Limb motion dictates how motor learning arises from arbitrary environmental dynamics

2013 ◽  
Vol 109 (10) ◽  
pp. 2466-2482 ◽  
Author(s):  
Gary C. Sing ◽  
Simon P. Orozco ◽  
Maurice A. Smith
Keyword(s):  
Motor Learning ◽  
Adaptive Response ◽  
Prolonged Exposure ◽  
High Amplitude ◽  
Internal Models ◽  
Body Motion ◽  
Dependent Manner ◽  
Adaptive Responses ◽  
Motion State ◽  
Systems Identification

A key idea in motor learning is that internal models of environmental dynamics are internally represented as functions of spatial variables including position, velocity, and acceleration of body motion. We refer to such a representation as motion dependent. The evidence for a motion-dependent representation is, however, primarily based on examination of the adaptation to motion-dependent dynamic environments. To more rigorously test this idea, we examined the adaptive response to perturbations that cannot be well approximated by motion-state: force-impulses—brief, high-amplitude pulses of force. The induced adaptation characterizes the impulse response of the system—a widely used technique for probing system dynamics in engineering systems identification. Here we examined the adaptive responses to two different force-impulse perturbations during human voluntary reaching movements. We found that although neither could be well approximated by motion-state ( R2< 0.18 in both cases), both perturbations induced single-trial adaptive responses that were ( R2> 0.87). Moreover, these responses were similar in shape to those induced by low-fidelity motion-based approximations of the force-impulses ( r > 0.88). Remarkably, we found that the motion dependence of the adaptive responses to force-impulses persisted, even after prolonged exposure ( R2> 0.95). During a 300-trial training period, trial-to-trial fluctuations in the position, velocity, and acceleration of motion accurately predicted trial-to-trial fluctuations in the adaptive response, and the adaptation gradually became more specific to the perturbation, but only via reorganization of the structure of the motion-dependent representation. These results indicate that internal models of environmental dynamics represent these dynamics in a motion-dependent manner, regardless of the nature of the dynamics encountered.

scholarly journals The dynamics of motor learning through the formation of internal models

2019 ◽  
Vol 15 (12) ◽  
pp. e1007118 ◽  
Author(s):  
Camilla Pierella ◽  
Maura Casadio ◽  
Ferdinando A. Mussa-Ivaldi ◽  
Sara A. Solla
Keyword(s):  
Motor Learning ◽  
Internal Models

Mitochondrial ROS initiate phosphorylation of p38 MAP kinase during hypoxia in cardiomyocytes

2002 ◽  
Vol 282 (6) ◽  
pp. L1324-L1329 ◽  
Author(s):  
Andre Kulisz ◽  
Ningfang Chen ◽  
Navdeep S. Chandel ◽  
Zuohui Shao ◽  
Paul T. Schumacker
Keyword(s):  
Kinase Inhibitor ◽  
Anion Channel ◽  
P38 Map Kinase ◽  
Proximal Region ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Dependent Manner ◽  
Adaptive Responses ◽  
Mitochondrial Ros ◽  
Mitogen Activated Protein

The p38 mitogen-activated protein kinase (MAPK) is phosphorylated in response to oxidative stress. Mitochondria in cardiomyocytes increase their generation of reactive oxygen species (ROS) during hypoxia (1–5% O2). These ROS participate in signal transduction pathways involved in adaptive responses, including ischemic preconditioning and gene transcription. The present study therefore tested the hypothesis that hypoxia induces p38 MAPK phosphorylation by augmenting mitochondrial ROS generation. In cardiomyocytes, phosphorylation of p38 was observed in a Po 2-dependent manner during hypoxia. This response was inhibited by rotenone, thenoyltrifluoroacetone, and myxothiazol, inhibitors of mitochondrial complexes I, II, and III, respectively. A similar inhibition was observed in the cells pretreated with anion channel inhibitor DIDS, which may block ROS release from mitochondria. During normoxia, increases in mitochondrial ROS elicited by azide (1–2 mM) or by the mitochondrial inhibitor antimycin A caused increased phosphorylation of p38. Brief treatment with exogenous H2O2 during normoxia also induced phosphorylation of p38 as hypoxia, but this effect was not abolished by myxothiazol or DIDS. The antioxidant N-acetyl-cysteine abolished the p38 response to hypoxia, presumably by scavenging H2O2, but the mitogen extracellular receptor kinase inhibitor PD-98059 did not inhibit p38 phosphorylation during hypoxia. Thus physiological hypoxia leads to p38 phosphorylation through a mechanism that requires electron flux in the proximal region of the mitochondrial electron transport chain, which suggests that either H2O2 or superoxide participates in activating that process.

