scholarly journals Deciphering the contribution of oriens-lacunosum/moleculare (OLM) cells to intrinsic theta rhythms using biophysical local field potential (LFP) models

2018 ◽  
Author(s):  
Alexandra P. Chatzikalymniou ◽  
Frances K. Skinner
Keyword(s):  
Local Field ◽  
Average Power ◽  
Local Field Potentials ◽  
Field Potential ◽  
Cell Types ◽  
Field Potentials ◽  
Biophysical Modeling ◽  
Different Cell Types

AbstractOscillations in local field potentials (LFPs) commonly occur and analyses of them fuel brain function hypotheses. An understanding of the cellular correlates and pathways affecting LFPs is needed but many overlapping pathways in vivo makes this difficult to achieve. A prevalent LFP rhythm in the hippocampus is ‘theta’ (3-12 Hz). Theta rhythms emerge intrinsically in an in vitro whole hippocampus preparation and thus can be produced by local interactions between interneurons and pyramidal (PYR) cells. Overlapping pathways are much reduced in this preparation making it possible to decipher the contribution of different cell types to LFP generation. We focus on oriens-lacunosum/moleculare (OLM) cells as a major class of interneurons in the hippocampus. They can influence PYR cells through two distinct pathways, (i) by direct inhibition of PYR cell distal dendrites, and (ii) by indirect disinhibition of PYR cell proximal dendrites by inhibiting bistratified cells (BiCs) that target them. We use previous inhibitory network models and build biophysical LFP models using volume conductor theory. We assess the effect of OLM cells to ongoing intrinsic LFP theta rhythms by directly comparing our model LFP features with experiment. We find that robust LFP theta responses adhering to reproducible experimental criteria occur only for particular connectivities between OLM cells and BiCs. Decomposition of the LFP reveals that OLM cell inputs onto the PYR cell regulate robustness of LFP responses without affecting average power and that the robust response depends on co-activation of distal inhibition and basal excitation. We use our models to estimate the spatial extent of the region generating LFP theta rhythms, leading us to predict that about 22,000 PYR cells participate in generating the LFP theta rhythm. Besides allowing us to understand OLM cells’ contributions to intrinsic theta rhythms, our work can drive hypothesis developments of cellular contributions in vivo.Author SummaryOscillatory local field potentials (LFPs) are extracellularly recorded potentials that are widely used to interpret information processing in the brain. For example, theta LFP rhythms (3-12 Hz) are correlated with memory processing and it is known that particular inhibitory cell types control their existence. As such, it is critical for us to appreciate how various cell types contribute to the characteristics of LFP rhythms. A precise biophysical modeling scheme linking activity at the cellular level and the recorded signal has been established. However, it is difficult to assess cellular contributions in vivo because of many spatiotemporally overlapping pathways that prevent the unambiguous separation of signals. Using an in vitro preparation that exhibits intrinsic theta (3-12 Hz) rhythms and where there is much less overlap, we build biophysical LFP models to explore cell contributions to ongoing intrinsic theta rhythms. We uncover distinct contributions from different cell types and show that robust theta rhythms depend specifically on one of the cell types. We are able to determine this because our LFP models have direct links with experiment and we are able to perform thousands of simulations.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

scholarly journals Bromodomain protein inhibition: a novel therapeutic strategy in rheumatic diseases

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000744 ◽  
Author(s):  
Kerstin Klein
Keyword(s):  
Animal Models ◽  
Rheumatic Diseases ◽  
Transcriptional Activation ◽  
Therapeutic Strategy ◽  
Cell Types ◽  
Protein Inhibition ◽  
Different Cell Types ◽  
Novel Therapeutic

The reading of acetylation marks on histones by bromodomain (BRD) proteins is a key event in transcriptional activation. Small molecule inhibitors targeting bromodomain and extra-terminal (BET) proteins compete for binding to acetylated histones. They have strong anti-inflammatory properties and exhibit encouraging effects in different cell types in vitro and in animal models resembling rheumatic diseases in vivo. Furthermore, recent studies that focus on BRD proteins beyond BET family members are discussed.

scholarly journals Filopodyan: An open-source pipeline for the analysis of filopodia

2017 ◽  
Vol 216 (10) ◽  
pp. 3405-3422 ◽  
Author(s):  
Vasja Urbančič ◽  
Richard Butler ◽  
Benjamin Richier ◽  
Manuel Peter ◽  
Julia Mason ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Dynamic Properties ◽  
Cell Types ◽  
Molecular Heterogeneity ◽  
Interactive Editing ◽  
Motile Cells ◽  
Different Cell Types ◽  
Neuronal Growth Cones

