Inputs and Outputs of the Mammalian Circadian Clock

Starnes, Ashley N.

doi:10.3390/biology12040508

Cited by 20 publications

(17 citation statements)

References 214 publications

(252 reference statements)

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“…Our analyses reveal that extrinsic light input from the photoreceptor cells of the compound eyes, HB eyelets, and ocelli to the clock neurons is largely indirect, with the former two transmitting light inputs via aMe neurons. This situation may appear to be different from mammals where intrinsically photosensitive retinal ganglion cells in the retina project directly through the retinohypothalamic tract onto the SCN neurons (Figure 8) (Starnes and Jones, 2023). However, even the mammalian clock receives indirect photoreceptor inputs from rods and cones via bipolar cells and retinal ganglion cells.…”

Section: Light and Other Inputs To Drosophila And Vertebrate Circadia...mentioning

confidence: 94%

Synaptic connectome of theDrosophilacircadian clock

Reinhard,

Fukuda,

Manoli

et al. 2023

Preprint

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The circadian clock of animals regulates various physiological and behavioral processes in anticipation of, and adaptation to, daily environmental fluctuations. Consequently, the circadian clock and its output pathways play a pivotal role in maintaining homeostasis and optimizing daily functioning. To obtain novel insights into how diverse rhythmic physiology and behaviors are orchestrated, we have generated the first comprehensive connectivity map of an animal circadian clock using theDrosophilaFlyWire brain connectome. We reveal hitherto unknown extensive contralateral synaptic connectivity between the clock neurons, which might contribute to the robustness of the clock by synchronizing clock neurons across the two hemispheres. In addition, we discover novel direct and indirect light input pathways to the clock neurons that could facilitate clock entrainment. Intriguingly, we observe sparse monosynaptic connectivity between clock neurons and downstream higher-order brain centers and neurosecretory cells known to regulate several behaviors and physiology. Therefore, we integrated single-cell transcriptomic analysis and receptor mapping to additionally decipher paracrine peptidergic signaling between clock neurons and with neurosecretory cells. Our analyses identified additional novel neuropeptides expressed in clock neurons and suggest that peptidergic signaling greatly enriches the interconnectivity within the clock network. Neuropeptides also form the basis of output pathways which regulate rhythmic hormonal signaling. TheDrosophilacircadian clock and neurosecretory center connectomes provide the framework to understand more complex clock and hormonal networks, respectively, as well as the rhythmic processes regulated by them.

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Section: Light and Other Inputs To Drosophila And Vertebrate Circadia...mentioning

confidence: 94%

Synaptic connectome of theDrosophilacircadian clock

Reinhard,

Fukuda,

Manoli

et al. 2023

Preprint

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“…In mammals, when falling asleep, ipRGC cells activate the SCN and its output neurohumoral signals switch the metabolic mode of the pineal gland [6,22,[33][34][35]. Increases in the blood and CSF, the content of melatonin, serotonin, norepinephrine and other neurotransmitters, provide switching the homeostasis of the cerebral cortex and hydrodynamics of CSF to the glymphatic system mode.…”

Section: Physiological Correlationsmentioning

confidence: 99%

“…Genetically, the need for neocortical clearance reflects the specific lifestyle and physical characteristics of the animal's habitat. These features in mammals should correlate with the physiological parameters of sleep and the circadian rhythm control system, the signal chain of which includes the eyes with their photo-and thermoreceptors, the SCN, the pineal gland and the sleep center in the midbrain [18,22].…”

Section: Physiological Correlationsmentioning

confidence: 99%

“…At the same time, in the ganglion layer, ~1-2% of cells (ipRGC) are classified as specialthey synchronize their physiology and activity with the circadian «light-dark» cycle [18]. ipRGC cells have their own photopigment, melanopsin, different from rhodopsin, and are directly connected to the suprachiasmatic nucleus (SCN) of the hypothalamus [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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Thermo- and photoreceptors of eyes as regulators of circadian rhythm and glymphatic system

