Uncovering the Roles of Clocks and Neural Transmission in the Resilience of Drosophila Circadian Network

Jaumouillé, Edouard; Koch, Rafael; Nagoshi, Emi

doi:10.3389/fphys.2021.663339

Cited by 6 publications

(4 citation statements)

References 66 publications

(131 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In conclusion, we suggest that a stably coupled, interconnected system of endogenous oscillators and clocks oscillating at defined frequency bands defines dynamic homeostatic setpoints of physiology and behavior. This systems-based concept comprising different time scales and different levels of complexity differs from the currently dominating hierarchical concepts of chronobiology (e.g., (Harvey et al, 2020;Rosbash, 2021;Patton and Hastings, 2023)) but appears to find increasing support (Hall, 2005;Stengl et al, 2015;Stengl and Arendt, 2016;Rojas et al, 2019;Jaumouillé et al, 2021;Stengl and Schröder, 2021;Yang et al, 2022;Heigwer et al, 2023). Furthermore, contrasting the current hypothesis (Hughes et al, 2009;Zhu et al, 2017;Ballance and Zhu, 2021) we propose an equally important role for plasma membrane associated PTFL clocks as compared to TTFL clocks associated with nuclear gene regulatory networks.…”

Section: Discussion: Our Novel Hypothesis Final Conclusion and Outlookcontrasting

confidence: 66%

Contribution of membrane-associated oscillators to biological timing at different timescales

Stengl¹,

Schneider²

2023

Preprint

View full text Add to dashboard Cite

Environmental rhythms have selected for endogenous clocks that predict regular environmental changes like the daily light-dark cycle. Endogenous clocks are based on positive feedforward and negative feedback loops that generate rhythms even under constant conditions. Autonomous coupling of oscillators is the basis of self-organized timing that determines the repetitive sequence of events of physiology and behavior while mechanisms of homeostatic plasticity serve to maintain and stabilize physiological and behavioral homeostasis. The best studied biological clocks are circadian clock neurons of insects and mammals. Their molecular clockwork in the nucleus consists of transcriptional and translational feedback loops (TTFLs). This clockwork generates ~24 h rhythms in clock gene expression entrained to the light-dark cycle. It is assumed to drive all circadian oscillations in clock neurons such as rhythms in membrane potential, second messenger levels, and neurotransmitter release, thereby controlling circadian rhythms in physiology and behavior. It is not discerned yet whether the membrane-bound rhythms are mere outputs of the TTFL clockwork or whether instead they are driven by an autonomous posttranscriptional feedback loop (PTFL) clockwork in the plasma membrane. Furthermore, next to circadian rhythms the plasma membrane generates rhythms on much faster or slower timescales. It is not understood whether and how these multiscale rhythms are linked. Based on our work in peripheral and central insect multiscale clock neurons, we hypothesize that the excitable plasma membrane constitutes an adaptive endogenous PTFL clockwork at multiple timescales. Multiscale membrane-associated rhythms are suggested to be coupled to, but not driven by, the TTFL clockwork in the nucleus. Furthermore, we suggest that negative feedback loops via protein kinases and phosphatases on the one hand provide for mechanisms of homeostatic plasticity that maintain physiological homeostasis, keeping the period of cellular clocks stable. On the other hand, they also serve as coupling factors and links between cellular oscillators and clocks at multiple time scales controlling the temporal sequence and/or synchronization of physiological and behavioral processes. Our novel hypothesis is up for challenge in future experiments in different species.

show abstract

Section: Discussion: Our Novel Hypothesis Final Conclusion and Outlookcontrasting

confidence: 66%

Contribution of membrane-associated oscillators to biological timing at different timescales

Stengl¹,

Schneider²

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…We suggest that a stably coupled, interconnected system of endogenous oscillators and clocks oscillating at defined frequency bands defines dynamic homeostatic setpoints of physiology and behavior. This systems-based concept comprising different time scales and different levels of complexity differs from the currently dominating hierarchical concepts of chronobiology (e.g., Harvey et al, 2020 ; Rosbash, 2021 ; Patton and Hastings, 2023 ) but appears to find increasing support ( Hall, 2005 ; Stengl et al, 2015 ; Stengl and Arendt, 2016 ; Rojas et al, 2019 ; Jaumouillé et al, 2021 ; Stengl and Schröder, 2021 ; Yang et al, 2022 ; Heigwer et al, 2023 ). Furthermore, contrasting the current hypothesis ( Hughes et al, 2009 ; Zhu et al, 2017 ; Ballance and Zhu, 2021 ) we propose an equally important role for plasma membrane associated PTFL clocks as compared to TTFL clocks associated with nuclear gene regulatory networks.…”

Section: Discussion: Our Novel Hypothesis Final Conclusion and Outlookmentioning

confidence: 78%

Contribution of membrane-associated oscillators to biological timing at different timescales

Stengl,

Schneider

2024

Front. Physiol.

