scholarly journals Neurocomputational modeling of the basal ganglia in motor learning at mesoscopic scale: an overview

2021 ◽  
Author(s):  
Ilaria Gigi ◽  
Rosa Senatore ◽  
Angelo Marcelli
Keyword(s):  
Basal Ganglia ◽  
Motor Learning ◽  
Computational Models ◽  
Physiological Model ◽  
Neural Systems ◽  
Multimodal Analysis ◽  
In Vivo Experiments ◽  
Research Advance ◽  
Scientific Results

The first model of the basal ganglia (BG) was conceived almost half a century ago. Since then, extensive research efforts have been carried out to further refine and understand the physiological and pathological BG behaviour and role. Currently, it is well-known that the BG are crucial in motor learning and motor diseases are associated to dysfunction of the nuclei, such as the parkinsonian syndrome, dystonia, chorea, etc. We are still a long way from giving an answer to all the questions, but advances in technology are making research advance significantly in recent years. Computational modeling is one of these methodologies and allows to evaluate the interactions within and among multiple neural systems. The development and analysis of the behaviour of computational models, in concert with multimodal analysis and in vivo experiments, leads to new scientific results. This review provides a critical synopsis of the evolution of thought regarding the physiological model of the BG with respect to motor learning, revisiting past theories and summarizing the main recent findings to this field of research, to highlight their innovative contribution to knowledge of the functioning of the nuclei and formulate a state-of-art hypothesis of BG modeling.

scholarly journals Reconfiguration of the Pontomedullary Respiratory Network: A Computational Modeling Study With Coordinated In Vivo Experiments

2008 ◽  
Vol 100 (4) ◽  
pp. 1770-1799 ◽  
Author(s):  
I. A. Rybak ◽  
R. O'Connor ◽  
A. Ross ◽  
N. A. Shevtsova ◽  
S. C. Nuding ◽  
...  
Keyword(s):  
Computational Models ◽  
Ad Hoc ◽  
Large Body ◽  
Network Activity ◽  
Respiratory Pattern ◽  
Respiratory Neurons ◽  
Phase Switching ◽  
In Vivo Experiments ◽  
Respiratory Network

A large body of data suggests that the pontine respiratory group (PRG) is involved in respiratory phase-switching and the reconfiguration of the brain stem respiratory network. However, connectivity between the PRG and ventral respiratory column (VRC) in computational models has been largely ad hoc. We developed a network model with PRG-VRC connectivity inferred from coordinated in vivo experiments. Neurons were modeled in the “integrate-and-fire” style; some neurons had pacemaker properties derived from the model of Breen et al. We recapitulated earlier modeling results, including reproduction of activity profiles of different respiratory neurons and motor outputs, and their changes under different conditions (vagotomy, pontine lesions, etc.). The model also reproduced characteristic changes in neuronal and motor patterns observed in vivo during fictive cough and during hypoxia in non-rapid eye movement sleep. Our simulations suggested possible mechanisms for respiratory pattern reorganization during these behaviors. The model predicted that network- and pacemaker-generated rhythms could be co-expressed during the transition from gasping to eupnea, producing a combined “burst-ramp” pattern of phrenic discharges. To test this prediction, phrenic activity and multiple single neuron spike trains were monitored in vagotomized, decerebrate, immobilized, thoracotomized, and artificially ventilated cats during hypoxia and recovery. In most experiments, phrenic discharge patterns during recovery from hypoxia were similar to those predicted by the model. We conclude that under certain conditions, e.g., during recovery from severe brain hypoxia, components of a distributed network activity present during eupnea can be co-expressed with gasp patterns generated by a distinct, functionally “simplified” mechanism.

