Astrocytic control of extracellular GABA drives circadian timekeeping in the suprachiasmatic nucleus

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(21)

Published: May 15, 2023

The hypothalamic suprachiasmatic nucleus (SCN) is the master mammalian circadian clock. Its cell-autonomous timing mechanism, a transcriptional/translational feedback loop (TTFL), drives daily peaks of neuronal electrical activity, which in turn control behavior. Intercellular signals, mediated by neuropeptides, synchronize and amplify TTFL rhythms across circuit. SCN neurons are GABAergic, but role GABA circuit-level timekeeping unclear. How can GABAergic circuit sustain cycles when such increased firing should become inhibitory to network? To explore this paradox, we show that slices expressing sensor iGABASnFR demonstrate oscillation extracellular ([GABA]

Language: Английский

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Hypertension: Causes and Consequences of Circadian Rhythms in Blood Pressure

Circulation Research, Journal Year: 2024, Volume and Issue: 134(6), P. 810 - 832

Published: March 14, 2024

Hypertension is extremely common, affecting approximately 1 in every 2 adults globally. Chronic hypertension the leading modifiable risk factor for cardiovascular disease and premature mortality worldwide. Despite considerable efforts to define mechanisms that underlie hypertension, a potentially major component of disease, role circadian biology has been relatively overlooked both preclinical models humans. Although presence daily patterns observed from level genome whole organism, functional structural impact biological rhythms, including such as misalignment, remains poorly defined. Here, we review rhythms systems regulating blood pressure onset, progression, consequences hypertension. There an emphasis on relation vascular end-organ effects that, individually or combination, contribute complex phenotypes cognitive decline loss cardiac brain health. effective treatment options some individuals, control inadequate substantial portion hypertensive population. Greater insight into may form foundation novel more widely molecular therapies interventions help prevention, treatment, management its related pathophysiology.

Language: Английский

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Mutual coupling of neurons in the circadian master clock: what we can learn from fruit flies

Neurobiology of Sleep and Circadian Rhythms, Journal Year: 2025, Volume and Issue: 18, P. 100112 - 100112

Published: Jan. 18, 2025

Circadian master clocks in the brain consist of multiple neurons that are organized into populations with different morphology, physiology, and neuromessenger content presumably functions. In most animals, these distributed bilaterally, located close proximity to visual system, synchronized by eyes light-dark cycles environment. mammals cockroaches, each two consists a core region receives information from shell which output projections originate, whereas flies several other insects, lateral dorsal regions. all cases, morning evening clock seem exist, communication between them neurons, as well connection across hemispheres, is prerequisite for normal rhythmic function. Phenomena such rhythm splitting, internal desynchronization caused "decoupling" hemispheres or decoupling certain within one hemisphere. Since contain relatively few characterized at individual level, fly particularly suited study neurons. Here, we review organization bilateral brain, focus on synaptic paracrine connections comparison insects mammals.

Language: Английский

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Mechanisms for the biological activity of Gastrodia elata Blume and its constituents: A comprehensive review on sedative-hypnotic, and antidepressant properties

Phytomedicine, Journal Year: 2023, Volume and Issue: 123, P. 155251 - 155251

Published: Nov. 28, 2023

Language: Английский

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Mechanism of action of the Banxia–Xiakucao herb pair in sleep deprivation: New comprehensive evidence from network pharmacology, transcriptomics and molecular biology experiments

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 334, P. 118534 - 118534

Published: Nov. 1, 2024

Language: Английский

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Epigenetic control of circadian clocks by environmental signals

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

Language: Английский

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Peiyuan Ningshen-ointment alleviates learning and memory impairment induced by sleep deprivation through activating the cAMP/PKA signaling pathway

Phytomedicine, Journal Year: 2025, Volume and Issue: 142, P. 156469 - 156469

Published: Feb. 14, 2025

Language: Английский

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System-level time computation and representation in the suprachiasmatic nucleus revealed by large-scale calcium imaging and machine learning

Cell Research, Journal Year: 2024, Volume and Issue: 34(7), P. 493 - 503

Published: April 11, 2024

The suprachiasmatic nucleus (SCN) is the mammalian central circadian pacemaker with heterogeneous neurons acting in concert while each neuron harbors a self-sustained molecular clockwork. Nevertheless, how system-level SCN signals encode time of day remains enigmatic. Here we show that population-level Ca

Language: Английский

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

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(8), P. e3002281 - e3002281

Published: Aug. 29, 2023

The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting various types neurons and glial cells. Individual cells have autonomous molecular machinery cellular clock, but their intrinsic periods vary considerably. Here, we show that arginine vasopressin (AVP) set ensemble period SCN in vivo to control behavior rhythm. Artificial lengthening by deleting casein kinase 1 delta (CK1δ) whole lengthened free-running rhythm an extent similar CK1δ deletion specific AVP neurons. However, slices, PER2::LUC reporter rhythms these mice only partially transiently recapitulated lengthening, showing dissociation between shell core with instability shell. In contrast, calcium both vasoactive intestinal peptide (VIP) freely moving demonstrated stably behavioral upon neuron-specific deletion, without changing phase relationships each other. Furthermore, optogenetic activation acutely induced increase VIP vivo. These results indicate regulate other neurons, such as thus act primary determinant period.

Language: Английский

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Extensive soma‐soma plate‐like contact sites (ephapses) connect suprachiasmatic nucleus neurons

The Journal of Comparative Neurology, Journal Year: 2024, Volume and Issue: 532(6)

Published: June 1, 2024

The hypothalamic suprachiasmatic nucleus (SCN) is the central pacemaker for mammalian circadian rhythms. As such, this ensemble of cell-autonomous neuronal oscillators with divergent periods must maintain coordinated oscillations. To investigate ultrastructural features enabling such synchronization, 805 coronal ultrathin sections mouse SCN tissue were imaged electron microscopy and aligned into a volumetric stack, from which selected neurons within core reconstructed in silico. We found that clustered physically connected to each other via multiple large soma-to-soma plate-like contacts. In some cases, sliver glial process was interleaved. These contacts large, covering on average ∼21% apposing somata. It possible may be electrophysiological substrate synchronization between neurons. Such explain why maintained even when chemical synaptic transmission or electrical gap junctions blocked. ephaptic contact-mediated among nearby therefore contribute wave-like oscillations clock genes calcium signals observed SCN.

Language: Английский

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