-
Current Biology : CB Dec 2023Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body...
Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body temperature (Tb) during torpor is controlled by the brain, the specific neural circuits underlying these processes have not been comprehensively elucidated. In this study, we identify the neural circuits involved in torpor regulation by combining whole-brain mapping of torpor-activated neurons, cell-type-specific manipulation of neural activity, and viral tracing-based circuit mapping. We find that Trpm2-positive neurons in the preoptic area and Vgat-positive neurons in the dorsal medial hypothalamus are activated during torpor. Genetic silencing shows that the activity of either cell type is necessary to enter the torpor state. Finally, we show that these cells receive projections from the arcuate and suprachiasmatic nucleus and send projections to brain regions involved in thermoregulation. Our results demonstrate an essential role of hypothalamic neurons in the regulation of Tb and metabolic rate during torpor and identify critical nodes of the torpor regulatory network.
Topics: Hypothalamus; Torpor; Preoptic Area; Suprachiasmatic Nucleus; Brain
PubMed: 37992720
DOI: 10.1016/j.cub.2023.10.076 -
The European Journal of Neuroscience Jan 2020The mammalian circadian system is composed of a central clock situated in the hypothalamic suprachiasmatic nucleus (SCN) and peripheral clocks of each tissue and organ... (Review)
Review
The mammalian circadian system is composed of a central clock situated in the hypothalamic suprachiasmatic nucleus (SCN) and peripheral clocks of each tissue and organ in the body. While much has been learned about the pre- and postnatal development of the circadian system, there are still many unanswered questions about how and when cellular clocks start to tick and form the circadian system. Most SCN neurons contain a cell-autonomous circadian clock with individual specific periodicity. Therefore, the network of cellular oscillators is critical for the coherent rhythm expression and orchestration of the peripheral clocks by the SCN. The SCN is the only circadian clock entrained by an environmental light-dark cycle. Photic entrainment starts postnatally, and the SCN starts to function gradually as a central clock that controls physiological and behavioral rhythms during postnatal development. The SCN exhibits circadian rhythms in clock gene expression from the embryonic stage throughout postnatal life and the rhythm phenotypes remain basically unchanged. However, the disappearance of coherent circadian rhythms in cryptochrome-deficient SCN revealed changes in the SCN networks that occur in postnatal weeks 2-3. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by the vasoactive intestinal polypeptide and arginine vasopressin signaling depending on the period of postnatal development.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Cryptochromes; Photoperiod; Suprachiasmatic Nucleus
PubMed: 30589961
DOI: 10.1111/ejn.14318 -
Neuropharmacology Sep 2024Feeding, like many other biological functions, displays a daily rhythm. This daily rhythmicity is controlled by the circadian timing system of which the central master... (Review)
Review
Feeding, like many other biological functions, displays a daily rhythm. This daily rhythmicity is controlled by the circadian timing system of which the central master clock is located in the hypothalamic suprachiasmatic nucleus (SCN). Other brain areas and tissues throughout the body also display rhythmic functions and contain the molecular clock mechanism known as peripheral oscillators. To generate the daily feeding rhythm, the SCN signals to different hypothalamic areas with the lateral hypothalamus, paraventricular nucleus and arcuate nucleus being the most prominent. With respect to the rewarding aspects of feeding behavior, the dopaminergic system is also under circadian influence. However the SCN projects only indirectly to the different reward regions, such as the ventral tegmental area where dopamine neurons are located. In addition, high palatable, high caloric diets have the potential to disturb the normal daily rhythms of physiology and have been shown to alter for example meal patterns. Around a meal several hormones and peptides are released that are also under circadian influence. For example, the release of postprandial insulin and glucagon-like peptide following a meal depend on the time of the day. Finally, we review the effect of deletion of different clock genes on feeding behavior. The most prominent effect on feeding behavior has been observed in Clock mutants, whereas deletion of Bmal1 and Per1/2 only disrupts the day-night rhythm, but not overall intake. Data presented here focus on the rodent literature as only limited data are available on the mechanisms underlying daily rhythms in human eating behavior.
Topics: Animals; Feeding Behavior; Circadian Rhythm; Humans; Suprachiasmatic Nucleus
PubMed: 38795953
DOI: 10.1016/j.neuropharm.2024.110007 -
International Journal of Molecular... Jan 2022To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction... (Review)
Review
To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed "the self-regulation clock" and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the "clock" circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.
Topics: Biological Clocks; Cardiovascular System; Electroencephalography; Female; Gestational Age; Humans; Infant; Infant, Newborn; Pregnancy; Pyramidal Tracts; Suprachiasmatic Nucleus
PubMed: 35055184
DOI: 10.3390/ijms23020993 -
Current Biology : CB Oct 2023Short sleep is linked to disturbances in glucose metabolism and may induce a prediabetic condition. The biological clock in the suprachiasmatic nucleus (SCN) regulates...
