Traveling Waves in Quasi-One-Dimensional Neuronal Minicolumns

2021 ◽  
pp. 1-26
Author(s):  
Vincent Baker ◽  
Luis Cruz
Keyword(s):  
Traveling Waves ◽  
Propagation Speed ◽  
Biological Properties ◽  
Spike Timing ◽  
Cortical Dynamics ◽  
One Dimensional ◽  
Timing Variability ◽  
Dimensional Network ◽  
Fully Connected

Abstract Traveling waves of neuronal activity in the cortex have been observed in vivo. These traveling waves have been correlated to various features of observed cortical dynamics, including spike timing variability and correlated fluctuations in neuron membrane potential. Although traveling waves are typically studied as either strictly one-dimensional or two-dimensional excitations, here we investigate the conditions for the existence of quasi-one-dimensional traveling waves that could be sustainable in parts of the brain containing cortical minicolumns. For that, we explore a quasi-one-dimensional network of heterogeneous neurons with a biologically influenced computational model of neuron dynamics and connectivity. We find that background stimulus reliably evokes traveling waves in networks with local connectivity between neurons. We also observe traveling waves in fully connected networks when a model for action potential propagation speed is incorporated. The biological properties of the neurons influence the generation and propagation of the traveling waves. Our quasi-one-dimensional model is not only useful for studying the basic properties of traveling waves in neuronal networks; it also provides a simplified representation of possible wave propagation in columnar or minicolumnar networks found in the cortex.

scholarly journals Regular Traveling Waves in a One-Dimensional Network of Theta Neurons

2002 ◽  
Vol 62 (4) ◽  
pp. 1197-1221 ◽  
Author(s):  
Bard Ermentrout ◽  
Jonathan Rubin ◽  
Remus Osan
Keyword(s):  
Traveling Waves ◽  
One Dimensional ◽  
Dimensional Network ◽  
Theta Neurons

Dynamic-Clamp Analysis of the Effects of Convergence on Spike Timing. I. Many Synaptic Inputs

2005 ◽  
Vol 94 (4) ◽  
pp. 2512-2525 ◽  
Author(s):  
Matthew A. Xu-Friedman ◽  
Wade G. Regehr
Keyword(s):  
Spike Timing ◽  
Synaptic Conductance ◽  
Dynamic Clamp ◽  
Synaptic Inputs ◽  
Timing Variability ◽  
Large N ◽  
Auditory Brain Stem ◽  
Sensory Acuity ◽  
Activity Dependent

Precise action potential timing is crucial in sensory acuity and motor control. Convergence of many synaptic inputs is thought to provide a means of decreasing spike-timing variability (“jitter”), but its effectiveness has never been tested in real neurons. We used the dynamic-clamp technique in mouse auditory brain stem slices to examine how convergence controls spike timing. We tested the roles of several synaptic properties that are influenced by ongoing activity in vivo: the number of active inputs ( N), their total synaptic conductance ( Gtot), and their timing, which can resemble an alpha or a Gaussian distribution. Jitter was reduced most with large N, up to a factor of over 20. Variability in N is likely to occur in vivo, but this added little jitter. Jitter reduction also depended on the timing of inputs: alpha-distributed inputs were more effective than Gaussian-distributed inputs. Furthermore, the two distributions differed in their sensitivity to synaptic conductance: for Gaussian-distributed inputs, jitter was most reduced when Gtot was 2–3 times threshold, whereas alpha-distributed inputs showed continued jitter reduction with higher Gtot. However, very high Gtot caused the postsynaptic cell to fire multiple times, particularly when the input jitter outlasted the cell's refractory period, which interfered with jitter reduction. Gtot also greatly affected the response latency, which could influence downstream computations. Changes in Gtot are likely to arise in vivo through activity-dependent changes in synaptic strength. High rates of postsynaptic activity increased the number of synaptic inputs required to evoke a postsynaptic response. Despite this, jitter was still effectively reduced, particularly in cases when this increased threshold eliminated secondary spikes. Thus these studies provide insight into how specific features of converging inputs control spike timing.

scholarly journals The Impact of Spike Timing Variability on the Signal-Encoding Performance of Neural Spiking Models