Filopodia have important sensory and mechanical roles in motile cells. The recruitment of actin regulators, such as ENA/VASP proteins, to sites of protrusion underlies diverse molecular mechanisms of filopodia formation and extension. We developed Filopodyan (filopodia dynamics analysis) in Fiji and R to measure fluorescence in filopodia and at their tips and bases concurrently with their morphological and dynamic properties. Filopodyan supports high-throughput phenotype characterization as well as detailed interactive editing of filopodia reconstructions through an intuitive graphical user interface. Our highly customizable pipeline is widely applicable, capable of detecting filopodia in four different cell types in vitro and in vivo. We use Filopodyan to quantify the recruitment of ENA and VASP preceding filopodia formation in neuronal growth cones, and uncover a molecular heterogeneity whereby different filopodia display markedly different responses to changes in the accumulation of ENA and VASP fluorescence in their tips over time.

scholarly journals Insulin and Analogue Effects on Protein Degradation in Different Cell Types

2000 ◽  
Vol 276 (15) ◽  
pp. 11552-11558 ◽  
Author(s):  
Janet Fawcett ◽  
Frederick G. Hamel ◽  
Robert G. Bennett ◽  
Zoltan Vajo ◽  
William C. Duckworth
Keyword(s):  
Protein Degradation ◽  
Hepg2 Cells ◽  
Cell Types ◽  
Major Effect ◽  
Cellular Protein ◽  
Experimental Conditions ◽  
L6 Cells ◽  
Different Cell Types

In adult animals, the major effect of insulin on protein turnover is inhibition of protein degradation. Cellular protein degradation is under the control of multiple systems, including lysosomes, proteasomes, calpains, and giant protease. Insulin has been shown to alter proteasome activityin vitroandin vivo. We examined the inhibition of protein degradation by insulin and insulin analogues (LysB28,ProB29-insulin (LysPro), AspB10-insulin (B10), and GluB4,GlnB16,PheB17-insulin (EQF)) in H4, HepG2, and L6 cells. These effects were compared with receptor binding. Protein degradation was examined by release of trichloroacetic acid-soluble radioactivity from cells previously labeled with [3H]leucine. Short- and intermediate-lived proteins were examined. H4 cells bound insulin with an EC50of 4.6 × 10−9m. LysPro was similar. The affinity of B10 was increased 2-fold; that of EQF decreased 15-fold. Protein degradation inhibition in H4 cells was highly sensitive to insulin (EC50= 4.2 × 10−11and 1.6 × 10−10m, short- and intermediate-lived protein degradation, respectively) and analogues. Despite similar binding, LysPro was 11- to 18-fold more potent than insulin at inhibiting protein degradation. Conversely, although EQF showed lower binding to H4 cells than insulin, its action was similar. The relative binding potencies of analogues in HepG2 cells were similar to those in H4 cells. Examination of protein degradation showed insulin, LysPro, and B10 were equivalent while EQF was less potent. L6 cells showed no difference in the binding of the analogues compared with insulin, but their effect on protein degradation was similar to that seen in HepG2 cells except B10 inhibited intermediate-lived protein degradation better than insulin. These studies illustrate the complexities of cellular protein degradation and the effects of insulin. The effect of insulin and analogues on protein degradation vary significantly in different cell types and with different experimental conditions. The differences seen in the action of the analogues cannot be attributed to binding differences. Post-receptor mechanisms, including intracellular processing and degradation, must be considered.

scholarly journals A Spatio-Temporal Model and Inference Tools for Longitudinal Count Data on Multicolor Cell Growth

2018 ◽  
Vol 14 (2) ◽  
Author(s):  
PuXue Qiao ◽  
Christina Mølck ◽  
Davide Ferrari ◽  
Frédéric Hollande
Keyword(s):  
Cell Growth ◽  
Image Data ◽  
Real Data ◽  
Cell Types ◽  
Spatial Autoregressive ◽  
Spatio Temporal ◽  
Different Cell Types ◽  
Temporal Interactions