View full text Add to dashboard Cite

Environmental rhythms such as the daily light-dark cycle selected for endogenous clocks. These clocks predict regular environmental changes and provide the basis for well-timed adaptive homeostasis in physiology and behavior of organisms. Endogenous clocks are oscillators that are based on positive feedforward and negative feedback loops. They generate stable rhythms even under constant conditions. Since even weak interactions between oscillators allow for autonomous synchronization, coupling/synchronization of oscillators provides the basis of self-organized physiological timing. Amongst the most thoroughly researched clocks are the endogenous circadian clock neurons in mammals and insects. They comprise nuclear clockworks of transcriptional/translational feedback loops (TTFL) that generate ∼24 h rhythms in clock gene expression entrained to the environmental day-night cycle. It is generally assumed that this TTFL clockwork drives all circadian oscillations within and between clock cells, being the basis of any circadian rhythm in physiology and behavior of organisms. Instead of the current gene-based hierarchical clock model we provide here a systems view of timing. We suggest that a coupled system of autonomous TTFL and posttranslational feedback loop (PTFL) oscillators/clocks that run at multiple timescales governs adaptive, dynamic homeostasis of physiology and behavior. We focus on mammalian and insect neurons as endogenous oscillators at multiple timescales. We suggest that neuronal plasma membrane-associated signalosomes constitute specific autonomous PTFL clocks that generate localized but interlinked oscillations of membrane potential and intracellular messengers with specific endogenous frequencies. In each clock neuron multiscale interactions of TTFL and PTFL oscillators/clocks form a temporally structured oscillatory network with a common complex frequency-band comprising superimposed multiscale oscillations. Coupling between oscillator/clock neurons provides the next level of complexity of an oscillatory network. This systemic dynamic network of molecular and cellular oscillators/clocks is suggested to form the basis of any physiological homeostasis that cycles through dynamic homeostatic setpoints with a characteristic frequency-band as hallmark. We propose that mechanisms of homeostatic plasticity maintain the stability of these dynamic setpoints, whereas Hebbian plasticity enables switching between setpoints via coupling factors, like biogenic amines and/or neuropeptides. They reprogram the network to a new common frequency, a new dynamic setpoint. Our novel hypothesis is up for experimental challenge.

show abstract

“…On the one hand, TeTxLC has been shown to directly interfere with synaptic transmission (Sweeney et al ., 1995) and neuropeptide release (Ding et al ., 2019). Silencing of LNv neurons using TeTxLC has been shown to have a modest effect on locomotor rhythmicity but severely disrupts morning anticipation in a manner that resembles the Pdf 01 mutation (Jaumouillé et al ., 2021; Kaneko et al ., 2000). On the other hand, the expression of Kir2.1 is known to reduce excitability by dampening electrical signals (Baines et al ., 2001).…”

Section: Discussionmentioning

confidence: 99%

Alcohol-induced sleep dysregulation in Drosophila is dependent on the neuropeptide PDF

Ramirez-Roman,

Fuenzalida-Uribe,

Ayala-Santiago

et al. 2024

Preprint

View full text Add to dashboard Cite

Alcohol exposure is known to trigger homeostatic adaptations in the brain that lead to the development of tolerance and dependence. These adaptations are also believed to be the root of a series of disturbances in sleep patterns that often manifest during the development of alcoholism and can have significant clinical and economic consequences. Unfortunately, the neuronal and genetic pathways that control the effects of alcohol on sleep are currently unknown, thus limiting our efforts to find effective treatment. In this study, we conduct a mechanistic exploration of the relationships between alcohol and sleep alterations using a Drosophila model system. We show that the genetic manipulation of the ventral lateral neurons (LNv) -a set of neurons known to control sleep in Drosophila- disrupts alcohol sensitivity and tolerance. Moreover, we show that alcohol exposure induces a series of alterations in sleep patterns that last for several days. Our results demonstrate that a single alcohol exposure promotes daytime sleep, alters the structure of sleep during the night, and reduces morning anticipatory behavior. In addition, we show that some of these alterations partially depend on the activity of the neuropeptide PDF, a key element in regulating sleep architecture. We propose that alcohol-induced sleep disruption stems from alterations in the activity of the PDF-releasing LNv neurons and that these alterations are similar to those that produce alcohol tolerance.

show abstract

Uncovering the Roles of Clocks and Neural Transmission in the Resilience of Drosophila Circadian Network

Cited by 6 publications

References 66 publications

Contribution of membrane-associated oscillators to biological timing at different timescales

Contribution of membrane-associated oscillators to biological timing at different timescales

Contribution of membrane-associated oscillators to biological timing at different timescales

Alcohol-induced sleep dysregulation in Drosophila is dependent on the neuropeptide PDF

Contact Info

Product

Resources

About