High-Frequency Neuronal Bursting is Essential for Circadian and Sleep Behaviors inDrosophila DOI Creative Commons
Florencia Fernández-Chiappe, Lía Frenkel,

Carina Celeste Colque

et al.

Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 41(4), P. 689 - 710

Published: Dec. 1, 2020

Circadian rhythms have been extensively studied in Drosophila ; however, still little is known about how the electrical properties of clock neurons are specified. We performed a behavioral genetic screen through downregulation candidate ion channels lateral ventral (LNvs) and show that hyperpolarization-activated cation current I h important for behaviors LNvs influence: temporal organization locomotor activity, analyzed males, sleep, females. Using whole-cell patch clamp electrophysiology we demonstrate small (sLNvs) bursting neurons, necessary to achieve high-frequency firing pattern characteristic both types Since bursts has associated neuropeptide release, hypothesized would be communication. Indeed, herein fundamental recruitment pigment dispersing factor (PDF) filled dense core vesicles (DCVs) terminals at dorsal protocerebrum their timed hence coordination circadian behaviors. SIGNIFICANCE STATEMENT Ion transmembrane proteins with selective permeability specific charged particles. The rich repertoire parameters may gate opening state, such as voltage-sensitivity, modulation by second messengers kinetics, make this protein family determinant neuronal identity. channel structure evolutionary conserved between vertebrates invertebrates, making any discovery easily translatable. Through uncover roles rhythms, identified an player subset fruit fly. need fire action potentials mode peptide transport control behavior.

Language: Английский

Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms DOI Open Access
Erik D. Herzog, Tracey O. Hermanstyne, Nicola J. Smyllie

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2017, Volume and Issue: 9(1), P. a027706 - a027706

Published: Jan. 1, 2017

Erik D. Herzog1, Tracey Hermanstyne1, Nicola J. Smyllie2 and Michael H. Hastings2 1Department of Biology, Washington University in St. Louis, Missouri 63130-4899 2Division Neurobiology, MRC Laboratory Molecular Cambridge CB2 0QH, United Kingdom Correspondence: herzog{at}biology2.wustl.edu; mha{at}mrc-lmb.cam.ac.uk

Language: Английский

Citations

222
Off the Clock: From Circadian Disruption to Metabolic Disease DOI Open Access
Eléonore Maury

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(7), P. 1597 - 1597

Published: March 30, 2019

Circadian timekeeping allows appropriate temporal regulation of an organism’s internal metabolism to anticipate and respond recurrent daily changes in the environment. Evidence from animal genetic models humans under circadian misalignment (such as shift work or jet lag) shows that disruption rhythms contributes development obesity metabolic disease. Inappropriate timing food intake high-fat feeding also lead disruptions coordination physiology subsequently promote its pathogenesis. This review illustrates impact genetically environmentally induced molecular clock (at level brain peripheral tissues) interplay between system processes. Here, we discuss some mechanisms responsible for diet-induced desynchrony consider nutritional cues inter-organ communication, with a particular focus on communication organs brain. Finally, relay environmental information by signal-dependent transcription factors adjust gene oscillations. Collectively, better knowledge which function can be compromised will novel preventive therapeutic strategies other disorders arising desynchrony.

Language: Английский

Citations

118
NPAS4 regulates the transcriptional response of the suprachiasmatic nucleus to light and circadian behavior DOI
Pin Xu, Stefano Berto, Ashwinikumar Kulkarni

et al.

Neuron, Journal Year: 2021, Volume and Issue: 109(20), P. 3268 - 3282.e6

Published: Aug. 19, 2021

Language: Английский

Citations

67
Circadian regulation of membrane physiology in neural oscillators throughout the brain DOI
Jodi R. Paul, Jennifer A. Davis,

Lacy K. Goode

et al.

European Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 51(1), P. 109 - 138

Published: Jan. 11, 2019

Twenty-four-hour rhythmicity in physiology and behavior are driven by changes neurophysiological activity that vary across the light-dark rest-activity cycle. Although this neural code is most prominent neurons of primary circadian pacemaker suprachiasmatic nucleus (SCN) hypothalamus, there many other regions brain where region-specific function behavioral may be encoded electrical properties those neurons. In review, we explore existing evidence for molecular clocks and/or rhythms (i.e., 24 hr) outside SCN. addition, highlight ripe future investigation into critical role local oscillators. For example, cerebellum expresses over 2,000 gene transcripts, yet know very little about how regulation drives 24-hr coding responsible motor coordination. Finally, conclude with a discussion our understanding yield insight disease mechanisms which lead to novel chronotherapeutic strategies future.

Language: Английский

Citations

68
The Concept of Coupling in the Mammalian Circadian Clock Network DOI
Violetta Pilorz, Mariana Astiz, Keno Ole Heinen

et al.

