scholarly journals Computational study of synchrony in fields and microclusters of ephaptically coupled neurons

2015 ◽  
Vol 113 (9) ◽  
pp. 3229-3241 ◽  
Author(s):  
R. Greg Stacey ◽  
Lennart Hilbert ◽  
Thomas Quail
Keyword(s):  
Electric Fields ◽  
Computational Study ◽  
Extracellular Volume ◽  
Low Frequency ◽  
Spike Timing ◽  
Single Action ◽  
Neuronal Synchrony ◽  
Single Spike ◽  
Ephaptic Coupling

Neuronal hypersynchrony is implicated in epilepsy and other diseases. The low-frequency, spatially averaged electric fields from many thousands of neurons have been shown to promote synchrony. It remains unclear whether highly transient, spatially localized electric fields from single action potentials (ephaptic coupling) significantly affect spike timing of neighboring cells and in consequence, population synchrony. In this study, we simulated the extracellular potentials and the resulting coupling between neurons in the NEURON environment and generalized their connection rules to create an oscillator network model of a sheet of ephaptically coupled neurons. With the use of both models, we explained several aspects of epileptiform behavior not previously modeled by synaptically coupled networks. Importantly, reduction of neuron spacing induced synchronization via single-spike ephaptic coupling, agreeing with seizure suppression seen clinically and in vitro via extracellular volume adjustment. Further reduction of neuron spacing yielded locally synchronized clusters, providing a mechanism for recent in vitro observations of localized neuronal synchrony in the absence of synaptic and gap-junction coupling.

scholarly journals Short-term dosage regimen for stimulation-induced long-lasting desynchronization

2017 ◽  
Author(s):  
Thanos Manos ◽  
Magteld Zeitler ◽  
Peter A. Tass
Keyword(s):  
Dosage Regimen ◽  
Computational Study ◽  
Spike Timing ◽  
Stimulation Frequency ◽  
Dose Finding ◽  
Short Term ◽  
Neuronal Synchrony ◽  
Stimulation Parameters ◽  
Human Dose ◽  
Parameter Values

AbstractIn this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e. an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g. if the CR stimulation frequency (i.e. stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long-term desynchronization at comparably short stimulation duration and low integral stimulation duration. Currently, clinical proof of concept is available for deep brain CR stimulation for Parkinson’s therapy and acoustic CR stimulation for tinnitus therapy. Promising first in human data is available for vibrotactile CR stimulation for Parkinson’s treatment. For the clinical development of these treatments it is mandatory to perform dose-finding studies to reveal optimal stimulation parameters and dosage regimens. Our findings can straightforwardly be tested in human dose-finding studies.

scholarly journals An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials

2018 ◽  
Vol 30 (5) ◽  
pp. 1296-1322 ◽  
Author(s):  
Reinoud Maex
Keyword(s):  
Computational Study ◽  
Electrical Coupling ◽  
Field Potential ◽  
Low Frequency ◽  
Reciprocal Inhibition ◽  
Mammalian Brain ◽  
Power Scaling ◽  
Field Potentials ◽  
Neuronal Synchrony ◽  
Α Rhythm

Recent advances in engineering and signal processing have renewed the interest in invasive and surface brain recordings, yet many features of cortical field potentials remain incompletely understood. In the computational study that follows, we show that a model circuit of interneurons, coupled via both GABAA receptor synapses and electrical synapses, reproduces many essential features of the power spectrum of local field potential (LFP) recordings, such as 1/ f power scaling at low frequency (below 10 Hz), power accumulation in the γ-frequency band (30–100 Hz), and a robust α rhythm in the absence of stimulation. The low-frequency 1/ f power scaling depends on strong reciprocal inhibition, whereas the α rhythm is generated by electrical coupling of intrinsically active neurons. As in previous studies, the γ power arises through the amplification of single-neuron spectral properties, owing to the refractory period, by parameters that favor neuronal synchrony, such as delayed inhibition. This study also confirms that both synaptic and voltage-gated membrane currents contribute substantially to the LFP and that high-frequency signals such as action potentials quickly taper off with distance. Given the ubiquity of electrically coupled interneuron circuits in the mammalian brain, they may be major determinants of the recorded potentials.

scholarly journals Modulation of Cellular Response to Different Parameters of the Rotating Magnetic Field (RMF)—An In Vitro Wound Healing Study

2021 ◽  
Vol 22 (11) ◽  
pp. 5785
Author(s):  
Magdalena Jedrzejczak-Silicka ◽  
Marian Kordas ◽  
Maciej Konopacki ◽  
Rafał Rakoczy
Keyword(s):  
Magnetic Field ◽  
Wound Healing ◽  
Magnetic Fields ◽  
Electric Fields ◽  
Metabolic Activity ◽  
Cellular Response ◽  
Healing Process ◽  
Low Frequency ◽  
Rotating Magnetic Field