Modelling the Dynamics of Cow-Calf Dyadic Behavior

2018 ◽  
Vol 7 (4) ◽  
pp. 1-19
Author(s):  
Luciandra Macedo de Toledo ◽  
Thayná Barcelos Fernandes ◽  
Mateus José Rodrigues Paranhos da Costa ◽  
Luis Alberto Ambrósio
Keyword(s):  
Animal Behavior ◽  
Computational Models ◽  
Ecological Factors ◽  
In Vivo Experiments ◽  
Behavioral System ◽  
Cow Calf ◽  
Reducing Costs ◽  
Experimental Use ◽  
Dynamics Method

The dynamics of the first suckling is critical for the formation of the complex cow-calf dyad system, where interactions occur among animals and natural and anthropic environments. In this study, the system dynamics method was applied to build conceptual and computational models to better understand the dynamics of dyadic behavior and its interactions with the environment. The model showed that dyadic behavior is manifested by reinforcing feedback loops in which the calf stimulates the cow's maternal functions, which in turn results in caring stimuli towards the calf. Moreover, ecological factors affect the performance of the animals' behavioral system by influencing the rate of direct events for both, cow and calf. The cow-calf dyad model can be used in silico experiments involving animal behavior, which allows computational verification of dynamic ex-ante hypotheses in vivo experiments, thus reducing costs and honoring the ethical principle of minimizing the experimental use of animals.

scholarly journals Erythrocytes: Oxygen Sensors and Modulators of Vascular Tone

Physiology ◽  
2009 ◽  
Vol 24 (2) ◽  
pp. 107-116 ◽  
Author(s):  
Mary L. Ellsworth ◽  
Christopher G. Ellis ◽  
Daniel Goldman ◽  
Alan H. Stephenson ◽  
Hans H. Dietrich ◽  
...  
Keyword(s):  
Vascular Tone ◽  
Computational Models ◽  
Control Mechanism ◽  
Atp Release ◽  
Oxygen Demand ◽  
Oxygen Sensors ◽  
Feedback Mechanisms ◽  
In Vivo Experiments ◽  
The Impact

Through oxygen-dependent release of the vasodilator ATP, the mobile erythrocyte plays a fundamental role in matching microvascular oxygen supply with local tissue oxygen demand. Signal transduction within the erythrocyte and microvessels as well as feedback mechanisms controlling ATP release have been described. Our understanding of the impact of this novel control mechanism will rely on the integration of in vivo experiments and computational models.

Recent Advances and Challenges of the Drugs Acting on Monoamine Transporters

2020 ◽  
Vol 27 (23) ◽  
pp. 3830-3876 ◽  
Author(s):  
Weiwei Xue ◽  
Tingting Fu ◽  
Guoxun Zheng ◽  
Gao Tu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Computational Models ◽  
Binding Mode ◽  
Monoamine Transporters ◽  
Ligand Interaction ◽  
Structure Based Drug Design ◽  
Design And Synthesis ◽  
In Vivo Experiments ◽  
Approved Drugs

Background: The human Monoamine Transporters (hMATs), primarily including hSERT, hNET and hDAT, are important targets for the treatment of depression and other behavioral disorders with more than the availability of 30 approved drugs. Objective: This paper is to review the recent progress in the binding mode and inhibitory mechanism of hMATs inhibitors with the central or allosteric binding sites, for the benefit of future hMATs inhibitor design and discovery. The Structure-Activity Relationship (SAR) and the selectivity for hit/lead compounds to hMATs that are evaluated by in vitro and in vivo experiments will be highlighted. Methods: PubMed and Web of Science databases were searched for protein-ligand interaction, novel inhibitors design and synthesis studies related to hMATs. Results: Literature data indicate that since the first crystal structure determinations of the homologous bacterial Leucine Transporter (LeuT) complexed with clomipramine, a sizable database of over 100 experimental structures or computational models has been accumulated that now defines a substantial degree of structural variability hMATs-ligands recognition. In the meanwhile, a number of novel hMATs inhibitors have been discovered by medicinal chemistry with significant help from computational models. Conclusion: The reported new compounds act on hMATs as well as the structures of the transporters complexed with diverse ligands by either experiment or computational modeling have shed light on the poly-pharmacology, multimodal and allosteric regulation of the drugs to transporters. All of the studies will greatly promote the Structure-Based Drug Design (SBDD) of structurally novel scaffolds with high activity and selectivity for hMATs.

