which the SCN exert control over circadian rhythms are not well understood. Most SCN efferents target the subparaventricular zone (SPZ), which resides just dorsal to the SCN. This output pathway has been proposed as a major component involved in the outflow for circadian regulation. We have examined the downstream pathway of the central clock by means of multiunit neural activity (MUA) in freely moving mice. SCN neural activity is tightly coupled to environmental photic input and anticorrelated with MUA rhythm in the SPZ. In Clock mutant mice exhibiting attenuated circadian locomotor rhythmicity, MUA rhythmicity in the SCN and SPZ is similarly blunted. These results suggest that the SPZ plays a functional role in relaying circadian and photic signals to centers involved in generating behavioral activity.     

Emergence of circadian and photoperiodic system level properties from interactions among pacemaker cells

Daily patterns of behavior and physiology in animals in temperate zones often differ substantially between summer and winter. In mammals, this may be a direct consequence of seasonal changes of activity of the suprachiasmatic nucleus (SCN). The purpose of this study was to understand such variation on the basis of the interaction between pacemaker neurons. Computer simulation demonstrates that mutual electrical activation between pacemaker cells in the SCN, in combination with cellular electrical activation by light, is sufficient to explain a variety of circadian phenomena including seasonal changes. These phenomena are: self-excitation, that is, spontaneous development of circadian rhythmicity in the absence of a light-dark cycle; persistent rhythmicity in constant darkness, and loss of circadian rhythmicity in pacemaker output in constant light; entrainment to light-dark cycles; aftereffects of zeitgeber cycles with different periods; adjustment of the circadian patterns to day length; generation of realistic phase response curves to light pulses; and relative independence from day-to-day variation in light intensity. In the model, subsets of cells turn out to be active at specific times of day. This is of functional importance for the exploitation of the SCN to tune specific behavior to specific times of day. Thus, a network of on-off oscillators provides a simple and plausible construct that behaves as a clock with readout for time of day and simultaneously as a clock for all seasons.     

Cell Cultures of Rat Suprachiasmatic Nucleus: Circadian Oscillation of Vasopressin Release

A dissociated cell culture system has been developed for the suprachiasmatic nucleus (SCN), in which release of vasopressin showed a clear circadian oscillation. The oscillation peaked at early subjective day and appeared within one day in culture. This system may provide a valuable model for the study of cellular and molecular mechanisms of the mammalian circadian pacemaker.     

哺乳动物昼夜节律调节的神经基础——昼夜光感受器

哺乳动物昼夜光感受器为一组具有直接感光功能的特殊视网膜神经节细胞 ,其基本感光色素为黑视素 .昼夜光感受器具有直接、广谱和稳定感受昼夜光变化的功能特点 .昼夜光感受器的功能是通过导引作用 ,使下丘脑视交叉上核内的昼夜节律活动与外界明 暗周期变化同步