scholarly journals The M-current works in tandem with the persistent sodium current to set the speed of locomotion

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000738
Author(s):  
Jérémy Verneuil ◽  
Cécile Brocard ◽  
Virginie Trouplin ◽  
Laurent Villard ◽  
Julie Peyronnet-Roux ◽  
...  
Keyword(s):  
Computational Models ◽  
Sodium Current ◽  
Outward Current ◽  
Persistent Sodium Current ◽  
Pacemaker Neurons ◽  
Locomotor Rhythm ◽  
M Current ◽  
Frequency Regime ◽  
Locomotion Speed

The central pattern generator (CPG) for locomotion is a set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current (IM): a subthreshold noninactivating outward current blocked by 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone dihydrochloride (XE991) and enhanced by N-(2-chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA73). Immunostaining and mutant mice highlight an important role of Kv7.2-containing channels in mediating IM. Pharmacological modulation of IM regulates the emergence and the frequency regime of both pacemaker and CPG activities and controls the speed of locomotion. Computational models captured these results and showed how an interplay between IM and INaP endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how IM and INaP work in tandem to set the speed of locomotion.

scholarly journals It takes two to tango: M-current swings with the persistent sodium current to set the speed of locomotion

2020 ◽  
Author(s):  
Jeremy Verneuil ◽  
Cécile Brocard ◽  
Laurent Villard ◽  
Julie Peyronnet-Roux ◽  
Frédéric Brocard
Keyword(s):  
Computational Models ◽  
Sodium Current ◽  
Outward Current ◽  
Persistent Sodium Current ◽  
Pacemaker Neurons ◽  
Locomotor Rhythm ◽  
M Current ◽  
Frequency Regime ◽  
Locomotion Speed

SummaryThe central pattern generator (CPG) for locomotion is set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current, critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current (IM); a subthreshold non-inactivating outward current blocked by XE991 and enhanced by ICA73. Immunostaining and mutant mice highlight an important role of axonal Kv7.2 channels in mediating IM. Pharmacological modulation of IM regulates the emergence and the frequency regime of both pacemaker and CPG activities, and controls the speed of locomotion. Computational models captured these results and show howed an interplay between IM and INaP that endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how IM and INaP work in tandem to set the speed of locomotion.

scholarly journals Drosophila ATF-2 Regulates Sleep and Locomotor Activity in Pacemaker Neurons

2008 ◽  
Vol 28 (20) ◽  
pp. 6278-6289 ◽  
Author(s):  
Hideyuki Shimizu ◽  
Masami Shimoda ◽  
Terumi Yamaguchi ◽  
Ki-Hyeon Seong ◽  
Tomoo Okamura ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Locomotor Activity ◽  
Ectopic Expression ◽  
Physiological Role ◽  
Sleep Time ◽  
Pacemaker Neurons ◽  
Locomotor Rhythm ◽  
The Brain ◽  
Lateral Neurons

ABSTRACT Stress-activated protein kinases such as p38 regulate the activity of transcription factor ATF-2. However, the physiological role of ATF-2, especially in the brain, is unknown. Here, we found that Drosophila melanogaster ATF-2 (dATF-2) is expressed in large ventral lateral neurons (l-LNvs) and also, to a much lesser extent, in small ventral lateral neurons, the pacemaker neurons. Only l-LNvs were stained with the antibody that specifically recognizes phosphorylated dATF-2, suggesting that dATF-2 is activated specifically in l-LNvs. The knockdown of dATF-2 in pacemaker neurons using RNA interference decreased sleep time, whereas the ectopic expression of dATF-2 increased sleep time. dATF-2 knockdown decreased the length of sleep bouts but not the number of bouts. The ATF-2 level also affected the sleep rebound after sleep deprivation and the arousal threshold. dATF-2 negatively regulated locomotor activity, although it did not affect the circadian locomotor rhythm. The degree of dATF-2 phosphorylation was greater in the morning than at night and was enhanced by forced locomotion via the dp38 pathway. Thus, dATF-2 is activated by the locomotor while it increases sleep, suggesting a role for dATF-2 as a regulator to connect sleep with locomotion.