2002 ◽  
Vol 14 (2) ◽  
pp. 347-367 ◽  
Author(s):  
Amit Manwani ◽  
Peter N. Steinmetz ◽  
Christof Koch
Keyword(s):  
Channel Model ◽  
Spike Trains ◽  
Spike Timing ◽  
Noise Sources ◽  
Timing Variability ◽  
Optimal Linear ◽  
Signal Encoding ◽  
Neuronal Spike Trains ◽  
The Impact

It remains unclear whether the variability of neuronal spike trains in vivo arises due to biological noise sources or represents highly precise encoding of temporally varying synaptic input signals. Determining the variability of spike timing can provide fundamental insights into the nature of strategies used in the brain to represent and transmit information in the form of discrete spike trains. In this study, we employ a signal estimation paradigm to determine how variability in spike timing affects encoding of random time-varying signals. We assess this for two types of spiking models: an integrate-and-fire model with random threshold and a more biophysically realistic stochastic ion channel model. Using the coding fraction and mutual information as information-theoretic measures, we quantify the efficacy of optimal linear decoding of random inputs from the model outputs and study the relationship between efficacy and variability in the output spike train. Our findings suggest that variability does not necessarily hinder signal decoding for the biophysically plausible encoders examined and that the functional role of spiking variability depends intimately on the nature of the encoder and the signal processing task; variability can either enhance or impede decoding performance.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

2019 ◽  
Vol 20 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Abdullah M. Alnuqaydan ◽  
Bilal Rah
Keyword(s):  
Medicinal Plant ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biological Properties ◽  
In Vivo Model ◽  
Drug Candidate ◽  
Phytochemical Analysis ◽  
Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

Neuropharmacological Screening of Chiral and Non-chiral Phthalimide- Containing Compounds in Mice: in vivo and in silico Experiments

2019 ◽  
Vol 15 (1) ◽  
pp. 102-118 ◽  
Author(s):  
Carolina Campos-Rodríguez ◽  
José G. Trujillo-Ferrara ◽  
Ameyali Alvarez-Guerra ◽  
Irán M. Cumbres Vargas ◽  
Roberto I. Cuevas-Hernández ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
In Silico ◽  
Biological Properties ◽  
Chiral Molecules ◽  
Chiral Compounds ◽  
Plus Maze ◽  
In Silico Studies ◽  
The Central Nervous System

Background: Thalidomide, the first synthesized phthalimide, has demonstrated sedative- hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. Objective: Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested. Method: Homology modeling and molecular docking were employed to predict recognition of the analogues by hNMDA and mGlu receptors. The neuropharmacological activity was tested with the open field test and elevated plus maze (EPM). The compounds were tested in mouse models of acute convulsions induced either by pentylenetetrazol (PTZ; 90 mg/kg) or 4-aminopyridine (4-AP; 10 mg/kg). Results: The ortho and para non-chiral compounds at 562.3 and 316 mg/kg, respectively, decreased locomotor activity. Contrarily, the chiral compounds produced excitatory effects. Increased locomotor activity was found with S-TGLU and R-TGLU at 100, 316 and 562.3 mg/kg, and S-TASP at 316 and 562.3 mg/kg. These molecules showed no activity in the EPM test or PTZ model. In the 4-AP model, however, S-TGLU (237.1, 316 and 421.7 mg/kg) as well as S-TASP and R-TASP (316 mg/kg) lowered the convulsive and death rate. Conclusion: The chiral compounds exhibited a non-competitive NMDAR antagonist profile and the non-chiral molecules possessed selective sedative properties. The NMDAR exhibited stereoselectivity for S-TGLU while it is not a preference for the aspartic derivatives. The results appear to be supported by the in silico studies, which evidenced a high affinity of phthalimides for the hNMDAR and mGluR type 1.