scholarly journals Learning the same motor task twice impairs its retention in a time- and dose-dependent manner

2021 ◽  
Vol 288 (1942) ◽  
pp. 20202556
Author(s):  
R. Hamel ◽  
L. Dallaire-Jean ◽  
É. De La Fontaine ◽  
J. F. Lepage ◽  
P. M. Bernier
Keyword(s):  
Motor Learning ◽  
Refractory Period ◽  
Motor Task ◽  
Dependent Manner ◽  
Learning Session ◽  
Concurrent Learning ◽  
Performance Improvements ◽  
Dependent Process ◽  
Initial Learning ◽  
Dose Dependent

Anterograde interference emerges when two differing tasks are learned in close temporal proximity, an effect repeatedly attributed to a competition between differing task memories. However, recent development alternatively suggests that initial learning may trigger a refractory period that occludes neuroplasticity and impairs subsequent learning, consequently mediating interference independently of memory competition. Accordingly, this study tested the hypothesis that interference can emerge when the same motor task is being learned twice, that is when competition between memories is prevented. In a first experiment, the inter-session interval (ISI) between two identical motor learning sessions was manipulated to be 2 min, 1 h or 24 h. Results revealed that retention of the second session was impaired as compared to the first one when the ISI was 2 min but not when it was 1 h or 24 h, indicating a time-dependent process. Results from a second experiment replicated those of the first one and revealed that adding a third motor learning session with a 2 min ISI further impaired retention, indicating a dose-dependent process. Results from a third experiment revealed that the retention impairments did not take place when a learning session was preceded by simple rehearsal of the motor task without concurrent learning, thus ruling out fatigue and confirming that retention is impaired specifically when preceded by a learning session. Altogether, the present results suggest that competing memories is not the sole mechanism mediating anterograde interference and introduce the possibility that a time- and dose-dependent refractory period—independent of fatigue—also contributes to its emergence. One possibility is that learning transiently perturbs the homeostasis of learning-related neuronal substrates. Introducing additional learning when homeostasis is still perturbed may not only impair performance improvements, but also memory formation.

Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver

2006 ◽  
Vol 27 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Siew Hong Lam ◽  
Cecilia Lanny Winata ◽  
Yan Tong ◽  
Svetlana Korzh ◽  
Wen San Lim ◽  
...  
Keyword(s):  
Biological Networks ◽  
Adaptive Response ◽  
Iron Homeostasis ◽  
Specific Information ◽  
Adaptive Responses ◽  
Arsenic Metabolism ◽  
Genes Encoding ◽  
Shock Proteins ◽  
Zebrafish Liver

Arsenic is a prominent environmental toxicant and carcinogen; however, its molecular mechanism of toxicity and carcinogenicity remains poorly understood. In this study, we performed microarray-based expression profiling on liver of zebrafish exposed to 15 parts/million (ppm) arsenic [As(V)] for 8–96 h to identify global transcriptional changes and biological networks involved in arsenic-induced adaptive responses in vivo. We found that there was an increase of transcriptional activity associated with metabolism, especially for biosyntheses, membrane transporter activities, cytoplasm, and endoplasmic reticulum in the 96 h of arsenic treatment, while transcriptional programs for proteins in catabolism, energy derivation, and stress response remained active throughout the arsenic treatment. Many differentially expressed genes encoding proteins involved in heat shock proteins, DNA damage/repair, antioxidant activity, hypoxia induction, iron homeostasis, arsenic metabolism, and ubiquitin-dependent protein degradation were identified, suggesting strongly that DNA and protein damage as a result of arsenic metabolism and oxidative stress caused major cellular injury. These findings were comparable with those reported in mammalian systems, suggesting that the zebrafish liver coupled with the available microarray technology present an excellent in vivo toxicogenomic model for investigating arsenic toxicity. We proposed an in vivo, acute arsenic-induced adaptive response model of the zebrafish liver illustrating the relevance of many transcriptional activities that provide both global and specific information of a coordinated adaptive response to arsenic in the liver.

scholarly journals IL-33 and MRGPRX2-Triggered Activation of Human Skin Mast Cells—Elimination of Receptor Expression on Chronic Exposure, but Reinforced Degranulation on Acute Priming