scholarly journals The critical role of persistent sodium current in hippocampal gamma oscillations

2020 ◽  
Vol 162 ◽  
pp. 107787
Author(s):  
Young-Jin Kang ◽  
Ethan M. Clement ◽  
Stefan L. Sumsky ◽  
Yangfei Xiang ◽  
In-Hyun Park ◽  
...  
Keyword(s):  
Sodium Current ◽  
Critical Role ◽  
Gamma Oscillations ◽  
Persistent Sodium Current

scholarly journals The Role of the Persistent Sodium Current in Epilepsy

2020 ◽  
pp. 153575972097397
Author(s):  
Eric R. Wengert ◽  
Manoj K. Patel
Keyword(s):  
Action Potentials ◽  
Cell Function ◽  
Sodium Current ◽  
Persistent Sodium Current ◽  
Sodium Ions ◽  
Pathogenic Role ◽  
The Past ◽  
Voltage Gated Sodium Channels ◽  
Total Sodium

Voltage-gated sodium channels (VGSCs) are foundational to excitable cell function: Their coordinated passage of sodium ions into the cell is critical for the generation and propagation of action potentials throughout the nervous system. The classical paradigm of action potential physiology states that sodium passes through the membrane only transiently (1-2 milliseconds), before the channels inactivate and cease to conduct sodium ions. However, in reality, a small fraction of the total sodium current (1%-2%) remains at steady state despite prolonged depolarization. While this persistent sodium current (INaP) contributes to normal physiological functioning of neurons, accumulating evidence indicates a particularly pathogenic role for an elevated INaP in epilepsy (reviewed previously 1 ). Due to significant advances over the past decade of epilepsy research concerning the importance of INaP in sodium channelopathies, this review seeks to summarize recent evidence and highlight promising novel anti-seizure medication strategies through preferentially targeting INaP.

Lung Computational Models and the Role of the Small Airways in Asthma

PEDIATRICS ◽  
2020 ◽  
Vol 146 (Supplement 4) ◽  
pp. S359.2-S360
Author(s):  
Jennilee Eppley ◽  
Todd Mahr
Keyword(s):  
Computational Models ◽  
Small Airways

LANDSLIDE RISK MANAGEMENT IN THE COASTAL ZONE OF THE KUIBYSHEV RESERVOIR DUE THE DESIGN OF HIGH-SPEED LINE "MOSCOW-KAZAN"

2017 ◽  
Author(s):  
Nikolai Petrov ◽  
Nikolai Petrov ◽  
Inna Nikonorova ◽  
Inna Nikonorova ◽  
Vladimir Mashin ◽  
...  
Keyword(s):  
High Speed ◽  
Computational Models ◽  
Stable State ◽  
Landslide Risk ◽  
Kuibyshev Reservoir ◽  
Stepped Surface ◽  
The Stability ◽  
Landslide Slope ◽  
The Village

High-speed railway "Moscow-Kazan" by the draft crosses the Volga (Kuibyshev reservoir) in Chuvashia region 500 m below the village of New Kushnikovo. The crossing plot is a right-bank landslide slope with a stepped surface. Its height is 80 m; the slope steepness -15-16o. The authors should assess the risk of landslides and recommend anti-landslide measures to ensure the safety of the future bridge. For this landslide factors have been analyzed, slope stability assessment has been performed and recommendations have been suggested. The role of the following factors have been analyzed: 1) hydrologic - erosion and abrasion reservoir and runoff role; 2) lithologyc (the presence of Urzhum and Northern Dvina horizons of plastically deformable rocks, displacement areas); 3) hydrogeological (the role of perched, ground and interstratal water); 4) geomorphological (presence of the elemental composition of sliding systems and their structure in the relief); 5) exogeodynamic (cycles and stages of landslide systems development, mechanisms and relationship between landslide tiers of different generations and blocks contained in tiers). As a result 6-7 computational models at each of the three engineering-geological sections were made. The stability was evaluated by the method “of the leaning slope”. It is proved that the slope is in a very stable state and requires the following measures: 1) unloading (truncation) of active heads blocks of landslide tiers) and the edge of the plateau, 2) regulation of the surface and groundwater flow, 3) concrete dam, if necessary.

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