scholarly journals Minimal interplay between explicit knowledge, dynamics of learning and temporal expectations in different, complex uni- and multisensory contexts

2021 ◽  
Author(s):  
Felix Ball ◽  
Inga Spuerck ◽  
Toemme Noesselt
Keyword(s):  
Explicit Knowledge ◽  
Dependent Manner ◽  
Computational Learning ◽  
Complex Environments ◽  
Performance Improvements ◽  
Visual Distractor ◽  
Performance Accuracy ◽  
Behavioural Performance ◽  
Knowledge Dynamics ◽  
Time Point

AbstractWhile temporal expectations (TE) generally improve reactions to temporally predictable events, it remains unknown how the learning of temporal regularities (one time point more likely than another time point) and explicit knowledge about temporal regularities contribute to performance improvements; and whether any contributions generalise across modalities. Here, participants discriminated the frequency of diverging auditory, visual or audio-visual targets embedded in auditory, visual or audio-visual distractor sequences. Temporal regularities were manipulated run-wise (early vs. late target within sequence). Behavioural performance (accuracy, RT) plus measures from a computational learning model all suggest that learning of temporal regularities occurred but did not generalise across modalities, and that dynamics of learning (size of TE effect across runs) and explicit knowledge have little to no effect on the strength of TE. Remarkably, explicit knowledge affects performance—if at all—in a context-dependent manner: Only under complex task regimes (here, unknown target modality) might it partially help to resolve response conflict while it is lowering performance in less complex environments.

scholarly journals Minimal interplay between explicit knowledge, dynamics of learning and temporal expectations in different, complex uni- and multisensory contexts

2021 ◽  
Author(s):  
Felix Ball ◽  
Inga Spuerck ◽  
Toemme Noesselt
Keyword(s):  
Explicit Knowledge ◽  
Rule Learning ◽  
Dependent Manner ◽  
Complex Task ◽  
Computational Learning ◽  
Complex Environments ◽  
Performance Improvements ◽  
Performance Accuracy ◽  
Behavioural Performance ◽  
Knowledge Dynamics

AbstractWhile temporal expectations (TE) generally improve reactions to temporally predictable events, it remains unknown how temporal rule learning and explicit knowledge about temporal rules contribute to performance improvements and whether any contributions generalise across modalities. Here, participants discriminated the frequency of diverging auditory, visual or audiovisual targets embedded in auditory, visual or audiovisual distractor sequences. Temporal regularities were manipulated run-wise (early vs. late target within sequence). Behavioural performance (accuracy, RT) plus measures from a computational learning model all suggest that temporal rule learning occurred but did not generalise across modalities, that dynamics of learning (size of TE effect across runs) and explicit knowledge have little to no effect on the strength of TE, and that explicit knowledge affects performance – if at all – in a context dependent manner: only under complex task regimes (unknown target modality) might it partially help to resolve response conflict while it is lowering performance in less complex environments..

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.

092 Effect of the dual orexin receptor antagonist (DORA) daridorexant on behaviour upon awakening in rats and dogs

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A38-A39
Author(s):  
Giorgio Bergamini ◽  
Catherine Roch ◽  
Sean Durkin ◽  
Michel Steiner
Keyword(s):  
Grip Strength ◽  
Motor Skills ◽  
Muscle Weakness ◽  
Motor Behavior ◽  
Motor Impairment ◽  
Phase Behaviour ◽  
Fine Motor ◽  
Dependent Manner ◽  
The Impact ◽  
Time Point

Abstract Introduction The ability to be fast alert and to interact with the environment without motor impairment upon waking up, is a critical feature of natural sleep. DORAs represent a new class of insomnia medications that specifically inhibit the wake-promoting effects of orexin neuropeptides. Daridorexant is a potent and selective DORA under late stage development for the treatment of insomnia. Here, we assessed the impact of sleep-promoting doses of daridorexant on rats’ and dogs’ behaviour upon forced awakening. Zolpidem (a positive GABAA receptor modulator) was used as active comparator in rats because of its known negative impact on motor functions. Methods Rats were woken up at different time points after oral administration of daridorexant (10, 30, 100 mg/kg) or zolpidem (30, 100 mg/kg) during their inactive phase, and repeatedly subjected to two motor tasks: 1) the rotating rod test (lasting 120 sec, at each time point) assessing gross motor skills and coordination, and 2) the forepaw grip strength test assessing fine motor skills and muscle strength. Dogs were presented with food as an external, salient stimulus, three hours after administration of daridorexant in gelatin capsules (10, 30 or 90 mg/dog) during their active phase. Behaviour and signs of muscle weakness, after having woken up, were assessed by manual inspection of video recordings and concomitant electroencephalogram/electromyogram recordings. Results In both the rotarod and grip tests, daridorexant treatment had no effect on motor behavior at any dose or time point tested, while zolpidem significantly reduced the time spent on the rotarod and the grip strength in a dose and time-dependent manner (N=12/group; p<0.001;) (e.g. at 30 min post-dose, time spent on the rotarod was 84, 79–89 and 10–19 sec for vehicle, daridorexant and zolpidem, respectively). Dogs treated with daridorexant were able to wake up easily upon food presentation. They behaved and ate normally and did not show any signs of muscle weakness. Conclusion The type of sleep promoted by daridorexant is surmountable in rats and dogs and similar to physiological sleep. It allows animals to easily wake up, to behave normally without motor impairment and to respond efficiently to the environmental conditions. Support (if any) Funded by Idorsia Pharmaceuticals Ltd