scholarly journals Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Edgar Peña ◽  
Nicole A. Pelot ◽  
Warren M. Grill
Keyword(s):  
Direct Current ◽  
Computational Models ◽  
Nerve Fibers ◽  
In Vivo Studies ◽  
Signal Frequency ◽  
Frequency Dependent ◽  
Charge Imbalance ◽  
In Vivo Experiments ◽  
Current Block

AbstractReversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.

scholarly journals Microstructural organizational patterns in the human corticostriatal system

2012 ◽  
Vol 107 (11) ◽  
pp. 2984-2995 ◽  
Author(s):  
Timothy D. Verstynen ◽  
David Badre ◽  
Kevin Jarbo ◽  
Walter Schneider
Keyword(s):  
Basal Ganglia ◽  
Computational Models ◽  
Ex Vivo ◽  
Local Level ◽  
Fiber Tractography ◽  
Asymmetry Of Information ◽  
Cortical Areas ◽  
Posterior Direction ◽  
Organizational Patterns

The axons that project into the striatum are known to segregate according to macroscopic cortical systems; however, the within-region organization of these fibers has yet to be described in humans. We used in vivo fiber tractography, in neurologically healthy adults, to map white matter bundles that originate in different neocortical areas, navigate complex fiber crossings, and project into the striatum. As expected, these fibers were generally segregated according to cortical origin. Within a subset of pathways, a patched pattern of inputs was observed, consistent with previous ex vivo histological studies. In projections from the prefrontal cortex, we detected a topography in which fibers from rostral prefrontal areas projected mostly to rostral parts of the striatum and vice versa for inputs originating in caudal cortical areas. Importantly, within this prefrontal system there was also an asymmetry in the subset of divergent projections, with more fibers projecting in a posterior direction than anterior. This asymmetry of information projecting into the basal ganglia was predicted by previous network-level computational models. A rostral-caudal topography was also present at the local level in otherwise somatotopically organized fibers projecting from the motor cortex. This provides clear evidence that the longitudinal organization of input fields, observed at the macroscopic level across cortical systems, is also found at the microstructural scale at which information is segregated as it enters the human basal ganglia.

Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

2020 ◽  
Author(s):  
Prithiv K R Kumar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Tissue Remodelling ◽  
Major Health Problem ◽  
In Vivo Experiments ◽  
Renal Regeneration ◽  
Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

In vivo Experiments of Natural Products Protection of Antagonistic Effects of Lead on Iron

2018 ◽  
Vol 68 (12) ◽  
pp. 2747-2751
Author(s):  
Marioara Nicula ◽  
Nicolae Pacala ◽  
Lavinia Stef ◽  
Ioan Pet ◽  
Dorel Dronca ◽  
...  
Keyword(s):  
Aquatic Environment ◽  
Iron Homeostasis ◽  
Iron Concentration ◽  
Antagonistic Effect ◽  
Tissue Samples ◽  
Antagonistic Effects ◽  
In Vivo Experiments ◽  
Living Organisms ◽  
Toxic Potential

Living organisms take nutrients from the environment, and together with them, substances with toxic potential � such as heavy metals. Lead is one common metal pollutant especially in aquatic environment, from where the fish can be intoxicated very easily. Bioavailability, distribution, toxic action, synergistic and antagonistic effects are characteristics which can alter the fish health. Our experimental study followed the effects of lead overload in water on iron distribution, in different tissues sample Carassius gibelio Bloch fish. We performed the experiment in four different fish groups: control C; lead � Pb (administration of lead in water 0.075mg/mL of water, as Pb(NO3)2 x � H2O); lead (the same dose) and 2% of freeze-dry garlic incorporated into fishes� food � Pb+garlic; lead (the same dose) and 2% chlorella incorporated into fishes� food � Pb+chlorella, for 21 consecutive days. The iron concentration was analysed with AAS (Atomic Absorption Spectroscopy) from gills, muscle, skin (and scales), intestine, liver, heart, brain, ovary, testicles, and kidney. The obtained data presented a significantly decrease of iron content in all tested tissue samples that demonstrated, alteration of iron homeostasis, explained by a strong antagonistic effect of lead on iron. Our experiment showed that biologic active principles from garlic and chlorella act like natural protectors, and potentiate the iron deficiency even in the case of lead overload in aquatic environment, for fish.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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