Short sleep is linked to disturbances in glucose metabolism and may induce a prediabetic condition. The biological clock in the suprachiasmatic nucleus (SCN) regulates the glucose rhythm in the circulation and the sleep-wake cycle. SCN vasopressin neurons (SCN) control daily glycemia by regulating the entrance of glucose into the arcuate nucleus (ARC). Thus, we hypothesized that sleep delay may influence SCN neuronal activity. We, therefore, investigated the role of SCN when sleep is disrupted by forced locomotor activity. After 2 h of sleep delay, rats exhibited decreased SCN neuronal activity, a decrease in the glucose transporter GLUT1 expression in tanycytes lining the third ventricle, lowered glucose entrance into the ARC, and developed hyperglycemia. The association between reduced SCN neuronal activity and hyperglycemia in sleep-delayed rats was evidenced by injecting intracerebroventricular vasopressin; this increased GLUT1 immunoreactivity in tanycytes, thus promoting normoglycemia. Following sleep recovery, glucose levels decreased, whereas SCN neuronal activity increased. These results imply that sleep-delay-induced changes in SCN activity lead to glycemic impairment, inferring that disruption of biological clock function might represent a critical step in developing type 2 diabetes.
Topics: Rats; Animals; Glucose Transporter Type 1; Circadian Rhythm; Diabetes Mellitus, Type 2; Suprachiasmatic Nucleus; Sleep; Glucose; Hyperglycemia; Vasopressins
PubMed: 37725978
DOI: 10.1016/j.cub.2023.08.071 -
Handbook of Clinical Neurology 2021The circadian system, composed of the central autonomous clock, the suprachiasmatic nucleus (SCN), and systems of the body that follow the signals of the SCN,... (Review)
Review
The circadian system, composed of the central autonomous clock, the suprachiasmatic nucleus (SCN), and systems of the body that follow the signals of the SCN, continuously change the homeostatic set points of the body over the day-night cycle. Changes in the body's physiological state that do not agree with the time of the day feedback to the hypothalamus, and provide input to the SCN to adjust the condition, thus reaching another set point required by the changed conditions. This allows the adjustment of the set points to another level when environmental conditions change, which is thought to promote adaptation and survival. In fasting, the body temperature drops to a lower level only at the beginning of the sleep phase. Stressful conditions raise blood pressure relatively more during the active period than during the rest phase. Extensive, mostly reciprocal SCN interactions, with hypothalamic networks, induce these physiological adjustments by hormonal and autonomic control of the body's organs. More importantly, in addition to SCN's hormonal and autonomic influences, SCN induced behavior, such as rhythmic food intake, induces the oscillation of many genes in all tissues, including the so-called clock genes, which have an essential role as a transcriptional driving force for numerous cellular processes. Consequently, the light-dark cycle, the rhythm of the SCN, and the resulting rhythm in behavior need to be perfectly synchronized, especially where it involves synchronizing food intake with the activity phase. If these rhythms are not synchronous for extended periods of times, such as during shift work, light exposure at night, or frequent night eating, disease may develop. As such, our circadian system is a perfect illustration of how hypothalamic-driven processes depend on and interact with each other and need to be in seamless synchrony with the body's physiology.
Topics: Autonomic Nervous System; Circadian Clocks; Circadian Rhythm; Homeostasis; Humans; Hypothalamus; Suprachiasmatic Nucleus
PubMed: 34225965
DOI: 10.1016/B978-0-12-819975-6.00013-3 -
Handbook of Clinical Neurology 2021Vasopressin and oxytocin are primarily synthesized in the magnocellular supraoptic and paraventricular nuclei of the hypothalamus and transported to the posterior... (Review)
Review
Vasopressin and oxytocin are primarily synthesized in the magnocellular supraoptic and paraventricular nuclei of the hypothalamus and transported to the posterior pituitary. In the human, an extensive accessory magnocellular neuroendocrine system is present with contact to the posterior pituitary and blood vessels in the hypothalamus itself. Vasopressin and oxytocin are involved in social and behavioral functions. However, only few neocortical areas are targeted by vasopressinergic and oxytocinergic nerve fibers, which mostly project to limbic areas in the forebrain, where also their receptors are located. Vasopressinergic/oxytocinergic perikarya in the forebrain project to the brain stem and spinal cord targeting nuclei and areas involved in autonomic functions. Parvocellular neurons containing vasopressin are located in the suprachiasmatic nucleus and synchronize the activity of the pacemaker in this nucleus. From the suprachiasmatic nucleus fibers project to the parvocellular part of the paraventricular nucleus, where preautonomic neurons project to the intermediolateral nucleus in the thoracic spinal cord, from where the superior cervical ganglion is reached whose noradrenergic fibers terminate in the pineal gland to stimulate melatonin secretion at night. The pineal gland is also innervated by vasopressin- and oxytocin-containing fibers reaching the gland via the "central innervation" in the pineal stalk, which might be involve in an annual regulation of melatonin secretion.