scholarly journals Cross-Reactivity of Rabbit Anti-Bovine Prothrombin/Thrombin IgGs With Bovine Factor V/Va-Related Antigens

2010 ◽  
Vol 16 (5) ◽  
pp. 522-528
Author(s):  
He Zhu ◽  
Debra Hoppensteadt ◽  
Michael Morris ◽  
Jawed Fareed
Keyword(s):  
Western Blotting ◽  
Cross Reactivity ◽  
Time Dependent ◽  
Protein G ◽  
Factor V ◽  
Dependent Manner ◽  
Bovine Thrombin ◽  
Time Points ◽  
Bovine Factor ◽  
Time Point

The purpose of this study was to determine whether rabbit anti-bovine prothrombin/thrombin immunoglobulin Gs (IgGs) would cross-react with bovine factor V/Va-related antigens. Bovine prothrombin, crude thrombin, as well as 2 purified versions of thrombin, that is, thrombin 4A (the previous version of Thrombin-JMI marketed prior to 2008) and 4B (the currently marketed version of Thrombin-JMI), were administrated to individual groups of rabbits on days 0, 21, 42, 91, 123, and 151 using standard immunologic methods. Blood was drawn from each rabbit on days 30, 50, 105, 137, and 165 and the pooled antisera from individual groups were purified to obtain the IgGs using protein G affinity columns. By probing bovine factor V/Va samples, the possible cross-reactivity of each IgG collected at different time points (from day 30 to day 165) was explored using Western blotting techniques. The results indicated that rabbit anti-bovine prothrombin and crude thrombin IgGs could cross-react strongly with bovine factor V/Va in an immunization time-dependent manner. However, antibodies generated in thrombin 4A-treated rabbits presented much weaker cross-reactivity with bovine factor V/Va. Furthermore, no cross-reactivity with bovine factor V/Va-related antigens was observed when the anti-bovine thrombin 4B IgG collected at any time point was used. The results suggest that thrombin 4B preparation contains the least bovine factor V/Va contaminants among the bovine prothrombin/thrombin preparations studied and the amount of bovine factor V/Va contaminants in bovine thrombin 4B is too small to elicit the generation of antibodies against bovine factor V/Va in rabbits.

scholarly journals Curvature sensing steers actin-driven cell migration

2021 ◽  
Author(s):  
Ewa Sitarska ◽  
Silvia Dias Almeida ◽  
Marianne Beckwith ◽  
Julian Stopp ◽  
Yannick Schwab ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Leading Edge ◽  
Membrane Curvature ◽  
Cell Periphery ◽  
Dependent Manner ◽  
Complex Environments ◽  
Time Resolved ◽  
Curvature Sensing ◽  
Membrane Topography

Cell migration is fundamental for the immune response, development, and morphogenesis. For navigation through complex and ever-changing environments, migrating cells require a balance between a stable leading-edge, which is necessary for directional migration, and some unstable features to enable the required dynamic behaviors. The leading edge is often composed of actin-driven protrusions including lamellipodia and ruffles with continuously changing membrane curvature. Whether their membrane topography affects the cell's leading edge and motion persistence in complex environments remains unknown. To study this, we combined a theoretical analysis with machine learning-based segmentation for time-resolved TIRF microscopy, membrane topography analysis from electron microscopy images and microfluidics. We discovered that cell motion persistence and directionality, in both freely moving and environmentally-constrained cells, strongly depend on the curvature-sensing protein Snx33. Specifically, Snx33 promotes leading edge instabilities by locally inhibiting WAVE2- driven actin polymerization in a curvature-dependent manner. Snx33 knockout cells migrate faster and are more persistent during unobstructed migration, but fail when a change in direction is required. Thus, Snx33 is key for steering cell motility in complex environments by facilitating contact inhibition of locomotion and promoting efficient turning. These results identify cell surface topography as an organizing principle at the cell periphery that directs cell migration.

