scholarly journals Crustacean cardiac ganglion model reveals constraints on morphology and conductances

2021 ◽  
Author(s):  
Daniel S Dopp ◽  
Pranit S Samarth ◽  
Jing S Wang ◽  
Daniel R Kick ◽  
David J Schulz ◽  
...  
Keyword(s):  
Single Cell ◽  
Large Cell ◽  
Biophysical Model ◽  
Cardiac Ganglion ◽  
Initiation Zone ◽  
Unknown Structure ◽  
Network Coordinates ◽  
Large Motor ◽  
Motor Cells ◽  
Spike Initiation

The crustacean cardiac ganglion (CG) network coordinates the rhythmic contractions of the heart muscle to control the circulation of blood. The network consists of 9 cells, 5 large motor cells (LC1-5) and 4 small endogenous pacemaker cells (SCs). We report a new three-compartmental biophysical model of an LC that is morphologically realistic and includes provision for inputs from the SCs via a gap-junction coupled spike-initiation-zone (SIZ) compartments. To determine physiologically viable LC models in this realistic configuration, maximal conductances in three compartments of an LC are determined by random sampling from a biologically-characterized 9D-parameter space, followed by a three stage rejection protocol that checks for conformity with electrophysiological features from single cell traces. LC models that pass the single cell rejection protocol are then incorporated into a network model which is then used in a final rejection protocol stage. Using disparate experimental data, the study provides hitherto unknown structure-function insights related to the crustacean cardiac ganglion large cell, including predictions about morphology including the role of its SIZ, and the differential roles of active conductances in the three compartments. Further, we extend analyses of emergent conductance relationships and correlations in model neurons relative to their biological counterparts, allowing us to make inferences both with respect to the biological system as well as the implications of the ability to detect such relationships in populations of model neurons going forward.

Impulse Identification and Axon Mapping of the Nine Neurons in the Cardiac Ganglion of the Lobster Homarus Americanus

1967 ◽  
Vol 47 (2) ◽  
pp. 327-341
Author(s):  
DANIEL K. HARTLINE
Keyword(s):  
Large Cell ◽  
Homarus Americanus ◽  
Simultaneous Recording ◽  
Small Cell ◽  
Complete Analysis ◽  
Cardiac Ganglion ◽  
Cell Identification ◽  
Cell Axon ◽  
Synaptic Interactions ◽  
Stimulation Of

1. Simultaneous recording from several pairs of electrodes placed along the ganglion and certain efferent nerves, during stimulation of other efferents, allows the course of antidromic impulses in each stimulated axon to be mapped. 2. These impulses disappear as they approach their somata, being incapable of invading them, a fact which permits identification of a particular efferent axon with a particular soma. 3. By these means the courses of all such efferent axons, and their corresponding somata, have been determined. These all belong to the five large cells. 4. The impulses from each such axon occurring during the spontaneous burst can be identified, as can impulses from each small cell. 5. Each large-cell axon appears to be inexcitable until it is a few mm from the soma. 6. If the axon branches within this inexcitable region, the branches tend to fire impulses independently. 7. The technique of cell identification opens the way to a more complete analysis of the ganglion's activity and the synaptic interactions which produce it.

scholarly journals The cytomorphologic spectrum of small-cell carcinoma and large-cell neuroendocrine carcinoma in body cavity effusions: A study of 68 cases

CytoJournal ◽  
2011 ◽  
Vol 8 ◽  
pp. 18 ◽  
Author(s):  
Walid E. Khalbuss ◽  
Huaitao Yang ◽  
Qian Lian ◽  
Abdelmonem Elhosseiny ◽  
Liron Pantanowitz ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Single Cell ◽  
Small Cell Carcinoma ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Body Cavity ◽  
Small Cell ◽  
Cell Clusters ◽  
Cell Pattern ◽  
Ancillary Studies