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 341 ◽  
Author(s):  
Zhao Wang ◽  
Sven Guhl ◽  
Kristin Franke ◽  
Metin Artuc ◽  
Torsten Zuberbier ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Skin ◽  
Chronic Exposure ◽  
Prolonged Exposure ◽  
Receptor Expression ◽  
Dependent Manner ◽  
High Affinity ◽  
High Affinity Ige Receptor ◽  
G Protein Coupled ◽  
Positive Effect

Clinically relevant exocytosis of mast cell (MC) mediators can be triggered by high-affinity IgE receptor (FcεRI)-aggregation (allergic route) or by the so-called pseudo-allergic pathway elicited via MAS-related G protein-coupled receptor-X2 (MRGPRX2). The latter is activated by drugs and endogenous neuropeptides. We recently reported that FcεRI-triggered degranulation is attenuated when human skin mast cells are chronically exposed to IL-33. Here, we were interested in the regulation of the MRGPRX2-route. Chronic exposure of skin MCs to IL-33 basically eliminated the pseudo-allergic/neurogenic route as a result of massive MRGPRX2 reduction. This downregulation seemed to partially require c-Jun N-terminal Kinase (JNK), but not p38, the two kinases activated by IL-33 in skin MCs. Surprisingly, however, JNK had a positive effect on MRGPRX2 expression in the absence of IL-33. This was evidenced by Accell®-mediated JNK knockdown and JNK inhibition. In stark contrast to the dampening effect upon prolonged exposure, IL-33 was able to prime for increased degranulation by MRGPRX2 ligands when administered directly before stimulation. This supportive effect depended on p38, but not on JNK activity. Our data reinforce the concept that exposure length dictates whether IL-33 will enhance or attenuate secretion. IL-33 is, thus, the first factor to acutely enhance MRGPRX2-triggered degranulation. Finally, we reveal that p38, rarely associated with MC degranulation, can positively affect exocytosis in a context-dependent manner.

scholarly journals Relative roles of doxycycline and cation chelation in endothelial glycan shedding and adhesion of leukocytes

2011 ◽  
Vol 300 (2) ◽  
pp. H415-H422 ◽  
Author(s):  
Herbert H. Lipowsky ◽  
Rachna Sah ◽  
Anne Lescanic
Keyword(s):  
Prolonged Exposure ◽  
Divalent Cations ◽  
Surface Concentration ◽  
Matrix Metalloproteases ◽  
Permeability Barrier ◽  
Dependent Manner ◽  
Rolling Velocity ◽  
Mmp Inhibitor ◽  
Rat Mesentery ◽  
Subsequent Exposure

Leukocyte [white blood cell (WBC)] adhesion and shedding of glycans from the endothelium [endothelial cells (ECs)] in response to the chemoattractant f-Met-Leu-Phe (fMLP) has been shown to be attenuated by topical inhibition of matrix metalloproteases (MMPs) with doxycycline (Doxy). Since Doxy also chelates divalent cations, these responses were studied to elucidate the relative roles of cation chelation and MMP inhibition. WBC-EC adhesion, WBC rolling flux, and WBC rolling velocity were studied in postcapillary venules in the rat mesentery during superfusion with the cation chelator EDTA or Doxy. Shedding and accumulation of glycans on ECs, with and without fMLP, were quantified by the surface concentration of lectin (BS-1)-coated fluorescently labeled microspheres (FLMs) during constant circulating concentration. Without fMLP, low concentrations of EDTA (1–3 mM) increased FLM-EC sequestration due to disruption of the permeability barrier with prolonged exposure. In contrast, with 0.5 μM Doxy alone, FLM adhesion remained constant (i.e., no change in glycan content) on ECs, and WBC adhesion increased with prolonged superfusion. Without fMLP, EDTA did not affect firm WBC-EC adhesion but reduced WBC rolling flux in a dose-dependent manner. With fMLP, EDTA did not inhibit WBC adhesion, whereas Doxy did during the first 20 min of superfusion. Thus, the inhibition by Doxy of glycan (FLM) shedding and WBC adhesion in response to fMLP results from MMP inhibition, in contrast to cation chelation. With either Doxy or the MMP inhibitor GM-6001, WBC rolling velocity decreased by 50%, as in the case with fMLP, suggesting that MMP inhibition reduces sheddase activity, which increases the adhesiveness of rolling WBCs. These events increase the effective leukocrit on the venular wall and increase firm WBC-EC adhesion. Thus, MMP inhibitors have both a proadhesion effect by reducing sheddase activity while exerting an antiadhesion effect by inhibiting glycocalyx shedding and subsequent exposure of adhesion molecules on the EC surface.