Journal of Molecular Biology, Journal Year: 2020, Volume and Issue: 432(12), P. 3618 - 3638

Published: Jan. 10, 2020

Language: Английский

Citations

59
Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells DOI Creative Commons
Peter Quicke, Yilin Sun,

Mar Arias-García

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: Nov. 11, 2022

Abstract Cancer cells feature a resting membrane potential ( V m ) that is depolarized compared to normal cells, and express active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities ‘excitable’ tissues, relatively little known about cancer cell dynamics. Here high-throughput, cellular-resolution imaging reveals fluctuates dynamically several breast lines non-cancerous MCF-10A cells. We characterize fluctuations of hundreds human triple-negative MDA-MB-231 By quantifying Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identify four classes ranging from "noisy” “blinking/waving“. The exhibits spontaneous, transient hyperpolarizations inhibited by the voltage-gated sodium channel blocker tetrodotoxin, calcium-activated potassium inhibitors apamin iberiotoxin. comparatively static, but increase following treatment with transforming growth factor- β 1, canonical inducer epithelial-to-mesenchymal transition. These data suggest ability generate may be property hybrid epithelial-mesenchymal or those originated luminal progenitors.

Language: Английский

Citations

29
Aging and the clock: Perspective from flies to humans DOI Open Access
Aliza K. De Nobrega, Lisa C. Lyons

European Journal of Neuroscience, Journal Year: 2018, Volume and Issue: 51(1), P. 454 - 481

Published: Sept. 30, 2018

Abstract Endogenous circadian oscillators regulate molecular, cellular and physiological rhythms, synchronizing tissues organ function to coordinate activity metabolism with environmental cycles. The technological nature of modern society round‐the‐clock work schedules heavy reliance on personal electronics has precipitated a striking increase in the incidence sleep disorders. Circadian dysfunction contributes an increased risk for many diseases appears have adverse effects aging longevity animal models. From invertebrate organisms humans, synchronization system weakens age aggravating age‐related disorders pathologies. In this review, we highlight impacts reciprocal examples from Drosophila humans underscoring highly conserved these interactions. Additionally, review potential using reinforcement promote healthy mitigate Advancements medicine public health significantly human life span past century. With demographics countries worldwide shifting older population, there is critical need understand factors that shape aging. melanogaster , as model interactions, capacity facilitate rapid advancement research area provide mechanistic insights targeted investigations mammals.

Language: Английский

Citations

47
CBC‐Clock Theory of Life – Integration of cellular circadian clocks and cellular sentience is essential for cognitive basis of life DOI Creative Commons
František Baluška, Arthur S. Reber

BioEssays, Journal Year: 2021, Volume and Issue: 43(10)

Published: Aug. 11, 2021

Cellular circadian clocks represent ancient anticipatory systems which co-evolved with the first cells to safeguard their survival. Cyanobacteria one of most cells, having essentially invented photosynthesis together redox-based cellular some 2.7 billion years ago. Bioelectricity phenomena, based on redox homeostasis associated electron transfers in membranes and within protein complexes inserted excitable membranes, play important roles, not only anesthetics-sensitive sentience (awareness environment), but also coupling single into tissues organs unitary multicellular organisms. This integration basis is an essential feature cognitive CBC-Clock life.

Language: Английский

Citations

37
Intracellular Ion Control of WNK Signaling DOI
Elizabeth J. Goldsmith, Aylin R. Rodan

Annual Review of Physiology, Journal Year: 2022, Volume and Issue: 85(1), P. 383 - 406

Published: Oct. 13, 2022

The with no lysine (K) (WNK) kinases are an evolutionarily ancient group of atypical placement the catalytic and diverse physiological roles. Recent studies have shown that WNKs directly regulated by chloride, potassium, osmotic pressure. Here, we review discovery as chloride-sensitive discuss contexts in which chloride regulation has been demonstrated. These include kidney, pancreatic duct, neurons, inflammatory cells. We interdependent relationship pressure intracellular cell volume regulation. recent demonstration potassium speculate on possible Finally, structural mechanistic aspects ion discussed.

Language: Английский

Citations

26
An extra-clock ultradian brain oscillator sustains circadian timekeeping DOI Creative Commons
Min Tang, Li-Hui Cao, Yang Tian

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(35)

Published: Sept. 2, 2022

The master circadian clock generates 24-hour rhythms to orchestrate daily behavior, even running freely under constant conditions. Traditionally, the is considered self-sufficient in sustaining free-running timekeeping via its cell-autonomous molecular clocks and interneuronal communications within neural network. Here, we find a set of bona fide ultradian oscillators Drosophila brain that support timekeeping, despite being located outside circuit lacking gene expression. These extra-clock electrical (xCEOs) generate bursts, pacing widespread burst firing promoting rhythmic resting membrane potentials neurons parallel monosynaptic connections. Silencing xCEOs disrupts impairs cycling neuropeptide pigment dispersing factor, leading loss locomotor rhythms. Together, conclude not sustain behavior but requires additional endogenous inputs from oscillators.

Language: Английский

Citations

23