Development and Pharmacokinetics Study of Antifungal Peptide Nanoliposomes by Liquid Chromatography-tandem Mass Spectrometry

2019 ◽  
Vol 15 (4) ◽  
pp. 312-318
Author(s):  
Shuoye Yang
Keyword(s):  
Mass Spectrometry ◽  
Biological Properties ◽  
Pharmacokinetic Property ◽  
Antifungal Peptide ◽  
Simple Liquid ◽  
Physico Chemical ◽  
Liquid Chromatography Tandem Mass ◽  
Pegylated Lipids

Background: The therapeutic ability and application of antifungal peptide (APs) are limited by their physico-chemical and biological properties, the nano-liposomal encapsulation would improve the in vivo circulation and stability. </P><P> Objective: To develop a long-circulating liposomal delivery systems encapsulated APs-CGA-N12 with PEGylated lipids and cholesterol, and investigated through in vivo pharmacokinetics. Methods: The liposomes were prepared and characterized, a rapid and simple liquid chromatographytandem mass spectrometry (LC-MS/MS) assay was developed for the determination of antifungal peptide in vivo, the pharmacokinetic characteristics of APs liposomes were evaluated in rats. Results: Liposomes had a large, unilamellar structure, particle size and Zeta potential ranged from 160 to 185 nm and -0.55 to 1.1 mV, respectively. The results indicated that the plasma concentration of peptides in reference solutions rapidly declined after intravenous administration, whereas the liposomeencapsulated ones showed slower elimination. The AUC(0-∞) was increased by 3.0-fold in liposomes in comparison with standard solution (20 mg·kg-1), the half-life (T1/2) was 1.6- and 1.5-fold higher compared to the reference groups of 20 and 40 mg·kg-1, respectively. Conclusion: Therefore, it could be concluded that liposomal encapsulation effectively improved the bioavailability and pharmacokinetic property of antifungal peptides.

Development of Mucoadhesive Buccal Drug Delivery System of Propranolol Hydrochloride Using Aster ericoides Mucilage

2020 ◽  
Vol 10 (2) ◽  
pp. 133-148
Author(s):  
Ankaj Kaundal ◽  
Pravin Kumar ◽  
Rajendra Awasthi ◽  
Giriraj T. Kulkarni
Keyword(s):  
Buccal Cavity ◽  
Three Dimensional ◽  
Hot Water ◽  
Fickian Diffusion ◽  
Aster Ericoides ◽  
Dimensional Network ◽  
Buccal Tablet ◽  
Significant Difference ◽  
Volunteer Group

Aim: The study was aimed to develop mucoadhesive buccal tablets using Aster ericoides leaves mucilage. Background : Mucilages are naturally occurring high-molecular-weight polyuronides, which have been extensively studied for their application in different pharmaceutical dosage forms. Objective: The objective of the present research was to establish the mucilage isolated from the leaves of Aster ericoides as an excipient for the formulation of the mucoadhesive buccal tablet. Method: The mucilage was isolated from the leaves of Aster ericoides by maceration, precipitated with acetone and characterized. Tablets were prepared using wet granulation technique and evaluated for various official tests. Results: The mucilage was found to be non-toxic on A-431 and Vero cell lines. It was insoluble but swellable in cold and hot water. The results indicate that mucilage can form a three-dimensional network. The pH of the mucilage (6.82 ± 0.13) indicated that it might be non-irritant to the buccal cavity. The mucilage was found to be free from microbes. The release of drug was by Fickian diffusion. The in vivo buccal tablet acceptance was 80%. No significant difference between the diastolic blood pressure of standard and Aster tablets treated volunteer group was recorded. Conclusion: The mucilage was found to be non-toxic on A-431 and Vero cell lines. It was insoluble but swellable in cold and hot water. The results indicate that mucilage can form a three-dimensional network. The pH of the mucilage (6.82 ± 0.13) indicated that it might be non-irritant to the buccal cavity. The mucilage was found to be free from microbes. The release of drug was by Fickian diffusion. The in vivo buccal tablet acceptance was 80%. No significant difference between the diastolic blood pressure of standard and Aster tablets treated volunteer group was recorded. Other: However, to prove the potency of the polymer, in vivo bioavailability studies in human volunteers are needed along with chronic toxicity studies in suitable animal models.

scholarly journals 99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 128 ◽  
Author(s):  
Giglio ◽  
Rey
Keyword(s):  
Rational Design ◽  
Biological Properties ◽  
Fine Tuning ◽  
Oxidation States ◽  
Hypoxia Imaging ◽  
Biological Target ◽  
99Mtc Radiopharmaceuticals ◽  
99Mtc Labelling

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [18F]Fluoromisonidazole (FMISO) is also presented.

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