scholarly journals Unravelling the Potential Cytotoxic Effects of Metal Oxide Nanoparticles and Metal(Loid) Mixtures on A549 Human Cell Line

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 447
Author(s):  
Fernanda Rosário ◽  
Maria João Bessa ◽  
Fátima Brandão ◽  
Carla Costa ◽  
Cláudia B. Lopes ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Prolonged Exposure ◽  
Titanium Dioxide Nanoparticles ◽  
Metal Oxide Nanoparticles ◽  
A549 Cells ◽  
Water Soluble ◽  
Oxide Nanoparticles ◽  
Dependent Manner ◽  
Thiazolyl Blue Tetrazolium Bromide ◽  
Cell Cycle Alterations

Humans are typically exposed to environmental contaminants’ mixtures that result in different toxicity than exposure to the individual counterparts. Yet, the toxicology of chemical mixtures has been overlooked. This work aims at assessing and comparing viability and cell cycle of A549 cells after exposure to single and binary mixtures of: titanium dioxide nanoparticles (TiO2NP) 0.75–75 mg/L; cerium oxide nanoparticles (CeO2NP) 0.75–10 μg/L; arsenic (As) 0.75–2.5 mg/L; and mercury (Hg) 5–100 mg/L. Viability was assessed through water-soluble tetrazolium (WST-1) and thiazolyl blue tetrazolium bromide (MTT) (24 h exposure) and clonogenic (seven-day exposure) assays. Cell cycle alterations were explored by flow cytometry. Viability was affected in a dose- and time-dependent manner. Prolonged exposure caused inhibition of cell proliferation even at low concentrations. Cell-cycle progression was affected by TiO2NP 75 mg/L, and As 0.75 and 2.5 μg/L, increasing the cell proportion at G0/G1 phase. Combined exposure of TiO2NP or CeO2NP mitigated As adverse effects, increasing the cell surviving factor, but cell cycle alterations were still observed. Only CeO2NP co-exposure reduced Hg toxicity, translated in a decrease of cells in Sub-G1. Toxicity was diminished for both NPs co-exposure compared to its toxicity alone, but a marked toxicity for the highest concentrations was observed for longer exposures. These findings prove that joint toxicity of contaminants must not be disregarded.

scholarly journals Elevated Radiation Exposure Associated With Above Surface Flat Detector Mini C-Arm Use

Hand ◽  
2017 ◽  
Vol 14 (4) ◽  
pp. 565-569
Author(s):  
Dennis P. Martin ◽  
Talia Chapman ◽  
Christopher Williamson ◽  
Brian Tinsley ◽  
Asif M. Ilyas ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Prolonged Exposure ◽  
Background Radiation ◽  
Image Intensifier ◽  
Body Part ◽  
Operating Table ◽  
Dependent Manner ◽  
Body Parts ◽  
Flat Detector ◽  
Dose Dependent

Background: This study aims to test the hypothesis that: (1) radiation exposure is increased with the intended use of Flat Surface Image Intensifier (FSII) units above the operative surface compared with the traditional below-table configuration; (2) this differential increases in a dose-dependent manner; and (3) radiation exposure varies with body part and proximity to the radiation source. Methods: A surgeon mannequin was seated at a radiolucent hand table, positioned for volar distal radius plating. Thermoluminescent dosimeters measured exposure to the eyes, thyroid, chest, hand, and groin, for 1- and 15-minute trials from a mini C-arm FSII unit positioned above and below the operating surface. Background radiation was measured by control dosimeters placed within the operating theater. Results: At 1-minute of exposure, hand and eye dosages were significantly greater with the flat detector positioned above the table. At 15-minutes of exposure, hand radiation dosage exceeded that of all other anatomic sites with the FSII in both positions. Hand exposure was increased in a dose-dependent manner with the flat detector in either position, whereas groin exposure saw a dose-dependent only with the flat detector beneath the operating table. Conclusions: These findings suggest that the surgeon’s hands and eyes may incur greater radiation exposure compared with other body parts, during routine mini C-arm FSII utilization in its intended position above the operating table. The clinical impact of these findings remains unclear, and future long-term radiation safety investigation is warranted. Surgeons should take precautions to protect critical body parts, particularly when using FSII technology above the operating with prolonged exposure time.