Since the effect of MFs (magnetic fields) on various biological systems has been studied, different results have been obtained from an insignificant effect of weak MFs on the disruption of the circadian clock system. On the other hand, magnetic fields, electromagnetic fields, or electric fields are used in medicine. The presented study was conducted to determine whether a low-frequency RMF (rotating magnetic field) with different field parameters could evoke the cellular response in vitro and is possible to modulate the cellular response. The cellular metabolic activity, ROS and Ca2+ concentration levels, wound healing assay, and gene expression analyses were conducted to evaluate the effect of RMF. It was shown that different values of magnetic induction (B) and frequency (f) of RMF evoke a different response of cells, e.g., increase in the general metabolic activity may be associated with the increasing of ROS levels. The lower intracellular Ca2+ concentration (for 50 Hz) evoked the inability of cells to wound closure. It can be stated that the subtle balance in the ROS level is crucial in the wound for the effective healing process, and it is possible to modulate the cellular response to the RMF in the context of an in vitro wound healing.

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

Domain dynamics of strontium-barium niobate crystals in low-frequency electric fields

1990 ◽  
Vol 111 (1) ◽  
pp. 299-305 ◽  
Author(s):  
A. I. Bezhanova ◽  
V. I. Silvestrov ◽  
T. A. Zeinalova ◽  
T. R. Volk
Keyword(s):  
Electric Fields ◽  
Low Frequency ◽  
Strontium Barium Niobate ◽  
Strontium Barium ◽  
Domain Dynamics

scholarly journals Establishment of a New Device for Electrical Stimulation of Non-Degenerative Cartilage Cells In Vitro

2021 ◽  
Vol 22 (1) ◽  
pp. 394
Author(s):  
Simone Krueger ◽  
Alexander Riess ◽  
Anika Jonitz-Heincke ◽  
Alina Weizel ◽  
Anika Seyfarth ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Electric Fields ◽  
Cartilage Tissue ◽  
Type I ◽  
Dependent Manner ◽  
New Device ◽  
Alternating Electric Fields ◽  
Cartilage Cells ◽  
Stimulation Of

In cell-based therapies for cartilage lesions, the main problem is still the formation of fibrous cartilage, caused by underlying de-differentiation processes ex vivo. Biophysical stimulation is a promising approach to optimize cell-based procedures and to adapt them more closely to physiological conditions. The occurrence of mechano-electrical transduction phenomena within cartilage tissue is physiological and based on streaming and diffusion potentials. The application of exogenous electric fields can be used to mimic endogenous fields and, thus, support the differentiation of chondrocytes in vitro. For this purpose, we have developed a new device for electrical stimulation of chondrocytes, which operates on the basis of capacitive coupling of alternating electric fields. The reusable and sterilizable stimulation device allows the simultaneous use of 12 cavities with independently applicable fields using only one main supply. The first parameter settings for the stimulation of human non-degenerative chondrocytes, seeded on collagen type I elastin-based scaffolds, were derived from numerical electric field simulations. Our first results suggest that applied alternating electric fields induce chondrogenic re-differentiation at the gene and especially at the protein level of human de-differentiated chondrocytes in a frequency-dependent manner. In future studies, further parameter optimizations will be performed to improve the differentiation capacity of human cartilage cells.

Computational study for suppression of CD25/IL-2 interaction

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Moein Dehbashi ◽  
Zohreh Hojati ◽  
Majid Motovali-bashi ◽  
Mazdak Ganjalikhani-Hakemi ◽  
Akihiro Shimosaka ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cancer Progression ◽  
Immune Escape ◽  
De Novo ◽  
Computational Study ◽  
Treg Cells ◽  
Homology Search ◽  
Small Interfering Rnas

AbstractCancer recurrence presents a huge challenge in cancer patient management. Immune escape is a key mechanism of cancer progression and metastatic dissemination. CD25 is expressed in regulatory T (Treg) cells including tumor-infiltrating Treg cells (TI-Tregs). These cells specially activate and reinforce immune escape mechanism of cancers. The suppression of CD25/IL-2 interaction would be useful against Treg cells activation and ultimately immune escape of cancer. Here, software, web servers and databases were used, at which in silico designed small interfering RNAs (siRNAs), de novo designed peptides and virtual screened small molecules against CD25 were introduced for the prospect of eliminating cancer immune escape and obtaining successful treatment. We obtained siRNAs with low off-target effects. Further, small molecules based on the binding homology search in ligand and receptor similarity were introduced. Finally, the critical amino acids on CD25 were targeted by a de novo designed peptide with disulfide bond. Hence we introduced computational-based antagonists to lay a foundation for further in vitro and in vivo studies.

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