Circadian rhythm mechanism in the suprachiasmatic nucleus and its relation to the olfactory system.

Animals need sleep, and the suprachiasmatic nucleus, the center of the circadian rhythm, plays an important role in determining the timing of sleep. The main input to the suprachiasmatic nucleus is the retinohypothalamic tract, with additional inputs from the intergeniculate leaflet pathway, the serotonergic afferent from the raphe, and other hypothalamic regions. Within the suprachiasmatic nucleus, two of the major subtypes are vasoactive intestinal polypeptide (VIP)-positive neurons and arginine-vasopressin (AVP)-positive neurons.

Imeglimin profoundly affects the circadian clock in mouse embryonic fibroblasts.

Objective: Imeglimin is a novel antidiabetic drug structurally related to metformin. Metformin has been shown to modulate the circadian clock in rat fibroblasts. Accordingly, in the present study, we aimed to determine whether imeglimin can impact the circadian oscillator in mouse embryonic fibroblasts (MEFs).

In vivo recording of the circadian calcium rhythm in Prokineticin 2 neurons of the suprachiasmatic nucleus.

Prokineticin 2 (Prok2) is a small protein expressed in a subpopulation of neurons in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals. Prok2 has been implicated as a candidate output molecule from the SCN to control multiple circadian rhythms. Genetic manipulation specific to Prok2-producing neurons would be a powerful approach to understanding their function.

Action Sequence Learning Is Impaired in Genetically Modified Mice with the Suppressed GABAergic Transmission from the Thalamic Reticular Nucleus to the Thalamus.

The thalamic reticular nucleus (TRN) is a thin sheet of GABAergic neurons surrounding the thalamus, and it regulates the activity of thalamic relay neurons. The TRN has been reported to be involved in sensory gating, attentional regulation, and some other functions. However, little is known about the contribution of the TRN to sequence learning.

In vivo recording of suprachiasmatic nucleus dynamics reveals a dominant role of arginine vasopressin neurons in circadian pacesetting.

The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting of various types of neurons and glial cells. Individual cells have the autonomous molecular machinery of a cellular clock, but their intrinsic periods vary considerably. Here, we show that arginine vasopressin (AVP) neurons set the ensemble period of the SCN network in vivo to control the circadian behavior rhythm.

Clock cells ticking in summer.

In this issue of Neuron, Xie et al. highlight a role of cholecystokinin (CCK) neurons in the suprachiasmatic nucleus (SCN) central clock for tracking the onset of circadian activities, adapting circadian rhythms to long photoperiods, and regulating circadian phase resetting.

Desynchronization between Food Intake and Light Stimulations Induces Uterine Clock Quiescence in Female Mice.

Background: Dysmenorrhea is associated with breakfast skipping in young women, suggesting that fasting in the early active phase disrupts uterine functions.

Objectives: To investigate the possible involvement of the uterine clock system in fasting-induced uterine dysfunction, we examined core clock gene expressions in the uterus using a 28-h interval-fed mouse model.

Methods: Young female mice (8 wk of age) were divided into 3 groups: group I (ad libitum feeding), group II (time-restricted feeding, initial 4 h of the active period every day), and group III (time-restricted feeding for 8 h with a 28-h cycle).

SIK3-HDAC4 in the suprachiasmatic nucleus regulates the timing of arousal at the dark onset and circadian period in mice.

Mammals exhibit circadian cycles of sleep and wakefulness under the control of the suprachiasmatic nucleus (SCN), such as the strong arousal phase-locked to the beginning of the dark phase in laboratory mice. Here, we demonstrate that salt-inducible kinase 3 (SIK3) deficiency in gamma-aminobutyric acid (GABA)-ergic neurons or neuromedin S (NMS)-producing neurons delayed the arousal peak phase and lengthened the behavioral circadian cycle under both 12-h light:12-h dark condition (LD) and constant dark condition (DD) without changing daily sleep amounts. In contrast, the induction of a gain-of-function mutant allele of in GABAergic neurons exhibited advanced activity onset and a shorter circadian period.

l-Type amino acid transporter 1 in hypothalamic neurons in mice maintains energy and bone homeostasis.

Hypothalamic neurons regulate body homeostasis by sensing and integrating changes in the levels of key hormones and primary nutrients (amino acids, glucose, and lipids). However, the molecular mechanisms that enable hypothalamic neurons to detect primary nutrients remain elusive. Here, we identified l-type amino acid transporter 1 (LAT1) in hypothalamic leptin receptor-expressing (LepR-expressing) neurons as being important for systemic energy and bone homeostasis.

The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship.

The circadian rhythm, which is necessary for reproduction, is controlled by clock genes. In the mouse uterus, the oscillation of the circadian clock gene has been observed. The transcription of the core clock gene period () and cryptochrome () is activated by the heterodimer of the transcription factor circadian locomotor output cycles kaput () and brain and muscle Arnt-like protein-1 ().

Isolation of ferret astrocytes reveals their morphological, transcriptional, and functional differences from mouse astrocytes.

Astrocytes play key roles in supporting the central nervous system structure, regulating synaptic functions, and maintaining brain homeostasis. The number of astrocytes in the cerebrum has markedly increased through evolution. However, the manner by which astrocytes change their features during evolution remains unknown.

Female fertility does not require in suprachiasmatic nucleus neurons expressing arginine vasopressin, vasoactive intestinal peptide, or neuromedin-S.

Disruptions to the circadian system alter reproductive capacity, particularly in females. Mice lacking the core circadian clock gene, , are infertile and have evidence of neuroendocrine disruption including the absence of the preovulatory luteinizing hormone (LH) surge and enhanced responsiveness to exogenous kisspeptin. Here, we explore the role of in suprachiasmatic nucleus (SCN) neuron populations known to project to the neuroendocrine axis.