Background: Small-cell carcinoma (SCC) and large-cell neuroendocrine carcinoma (LCNEC) are uncommon in serous body cavity effusions. The purpose of this study is to examine the cytomorphological spectrum of SCC and LCNEC in body cavity serous fluids. Materials and Methods: We have 68 cases from 53 patients who had metastatic SCC or LCNEC diagnoses. All cytology slides and the available clinical data, histological follow-up, and ancillary studies were reviewed. Results: A total of 68 cases (60 pleural, 5 peritoneal, and 3 pericardial effusions) from 53 patients with an average age of 73 years (age range 43-92 years) were reported as diagnostic or suspicious of SCC (52 cases) or LCNEC (16 cases). The primary site was lung in 56 cases, pancreas in 6 cases, and 2 cases each from cervix, colon, and the head and neck region. Of the 68 cases, 48 cases had no history of malignancy of the same type. Ancillary studies were used in 46 cases (68%) including flow cytometric studies in 5 cases. There were three predominant cytomorphological patterns observed including small-cell clusters with prominent nuclear molding (33 cases, 49%), large-cell clusters mimicking non-small-cell carcinoma (18 cases, 26%), and single-cell pattern mimicking lymphoma (17 cases, 25%). Significant apoptosis was seen in 22 cases (33%) and marked tumor cell cannibalism was seen in 11 cases (16%). Nucleoli were prominent in 16 cases (24%). The most frequent neuroendocrine markers performed were synaptophysin and chromogranin. Conclusions: The most common cytomorphologic patterns seen in body cavity effusions of SCC and LCNEC were small-cell clusters with nuclear molding. However, in 51% of the cases either a predominant single-cell pattern mimicking lymphoma or large-cell clusters mimicking non-small carcinoma were noted. In our experience, effusions were the first manifestation of disease in the majority of patients diagnosed with neuroendocrine carcinoma. Therefore, familiarity with the cytomorphological spectrum of neuroendocrine carcinomas in fluid cytology may help in rapidly establishing an accurate diagnosis and in directing appropriate management.

scholarly journals Location and Plasticity of the Sodium Spike Initiation Zone in Nociceptive Terminals In Vivo

Neuron ◽  
2019 ◽  
Vol 102 (4) ◽  
pp. 801-812.e5 ◽  
Author(s):  
Robert H. Goldstein ◽  
Omer Barkai ◽  
Almudena Íñigo-Portugués ◽  
Ben Katz ◽  
Shaya Lev ◽  
...  
Keyword(s):  
Initiation Zone ◽  
Spike Initiation

scholarly journals Resolution of DNA damage at the single-cell level shows largely different actions of X-rays and bleomycin.

1995 ◽  
Vol 43 (2) ◽  
pp. 229-235 ◽  
Author(s):  
M I Affentranger ◽  
W Burkart
Keyword(s):  
Single Cell ◽  
Cell Population ◽  
Large Cell ◽  
Dna Strand Breaks ◽  
Single Cell Level ◽  
X Rays ◽  
Cell Level ◽  
Strand Breaks ◽  
Two Agents ◽  
Dna Strand

Both X-rays and the radiomimetic agent bleomycin (BLM) induce DNA strand breaks, predominantly via reactive radicals. To compare the induction of breaks with the two agents in Chinese hamster (CHO-K1) cells, two different alkaline unwinding methods, a 3H tracer-based analysis of large cell populations and an optical adaption allowing measurement of single cells, were applied. Radiation and BLM show qualitatively similar dose responses when the average number of DNA strand breaks is measured in a large cell population. However, the breakage pattern at the single-cell level indicates large discrepancies between the actions of the two agents. Irradiated cells show a uniform distribution of DNA strand breaks over the cell population. Effects of treatment with 30 micrograms x ml-1 BLM for 2 hr vary from practically zero in some cells to high levels of DNA strand breakage in others. Unlike the repair of radiation-induced DNA breaks, the repair efficiency of BLM-induced DNA strand breaks, as measured at the single-cell level, varies strongly among cells of the same population. Such heterogeneity at the cellular level potentially reduces BLM's usefulness for tumor therapy because the appearance of BLM-resistant subpopulations may critically impair treatment outcome.

scholarly journals Functional Organization of the Cardiac Ganglion of the Lobster, Homarus americanus