Knowledge Dynamics

2015 ◽  
pp. 103-126
Keyword(s):  
Tacit Knowledge ◽  
Knowledge Creation ◽  
Explicit Knowledge ◽  
Dynamic Theory ◽  
Organizational Knowledge ◽  
Knowledge Conversion ◽  
Seci Model ◽  
Organizational Knowledge Creation ◽  
Knowledge Dynamics ◽  
Cognitive Knowledge

In the chapter about cognitive knowledge, the author introduced the dyad of explicit-tacit knowledge developed by Ikujiro Nonaka and his colleagues. This dyad represents the conceptual framework of the dynamic theory of organizational knowledge creation. The breakthrough of this theory is the SECI model, which consists of four knowledge conversion processes: socialization (from tacit knowledge to tacit knowledge), externalization (from tacit knowledge to explicit knowledge), combination (from explicit knowledge to explicit knowledge), and internalization (from explicit knowledge to tacit knowledge). All of these knowledge conversion processes may happen in Ba, a dynamic context where interactions between people take place. The purpose of this chapter is to present the main concepts and ideas of the dynamic theory of organizational knowledge creation developed by Nonaka and his colleagues, a theory that represents a major contribution to the development of knowledge management.

Long-Term Changes in Excitability Induced by Protein Kinase C Activation in Aplysia Sensory Neurons

1998 ◽  
Vol 79 (3) ◽  
pp. 1210-1218 ◽  
Author(s):  
Frédéric Manseau ◽  
Wayne S. Sossin ◽  
Vincent F. Castellucci
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Sensory Neurons ◽  
Dependent Manner ◽  
Kinase C ◽  
Long Term Changes ◽  
Protein Kinase C Activation ◽  
Time Point

Manseau, Frédéric, Wayne S. Sossin, and Vincent F. Castellucci. Long-term changes in excitability induced by protein kinase C activation in Aplysia sensory neurons. J. Neurophysiol. 79: 1210–1218, 1998. Protein kinases A (PKA) and C (PKC) play a central role as intracellular transducers during simple forms of learning in Aplysia. These two proteins seem to cooperate in mediating the different forms of plasticity underlying behavioral modifications of defensive reflexes in a state- and time-dependent manner. Although short- and long-term changes in the synaptic efficacy of the connections between mechanosensory neurons and motoneurons of the reflex have been well characterized, there is also a distinct intermediate phase of plasticity that is not as well understood. Biochemical and physiological experiments have suggested a role for PKC in the induction and expression of this form of facilitation. In this report, we demonstrate that PKC activation can induce both intermediate- and long-term changes in the excitability of sensory neurons (SNs). Short application of 4β-phorbol ester 12,13-dibutyrate (PDBU), a potent activator of PKC, produced a long-lasting increase in the number of spikes fired by SNs in response to depolarizing current pulses. This effect was observed in isolated cell culture and in the intact ganglion; it was blocked by a selective PKC inhibitor (chelerythrine). Interestingly, the increase in excitability measured at an intermediate-term time point (3 h) after treatment was independent of protein synthesis, while it was disrupted at the long-term (24 h) time point by the general protein synthesis inhibitor, anisomycin. In addition to suggesting that PKC as well as PKA are involved in long-lasting excitability changes, these findings support the idea that memory formation involves multiple stages that are mechanistically distinct at the biochemical level.

scholarly journals Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Mediated Autophagy in Human Granulosa Cells as an Alternative of Programmed Cell Death

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3851-3860 ◽  
Author(s):  
Nicole Duerrschmidt ◽  
Olga Zabirnyk ◽  
Marcin Nowicki ◽  
Albert Ricken ◽  
Fayez A. Hmeidan ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Time Point

The LOX-1 receptor, identified on endothelial cells, mediates the uptake of oxidized low-density lipoprotein (oxLDL). The oxLDL-dependent LOX-1 activation causes endothelial cell apoptosis. We here investigated the presence of LOX-1 in granulosa cells from patients under in vitro fertilization therapy. We were interested in the oxLDL-dependent LOX-1 receptor biology, in particular in the induction of apoptosis. In the human ovary, LOX-1 was localized in regressing antral follicles. In granulosa cell cultures, oxLDL-induced mRNA expression of LOX-1 in a time- and dose-dependent manner. The LOX-1 inhibitors (anti-LOX-1 antibody and κ-carrageenan) abrogated the up-regulation of LOX-1. The oxLDL (100 μg/ml) treatment caused the autophagy form of programmed cell death: 1) reorganization of the actin cytoskeleton at the 6-h time point; 2) uptake of YO-PRO, a marker for the early step of programmed cell death, before propidium iodide staining to signify necrosis; 3) absence of apoptotic bodies and cleaved caspase-3; 4) abundant vacuole formation at the ultrastructural level; and 5) decrease of the autophagosome marker protein MAP LC3-I at the 6-h time point indicative of autophagosome formation. We conclude that follicular atresia is not under the exclusive control of apoptosis. The LOX-1-dependent autophagy represents an alternate form of programmed cell death. Obese women with high blood levels of oxLDL may display an increased rate of autophagic granulosa cell death.