Vasopressin neurons in the paraventricular hypothalamus promote wakefulness via lateral hypothalamic orexin neurons.

The sleep-wakefulness cycle is regulated by complicated neural networks that include many different populations of neurons throughout the brain. Arginine vasopressin neurons in the paraventricular nucleus of the hypothalamus (PVH) regulate various physiological events and behaviors, such as body-fluid homeostasis, blood pressure, stress response, social interaction, and feeding. Changes in arousal level often accompany these PVH-mediated adaptive responses.

Paraventricular hypothalamic vasopressin neurons induce self-grooming in mice.

Self-grooming plays an essential role in hygiene maintenance, thermoregulation, and stress response. However, the neural populations involved in self-grooming remain largely unknown. The paraventricular hypothalamic nucleus (PVH) has been implicated in the regulation of self-grooming.

Cell Type-Specific Genetic Manipulation and Impaired Circadian Rhythms in Knock-In Mice.

The suprachiasmatic nucleus (SCN), the central circadian clock in mammals, is a neural network consisting of various types of GABAergic neurons, which can be differentiated by the co-expression of specific peptides such as vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP). VIP has been considered as a critical factor for the circadian rhythmicity and synchronization of individual SCN neurons. However, the precise mechanisms of how VIP neurons regulate SCN circuits remain incompletely understood.

Time-Restricted Feeding Regulates Circadian Rhythm of Murine Uterine Clock.

Background: Skipping breakfast is associated with dysmenorrhea in young women. This suggests that the delay of food intake in the active phase impairs uterine functions by interfering with circadian rhythms.

Objectives: To examine the relation between the delay of feeding and uterine circadian rhythms, we investigated the effects of the first meal occasion in the active phase on the uterine clock.

Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice.

Objective: Impaired circadian clocks can cause obesity, but their pathophysiological role in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energy expenditure.

Methods: Mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed.

GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior.

The suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals, is a network structure composed of multiple types of γ-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the roles of GABA-mediated signaling in the SCN network remain controversial. Here, we report noticeable impairment of the circadian rhythm in mice with a specific deletion of the vesicular GABA transporter in arginine vasopressin (AVP)-producing neurons.

[Neural Mechanisms Underlying the Central Circadian Clock of the Suprachiasmatic Nucleus].

Circadian rhythms are oscillations with an approximately 24-h period and appear in most of the physiological events of our body. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the central circadian clock in mammals and entrains to the environmental light/dark (day/night) cycle. Here, I briefly review the molecular, cellular, and anatomical structures of the SCN, present findings of recent studies on the differential roles of multiple neuropeptides and neuropeptide-expressing neurons in the SCN, and discuss the mechanisms of the SCN network.

Adolescent Dietary Habit-induced Obstetric and Gynecologic Disease (ADHOGD) as a New Hypothesis-Possible Involvement of Clock System.

There are growing concerns that poor dietary behaviors at young ages will increase the future risk of chronic diseases in adulthood. We found that female college students who skipped breakfast had higher incidences of dysmenorrhea and irregular menstruation, suggesting that meal skipping affects ovarian and uterine functions. Since dysmenorrhea is more prevalent in those with a past history of dieting, we proposed a novel concept that inadequate dietary habits in adolescence become a trigger for the subsequent development of organic gynecologic diseases.

The central circadian clock of the suprachiasmatic nucleus as an ensemble of multiple oscillatory neurons.

Circadian rhythms are oscillations with approximately 24-h period that appear in most of physiological events in our body. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the central circadian pacemaker in mammals and entrains to the environmental light/dark cycle. The SCN is a network structure composed of multiple types of γ-amino butyric acid (GABA)-ergic neurons and glial cells.

Dopamine D Receptor Deficiency Causes Stress Vulnerability through 5-HT Receptor Dysfunction in Serotonergic Neurons.

Mental disorders are caused by genetic and environmental factors. We here show that deficiency of an isoform of dopamine D receptor (DR), DR, causes stress vulnerability in mouse. This occurs through dysfunction of serotonin [5-hydroxytryptamine (5-HT)] 1A receptor (5-HTR) on serotonergic neurons in the mouse brain.

Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats.

Background: We previously reported that skipping breakfast is associated with menstrual disorders of female college students during postadolescent maturation.

Objective: In this study, we investigated the effects of meal timing during circadian cycle on the ovarian function using young female rats.

Methods: Considering that rats are nocturnally active, 8-wk-old female Wistar rats were classified into 3 groups: fed during the daytime only (nonactive phase), night-time only (active phase), or control group I (without time or calorie restriction, free access to a standard caloric diet, 20.

The Network Mechanism of the Central Circadian Pacemaker of the SCN: Do AVP Neurons Play a More Critical Role Than Expected?

The suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker in mammals and entrains to the environmental light/dark cycle. It is composed of multiple types of GABAergic neurons, and interneuronal communications among these neurons are essential for the circadian pacemaking of the SCN. However, the mechanisms underlying the SCN neuronal network remain unknown.

Glutamatergic neurons in the medial prefrontal cortex mediate the formation and retrieval of cocaine-associated memories in mice.

In drug addiction, environmental stimuli previously associated with cocaine use readily elicit cocaine-associated memories, which persist long after abstinence and trigger cocaine craving and consumption. Although previous studies suggest that the medial prefrontal cortex (mPFC) is involved in the expression of cocaine-addictive behaviors, it remains unclear whether excitatory and inhibitory neurons in the mPFC are causally related to the formation and retrieval of cocaine-associated memories. To address this issue, we used the designer receptors exclusively activated by designer drugs (DREADD) technology combined with a cocaine-induced conditioned place preference (CPP) paradigm.