Kholmanskiy

2023

Preprint

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The dynamics of hydrogen bonds in bulk and hydrated water affected the activation energies of temperature dependence of ion currents of voltage-dependent channels that regulate communication and trophic bonds in the neuropil of the cortical parenchyma. The physics of minimizing of isobaric heat capacity of water made it possible to explain stabilization and functional optimization of thermodynamics of eyeball fluids at 34.5 C and human brain during sleep at 36.5 C. At these temperatures, thermoreceptors of cornea and cells of ganglionic layer of the retina, through connections with suprachiasmatic nucleus and pineal gland, switch brain metabolism from daytime to nighttime modes. The phylogenesis of circadian rhythm was reflected in dependence of duration of nighttime sleep of mammals on diameter of eyeball, mass of pineal gland, and density of neurons in parenchyma of cortex. The activity of all nerves of eyeball led to division of nocturnal sleep into slow and fast phases. These phases correspond to two modes of glymphatic system - electrochemical and dynamic. The first is responsible for relaxation processes of synaptic plasticity and chemical neutralization of toxins with participation of water and melatonin. Rapid eye movement and an increase in cerebral blood flow in second mode increase water exchange in parenchyma and flush out toxins into venous system.

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“…The suprachiasmatic nucleus (SCN) is the locus of the brain's clock, serving to synchronize physiological activities and behaviors to the local environment. Much work has identified both neural and diffusible output signals of the SCN though the former are better characterized (reviewed in Li et al, 2012;Morin, 2013;Patton and Hastings, 2018;Starnes and Jones, 2023). Functional diffusible signals of SCN transplants are effective even when the grafted tissue is encapsulated in a semipermeable polymer plastic that prevents neural fiber outgrowth, indicating that circadian activity rhythms can be sustained by diffusible signals (Silver et al, 1996).…”

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confidence: 99%

Vasculature of the Suprachiasmatic Nucleus: Pathways for Diffusible Output Signals

et al. 2023

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Transplant studies demonstrate unequivocally that the suprachiasmatic nucleus (SCN) produces diffusible signals that can sustain circadian locomotor rhythms. There is a vascular portal pathway between the SCN and the organum vasculosum of the lamina terminalis in mouse brain. Portal pathways enable low concentrations of neurosecretions to reach specialized local targets without dilution in the systemic circulation. To explore the SCN vasculature and the capillary vessels whereby SCN neurosecretions might reach portal vessels, we investigated the blood vessels (BVs) of the core and shell SCN. The arterial supply of the SCN differs among animals, and in some animals, there are differences between the 2 sides. The rostral SCN is supplied by branches from either the superior hypophyseal artery (SHpA) or the anterior cerebral artery or the anterior communicating artery. The caudal SCN is consistently supplied by the SHpA. The rostral SCN is drained by the preoptic vein, while the caudal is drained by the basal vein, with variations in laterality of draining vessels. In addition, several key features of the core and shell SCN regions differ: Median BV diameter is significantly smaller in the shell than the core based on confocal image measurements, and a similar trend occurs in iDISCO-cleared tissue. In the cleared tissue, whole BV length density and surface area density are significantly greater in the shell than the core. Finally, capillary length density is also greater in the shell than the core. The results suggest three hypotheses: First, the distinct arterial and venous systems of the rostral and caudal SCN may contribute to the in vivo variations of metabolic and neural activities observed in SCN networks. Second, the dense capillaries of the SCN shell are well positioned to transport blood-borne signals. Finally, variations in SCN vascular supply and drainage may contribute to inter-animal differences.

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Inputs and Outputs of the Mammalian Circadian Clock

Cited by 20 publications

References 214 publications

Synaptic connectome of theDrosophilacircadian clock

Synaptic connectome of theDrosophilacircadian clock

Thermo- and photoreceptors of eyes as regulators of circadian rhythm and glymphatic system

Vasculature of the Suprachiasmatic Nucleus: Pathways for Diffusible Output Signals

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