AbstractMulticolor cell spatio-temporal image data have become important to investigate organ development and regeneration, malignant growth or immune responses by tracking different cell types both in vivo and in vitro. Statistical modeling of image data from common longitudinal cell experiments poses significant challenges due to the presence of complex spatio-temporal interactions between different cell types and difficulties related to measurement of single cell trajectories. Current analysis methods focus mainly on univariate cases, often not considering the spatio-temporal effects affecting cell growth between different cell populations. In this paper, we propose a conditional spatial autoregressive model to describe multivariate count cell data on the lattice, and develop inference tools. The proposed methodology is computationally tractable and enables researchers to estimate a complete statistical model of multicolor cell growth. Our methodology is applied on real experimental data where we investigate how interactions between cancer cells and fibroblasts affect their growth, which are normally present in the tumor microenvironment. We also compare the performance of our methodology to the multivariate conditional autoregressive (MCAR) model in both simulations and real data applications.

scholarly journals The Tuberculous Granuloma: An Unsuccessful Host Defence Mechanism Providing a Safety Shelter for the Bacteria?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mayra Silva Miranda ◽  
Adrien Breiman ◽  
Sophie Allain ◽  
Florence Deknuydt ◽  
Frederic Altare
Keyword(s):  
Cell Types ◽  
Giant Cells ◽  
The Body ◽  
Differentiated Cells ◽  
Latently Infected ◽  
Long Time ◽  
Infectious Stage ◽  
Different Cell Types

One of the main features of the immune response toM. Tuberculosisis the formation of an organized structure called granuloma. It consists mainly in the recruitment at the infectious stage of macrophages, highly differentiated cells such as multinucleated giant cells, epithelioid cells and Foamy cells, all these cells being surrounded by a rim of lymphocytes. Although in the first instance the granuloma acts to constrain the infection, some bacilli can actually survive inside these structures for a long time in a dormant state. For some reasons, which are still unclear, the bacilli will reactivate in 10% of the latently infected individuals, escape the granuloma and spread throughout the body, thus giving rise to clinical disease, and are finally disseminated throughout the environment. In this review we examine the process leading to the formation of the granulomatous structures and the different cell types that have been shown to be part of this inflammatory reaction. We also discuss the differentin vivoandin vitromodels available to study this fascinating immune structure.

scholarly journals Modulation of In Vivo Migratory Function of α2β1 Integrin in Mouse Liver

1997 ◽  
Vol 8 (10) ◽  
pp. 1863-1875 ◽  
Author(s):  
Wai-chi Ho ◽  
Christine Heinemann ◽  
Dolores Hangan ◽  
Shashi Uniyal ◽  
Vincent L. Morris ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Cell Movement ◽  
Liver Parenchyma ◽  
Cell Types ◽  
Optimal Level ◽  
Matrix Proteins ◽  
Different Cell Types ◽  
Α2β1 Integrin

We report herein that expression of α2β1 integrin increased human erythroleukemia K562 transfectant (KX2C2) cell movement after extravasation into liver parenchyma. In contrast, a previous study demonstrated that α2β1 expression conferred a stationary phenotype to human rhabdomyosarcoma RD transfectant (RDX2C2) cells after extravasation into the liver. We therefore assessed the adhesive and migratory function of α2β1 on KX2C2 and RDX2C2 cells using a α2β1-specific stimulatory monoclonal antibody (mAb), JBS2, and a blocking mAb, BHA2.1. In comparison with RDX2C2 cells, KX2C2 were only weakly adherent to collagen and laminin. JBS2 stimulated α2β1-mediated interaction of KX2C2 cells with both collagen and laminin resulting in increases in cell movement on both matrix proteins. In the presence of Mn2+, JBS2-stimulated adhesion on collagen beyond an optimal level for cell movement. In comparison, an increase in RDX2C2 cell movement on collagen required a reduction in its adhesive strength provided by the blocking mAb BHA2.1. Consistent with these in vitro findings, in vivo videomicroscopy revealed that α2β1-mediated postextravasation cell movement of KX2C2 cells in the liver tissue could also be stimulated by JBS2. Thus, results demonstrate that α2β1 expression can modulate postextravasation cell movement by conferring either a stationary or motile phenotype to different cell types. These findings may be related to the differing metastatic activities of different tumor cell types.

A method for recording evoked local field potentials in the primate dentate gyrus in vivo

Hippocampus ◽  
2011 ◽  
Vol 21 (5) ◽  
pp. 565-574 ◽  
Author(s):  
Ryoi Tamura ◽  
Satoshi Eifuku ◽  
Teruko Uwano ◽  
Michiya Sugimori ◽  
Kumiko Uchiyama ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Local Field ◽  
Local Field Potentials ◽  
Field Potentials
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