Topics: Brain; Humans; Hypothalamus; Oxytocin; Paraventricular Hypothalamic Nucleus; Vasopressins
PubMed: 34225951
DOI: 10.1016/B978-0-12-820107-7.00002-1 -
Journal of Biosciences 2020The suprachiasmatic nucleus (SCN) that acts as the primary circadian pacemaker in mammals is responsible for orchestrating multiple circadian rhythms in every organism.... (Review)
Review
The suprachiasmatic nucleus (SCN) that acts as the primary circadian pacemaker in mammals is responsible for orchestrating multiple circadian rhythms in every organism. A network structure in the SCN composed of multiple types of neurons orchestrates the circadian rhythms. Despite speculations regarding the working of the clock, the molecular mechanisms governing it is far from clear. The molecular mechanism seems to be woven around the genes present and their linking with the neuromodulators. With the advancement in knowledge regarding the role of neuromodulators in the workings of the clock, especially that of Arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP), the entire picture of the mechanisms involved and therefore the importance of these neuromodulators has changed considerably. AVP seems to be very important for the functioning of the clock and its role has been well established based on the evidence available at present. Enormous research is going on to study the role of AVP and new roles are likely to be assigned to AVP in the execution of function in the SCN. Of late, there have been reports indicating linkage of AVP with jet lag in a positive way, suggesting vasopressin signalling as a possible remedy for ill effects and their improvement. Studies also show circadian rhythm disturbances in mood disorders and the same is related to AVP levels in the SCN. Various findings are thus in accordance with strong suggestions for a critical role for AVP in SCN function.
Topics: Animals; Arginine Vasopressin; Circadian Rhythm; Humans; Neurons; Signal Transduction; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins
PubMed: 33361631
DOI: No ID Found -
Chronobiology International Dec 2021Despite major developments in lung cancer investigations and the progress of innovative oncology treatments in recent decades, lung cancer continues to be the...
Despite major developments in lung cancer investigations and the progress of innovative oncology treatments in recent decades, lung cancer continues to be the predominant cause of cancer-related mortality globally, with over a million deaths each year. This highlights the urgent need to develop a deeper understanding of the current state of cancer care. At the environmental and cellular levels, circadian rhythms are closely associated with living organisms. In humans, the suprachiasmatic nucleus is the principal circadian pacemaker. Circadian gene feedback loops regulate the clock, connecting peripheral tissue metabolism, cell proliferation, DNA repair, and cell death to energy homeostasis, physical activity, and neurohormonal regulation at the organismal level. Endogenous circadian homeostasis has been frequently disturbed in modern civilizations, resulting in a higher risk of many disorders, including lung cancer. Despite major developments in lung cancer investigations and the progress of innovative oncology treatments in recent decades, lung cancer continues to be the predominant cause of cancer-related mortality globally, with over a million deaths each year. This highlights the urgent need to develop a deeper understanding of the current state of cancer care. At the environmental and cellular levels, circadian rhythms are closely associated with living organisms. In humans, the suprachiasmatic nucleus is the principal circadian pacemaker. Circadian gene feedback loops regulate the clock, connecting peripheral tissue metabolism, cell proliferation, DNA repair, and cell death to energy homeostasis, physical activity, and neurohormonal regulation at the organismal level. Endogenous circadian homeostasis has been frequently disturbed in modern civilizations, resulting in a higher risk of many disorders, including lung cancer. The mammalian circadian clock controls metabolism and cell division, and disruption of these processes may lead to cancer pathogenesis. Furthermore, circadian disturbance has recently been identified as a self-regulating cancer risk factor and is listed as a carcinogen. The theory that both somatic and systemic disturbances of circadian rhythms are related to a higher risk of lung cancer development and poor prognosis is addressed in this study. The chronotherapy principles hold much more promise for enhancing the lung cancer care options currently available. Developing a better understanding of the molecular interactions that control the physiological equilibrium between both the circadian rhythm and the cycle of cell division could significantly influence the development of novel treatments for lung cancer and other diseases.
Topics: Animals; Chronotherapy; Circadian Clocks; Circadian Rhythm; Humans; Lung Neoplasms; Suprachiasmatic Nucleus
PubMed: 34369216
DOI: 10.1080/07420528.2021.1963759 -
Pharmacopsychiatry May 2023Circadian rhythms are biological oscillations, that perpetuate themselves even in the absence of "zeitgebers" (external time cues), with a period of approximately...
Circadian rhythms are biological oscillations, that perpetuate themselves even in the absence of "zeitgebers" (external time cues), with a period of approximately 24 hours. The master pacemaker is the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is entrained by environmental factors, particularly light, to the 24-hour light-dark cycle by the Earth's rotation. Peripheral circadian oscillators, located in multiple cell types and tissues, are controlled by signals arising from the SCN and from the environment, particularly food intake, hormonal signals and body-temperature fluctuations. Circadian rhythmicity is observable in almost every cell of living organisms including humans and, for example in cell cultures, these rhythms persist even without the SCN 1 2.
Topics: Humans; Circadian Rhythm; CLOCK Proteins; Psychiatry; Suprachiasmatic Nucleus
PubMed: 37187176
DOI: 10.1055/a-2078-4905