1973 ◽  
Vol 62 (4) ◽  
pp. 448-472 ◽  
Author(s):  
Earl Mayeri
Keyword(s):  
Spike Activity ◽  
Functional Organization ◽  
Large Cell ◽  
Homarus Americanus ◽  
Burst Activity ◽  
Small Cells ◽  
Cardiac Ganglion ◽  
Burst Pattern ◽  
Repetitive Electrical Stimulation ◽  
Stimulation Of

External recording and stimulation, techniques were used to determine which neurons and interactions are essential for production of the periodic burst discharge in the lobster cardiac ganglion. Burst activity can be modulated by brief single shocks applied to the four small cells, but not by similar stimulation of the five large cells, suggesting that normally one or more small cells primarily determine burst rate and duration. Repetitive electrical stimulation of large cells initiates spike activity in small cells, probably via excitatory synaptic and/or electrotonic connections which may normally act to prolong bursts and decrease burst rate. Transection of the ganglion can result in burst activity in small cells in the partial or complete absence of large cell spike activity, but large cells isolated from small cell excitatory synaptic input by transection or by application of dinitrophenol do not burst. Generally, transections which decrease excitatory feedback to small cells are accompanied by an increase in burst rate, but mean spike frequency over an entire burst cycle stabilizes at the original level within 10–30 min for various groups of cells whose spike-initiating sites are still intact. These and previous results suggest that the system is two layered: one or more small cells generate the burst pattern and impose it on the large cells which are the system's motorneurons.

scholarly journals Single-cell transcriptome provides novel insights into antler stem cells, a cell type capable of mammalian organ regeneration

2018 ◽  
Author(s):  
Hengxing Ba ◽  
Datao Wang ◽  
Weiyao Wu ◽  
Hongmei Sun ◽  
Chunyi Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Single Cell ◽  
Large Cell ◽  
Stem Cell Markers ◽  
Single Cell Level ◽  
Cell Type ◽  
Cell Level ◽  
Homogeneous Population ◽  
Organ Regeneration

AbstractAntler regeneration, a stem cell-based epimorphic process, has potential as a valuable model for regenerative medicine. A pool of antler stem cells (ASCs) for antler development is located in the antlerogenic periosteum (AP). However, whether this ASC pool is homogenous or heterogeneous has not been fully evaluated. In this study, we produced a comprehensive transcriptome dataset at the single-cell level for the ASCs based on the 10x Genomics platform (scRNA-seq). A total of 4,565 ASCs were sequenced and classified into a large cell cluster, indicating that the ASCs resident in the AP are likely to be a homogeneous population. The scRNA-seq data revealed that tumor-related genes were highly expressed in these homogeneous ASCs: i.e. TIMP1, TMSB10, LGALS1, FTH1, VIM, LOC110126017 and S100A4. Results of screening for stem cell markers suggest that the ASCs may be considered as a special type of stem cell between embryonic (CD9) and adult (CD29, CD90, NPM1 and VIM) stem cells. Our results provide the first comprehensive transcriptome analysis at the single-cell level for the ASCs, and identified only one major cell type resident in the AP and some key stem cell genes, which may hold the key to why antlers, the unique mammalian organ, can fully regenerate once lost.

scholarly journals Single-cell cytometry via multiplexed fluorescence prediction by label-free reflectance microscopy

2020 ◽  
Author(s):  
Shiyi Cheng ◽  
Sipei Fu ◽  
Yumi Mun Kim ◽  
Weiye Song ◽  
Yunzhe Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Structural Information ◽  
Large Cell ◽  
Label Free ◽  
Cell Cycles ◽  
Imaging Cytometry ◽  
Single Cell Profiling ◽  
The Rich ◽  
Reflectance Microscopy ◽  
Labeling Method