Effect of nintedanib, a triple angiokinase inhibitor, on EGFR and HER2 in colorectal cancer (CRC) models, and rational for its combinations with the ErbB family blocker afatinib.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 485-485
Author(s):  
Annette K. Larsen ◽  
Aimery de Gramont ◽  
Aude Batistella ◽  
Arnaud Afchain ◽  
Paul Mésange ◽  
...  
Keyword(s):  
Side Effects ◽  
Prolonged Exposure ◽  
Synergistic Effects ◽  
Angiogenesis Inhibitor ◽  
Synergistic Activity ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Erbb Family ◽  
Combination Methods ◽  
Erbb Family Blocker

485 Background: We have recently shown that combinations of afatinib, a pan-HER/ErbB blocker, and nintedanib, a triple angiokinase (VEGFR, FGFR, PDGFR) inhibitor show synergistic activity in CRC models (Poindessous et al., Clin Cancer Res. 17:6522, 2011). However, the mechanistic basis for the synergistic effects of the combination is incompletely understood. EGFR is activated following exposure to a wide variety of therapeutic modalities including ionizing irradiation and irinotecan. We speculated that nintedanib exposure could also activate EGFR signaling which might explain the synergistic activity of the combination. Methods: Mice with human CRC xenografts were treated with nintedanib and afatinib alone or in combination and the influence on tumor growth, viability and the presence of phosphorylated HER family members was determined. Different scheduling regimens were explored to identify an administration schedule which combined optimal antitumor activity with minimal toxic side effects. Results: We here show that nintedanib treatment results in activation of EGFR and HER2 in multiple CRC xenograft models in a dose-dependent manner. Among the different regimens tested, continuous nintedanib with administration of afatinib every second week proved almost as efficient as continuous administration of the two agents together and was less toxic. Finally, nintedanib plus afatinib was superior to nintedanib alone in three different tumor xenografts with mutant KRAS. Conclusions: We here report that prolonged exposure to nintedanib, a small molecule angiogenesis inhibitor, is accompanied by activation of EGFR and HER2. Accordingly, afatinib, an ErbB family blocker, was synergistic with nintedanib. We subsequently identified a novel regimen for optimizing the antitumor effects of the combination with limited toxic side effects and showed that this regimen is active in four different CRC tumor models including three with mutant KRAS. These findings provide a rationale for clinical trials of the two small molecules, even in patients with mutant KRAS.

scholarly journals DNA Microarray Analyses of the Long-Term Adaptive Response of Escherichia coli to Acetate and Propionate

2003 ◽  
Vol 69 (3) ◽  
pp. 1759-1774 ◽  
Author(s):  
T. Polen ◽  
D. Rittmann ◽  
V. F. Wendisch ◽  
H. Sahm
Keyword(s):  
Escherichia Coli ◽  
Dna Microarray ◽  
Adaptive Response ◽  
Carbon Sources ◽  
Short Chain Fatty Acids ◽  
Adaptive Responses ◽  
General Stress Response ◽  
E Coli ◽  
Short Term Exposure

ABSTRACT In its natural environment, Escherichia coli is exposed to short-chain fatty acids, such as acetic acid or propionic acid, which can be utilized as carbon sources but which inhibit growth at higher concentrations. DNA microarray experiments revealed expression changes during exponential growth on complex medium due to the presence of sodium acetate or sodium propionate at a neutral external pH. The adaptive responses to acetate and propionate were similar and involved genes in three categories. First, the RNA levels for chemotaxis and flagellum genes increased. Accordingly, the expression of chromosomal fliC′-′lacZ and flhDC′-′lacZ fusions and swimming motility increased after adaptation to acetate or propionate. Second, the expression of many genes that are involved in the uptake and utilization of carbon sources decreased, indicating some kind of catabolite repression by acetate and propionate. Third, the expression of some genes of the general stress response increased, but the increases were more pronounced after short-term exposure for this response than for the adaptive response. Adaptation to propionate but not to acetate involved increased expression of threonine and isoleucine biosynthetic genes. The gene expression changes after adaptation to acetate or propionate were not caused solely by uncoupling or osmotic effects but represented specific characteristics of the long-term response of E. coli to either compound.

Sign in / Sign up

Export Citation Format

Share Document