scholarly journals Nicotinamide N-methyltransferase catalyses the N-methylation of the endogenous β-carboline norharman: evidence for a novel detoxification pathway

2016 ◽  
Vol 473 (19) ◽  
pp. 3253-3267 ◽  
Author(s):  
Martin G. Thomas ◽  
Davide Sartini ◽  
Monica Emanuelli ◽  
Matthijs J. van Haren ◽  
Nathaniel I. Martin ◽  
...  
Keyword(s):  
Cell Viability ◽  
Dependent Manner ◽  
Methyltransferase Activity ◽  
Cellular Processes ◽  
Specificity Constant ◽  
Expression Model ◽  
Dose Dependent ◽  
Detoxification Pathway ◽  
Time Point

Nicotinamide N-methyltransferase (NNMT) is responsible for the N-methylation of nicotinamide to 1-methylnicotinamide. Our recent studies have demonstrated that NNMT regulates cellular processes fundamental to the correct functioning and survival of the cell. It has been proposed that NNMT may possess β-carboline (BC) N-methyltransferase activity, endogenously and exogenously produced pyridine-containing compounds which, when N-methylated, are potent inhibitors of Complex I and have been proposed to have a role in the pathogenesis of Parkinson's disease. We have investigated the ability of recombinant NNMT to N-methylate norharman (NH) to 2-N-methylnorharman (MeNH). In addition, we have investigated the toxicity of the BC NH, its precursor 1,2,3,4-tetrahydronorharman (THNH) and its N-methylated metabolite MeNH, using our in vitro SH-SY5Y NNMT expression model. Recombinant NNMT demonstrated NH 2N-methyltransferase activity, with a Km of 90 ± 20 µM, a kcat of 3 × 10−4 ± 2 × 10−5 s−1 and a specificity constant (kcat/Km) of 3 ± 1 s−1 M−1. THNH was the least toxic of all three compounds investigated, whereas NH demonstrated the greatest, with no difference observed in terms of cell viability and cell death between NNMT-expressing and non-expressing cells. In NNMT-expressing cells, MeNH increased cell viability and cellular ATP concentration in a dose-dependent manner after 72 and 120 h incubation, an effect that was not observed after 24 h incubation or in non-NNNT-expressing cells at any time point. Taken together, these results suggest that NNMT may be a detoxification pathway for BCs such as NH.

scholarly journals Dynamic Regulation of the Molecular Mechanisms of Regulatory T Cell Migration in Inflamed Skin

2021 ◽  
Vol 12 ◽  
Author(s):  
M. Ursula Norman ◽  
Zachary Chow ◽  
Sarah L. Snelgrove ◽  
Peemapat Prakongtham ◽  
Michael J. Hickey
Keyword(s):  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Hair Follicles ◽  
Dependent Manner ◽  
Dynamic Regulation ◽  
T Cell Migration ◽  
Phosphoinositide 3 Kinase ◽  
Time Point

The presence of regulatory T cells (Tregs) in skin is important in controlling inflammatory responses in this peripheral tissue. Uninflamed skin contains a population of relatively immotile Tregs often located in clusters around hair follicles. Inflammation induces a significant increase both in the abundance of Tregs within the dermis, and in the proportion of Tregs that are highly migratory. The molecular mechanisms underpinning Treg migration in the dermis are unclear. In this study we used multiphoton intravital microscopy to examine the role of RGD-binding integrins and signalling through phosphoinositide 3-kinase P110δ (PI3K p110δ) in intradermal Treg migration in resting and inflamed skin. We found that inflammation induced Treg migration was dependent on RGD-binding integrins in a context-dependent manner. αv integrin was important for Treg migration 24 hours after induction of inflammation, but contributed to Treg retention at 48 hours, while β1 integrin played a role in Treg retention at the later time point but not during the peak of inflammation. In contrast, inhibition of signalling through PI3K p110δ reduced Treg migration throughout the entire inflammatory response, and also in the absence of inflammation. Together these observations demonstrate that the molecular mechanisms controlling intradermal Treg migration vary markedly according to the phase of the inflammatory response.

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