AbstractTraditional imaging cytometry uses fluorescence markers to identify specific structures, but is limited in throughput by the labeling process. Here we develop a label-free technique that alleviates the physical staining and provides highly multiplexed readouts via a deep learning-augmented digital labeling method. We leverage the rich structural information and superior sensitivity in reflectance microscopy and show that digital labeling predicts highly accurate subcellular features after training on immunofluorescence images. We demonstrate up to 3× improvement in the prediction accuracy over the state-of-the-art. Beyond fluorescence prediction, we demonstrate that single-cell level structural phenotypes of cell cycles are correctly reproduced by the digital multiplexed images, including Golgi twins, Golgi haze during mitosis and DNA synthesis. We further show that the multiplexed readouts enable accurate multi-parametric single-cell profiling across a large cell population. Our method can dramatically improve the throughput for imaging cytometry toward applications for phenotyping, pathology, and high-content screening.

scholarly journals Single-Cell Analysis Uncovers a Vast Diversity in Intracellular Viral Defective Interfering RNA Content Affecting the Large Cell-to-Cell Heterogeneity in Influenza A Virus Replication

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 71 ◽  
Author(s):  
Sascha Young Kupke ◽  
Lam-Ha Ly ◽  
Stefan Thomas Börno ◽  
Alexander Ruff ◽  
Bernd Timmermann ◽  
...  
Keyword(s):  
Single Cell ◽  
Influenza A Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Single Cell Analysis ◽  
Virus Production ◽  
Large Cell ◽  
Cell Heterogeneity ◽  
Viral Mrnas ◽  
Cell To Cell Variability

Virus replication displays a large cell-to-cell heterogeneity; yet, not all sources of this variability are known. Here, we study the effect of defective interfering (DI) particle (DIP) co-infection on cell-to-cell variability in influenza A virus (IAV) replication. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNA) and are, thus, defective in virus replication. Moreover, they interfere with virus replication. Using single-cell isolation and reverse transcription polymerase chain reaction, we uncovered a large between-cell heterogeneity in the DI vRNA content of infected cells, which was confirmed for DI mRNAs by single-cell RNA sequencing. A high load of intracellular DI vRNAs and DI mRNAs was found in low-productive cells, indicating their contribution to the large cell-to-cell variability in virus release. Furthermore, we show that the magnitude of host cell mRNA expression (some factors may inhibit virus replication), but not the ribosome content, may further affect the strength of single-cell virus replication. Finally, we show that the load of viral mRNAs (facilitating viral protein production) and the DI mRNA content are, independently from one another, connected with single-cell virus production. Together, these insights advance single-cell virology research toward the elucidation of the complex multi-parametric origin of the large cell-to-cell heterogeneity in virus infections.

Action Potential Initiation and Propagation in CA3 Pyramidal Axons

2007 ◽  
Vol 97 (5) ◽  
pp. 3460-3472 ◽  
Author(s):  
Julian P. Meeks ◽  
Steven Mennerick
Keyword(s):  
Sodium Channel ◽  
Conduction Velocity ◽  
Initiation Site ◽  
Initiation Zone ◽  
Initiation And Propagation ◽  
Threshold Crossing ◽  
Action Potential Initiation ◽  
Ca3 Neurons ◽  
Zone Characteristic ◽  
Spike Initiation

Thin, unmyelinated axons densely populate the mammalian hippocampus and cortex. However, the location and dynamics of spike initiation in thin axons remain unclear. We investigated basic properties of spike initiation and propagation in CA3 neurons of juvenile rat hippocampus. Sodium channel alpha subunit distribution and local applications of tetrodotoxin demonstrate that the site of first threshold crossing in CA3 neurons is ∼35 μm distal to the soma, somewhat more proximal than our previous estimates. This discrepancy can be explained by the finding, obtained with simultaneous whole cell somatic and extracellular axonal recordings, that a zone of axon stretching to ∼100 μm distal to the soma reaches a maximum rate of depolarization nearly synchronously by the influx of sodium from the high-density channels. Models of the proximal axon incorporating observed distributions of sodium channel staining recapitulated salient features of somatic and axonal spike waveforms, including the predicted initiation zone, characteristic spike latencies, and conduction velocity. The preferred initiation zone was unaltered by stimulus strength or repetitive spiking, but repetitive spiking increased threshold and significantly slowed initial segment recruitment time and conduction velocity. Our work defines the dynamics of initiation and propagation in hippocampal principal cell axons and may help reconcile recent controversies over initiation site in other axons.

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