scholarly journals Structure and function of axo-axonic inhibition

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Casey M Schneider-Mizell ◽  
Agnes L Bodor ◽  
Forrest Collman ◽  
Derrick Brittain ◽  
Adam Bleckert ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Large Scale ◽  
Cell Activity ◽  
Cell Types ◽  
Structural Features ◽  
Inhibitory Neurons ◽  
Target Cells ◽  
Population Activity ◽  
Chandelier Cells

Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.

scholarly journals Chandelier cell anatomy and function reveal a variably distributed but common signal

2020 ◽  
Author(s):  
Casey M. Schneider-Mizell ◽  
Agnes L. Bodor ◽  
Forrest Collman ◽  
Derrick Brittain ◽  
Adam A. Bleckert ◽  
...  
Keyword(s):  
Large Scale ◽  
Pyramidal Neurons ◽  
Cell Activity ◽  
Cortical Cell ◽  
Cell Types ◽  
Structural Features ◽  
Target Neuron ◽  
Chandelier Cell ◽  
Chandelier Cells

AbstractThe activity and connectivity of inhibitory cells has a profound impact on the operation of neuronal networks. While the average connectivity of many inhibitory cell types has been characterized, we still lack an understanding of how individual interneurons distribute their synapses onto their targets and how heterogeneous the inhibition is onto different individual excitatory neurons. Here, we use large-scale volumetric electron microscopy (EM) and functional imaging to address this question for chandelier cells in layer 2/3 of mouse visual cortex. Using dense morphological reconstructions from EM, we mapped the complete chandelier input onto 153 pyramidal neurons. We find that the number of input synapses is highly variable across the population, but the variability is correlated with structural features of the target neuron: soma depth, soma size, and the number of perisomatic synapses received. Functionally, we found that chandelier cell activity in vivo was highly correlated and tracks pupil diameter, a proxy for arousal state. We propose that chandelier cells provide a global signal whose strength is individually adjusted for each target neuron. This approach, combining comprehensive structural analysis with functional recordings of identified cell types, will be a powerful tool to uncover the wiring rules across the diversity of cortical cell types.

scholarly journals Perisomatic Inhibition and Its Relation to Epilepsy and to Synchrony Generation in the Human Neocortex

2021 ◽  
Vol 23 (1) ◽  
pp. 202
Author(s):  
Estilla Zsófia Tóth ◽  
Felicia Gyöngyvér Szabó ◽  
Ágnes Kandrács ◽  
Noémi Orsolya Molnár ◽  
Gábor Nagy ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cannabinoid Receptor ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Inhibitory Neurons ◽  
Inhibitory Input ◽  
Cortical Region ◽  
Interictal Spikes ◽  
Population Activity

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated—in conjunction with the electron microscopy—that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 118-119
Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun
Keyword(s):  
Electron Microscopy ◽  
Structural Organization ◽  
Cell Types ◽  
Structural Features ◽  
Molecular Architecture ◽  
The Past ◽  
Keratin Filaments ◽  
Different Types ◽  
10 Nm Filaments ◽  
Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

scholarly journals Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Que ◽  
David Lukacsovich ◽  
Wenshu Luo ◽  
Csaba Földy
Keyword(s):  
Large Scale ◽  
Cell Types ◽  
Rna Seq ◽  
Neuronal Identity ◽  
Parvalbumin Interneurons ◽  
Different Types ◽  
Parvalbumin Interneuron ◽  
Cam Profile ◽  
Developmental Domains

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.

scholarly journals Role of Luteal Glucocorticoid Metabolism during Maternal Recognition of Pregnancy in Women

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5769-5779 ◽  
Author(s):  
Michelle Myers ◽  
M. Christy Lamont ◽  
Sander van den Driesche ◽  
Nirmala Mary ◽  
K. Joo Thong ◽  
...  
Keyword(s):  
Cell Activity ◽  
Tissue Remodeling ◽  
Cell Types ◽  
Endocrine Gland ◽  
Steroidogenic Cell ◽  
Luteal Tissue ◽  
Maternal Recognition Of Pregnancy

The human corpus luteum (hCL) is an active, transient, and dynamic endocrine gland. It will experience extensive tissue and vascular remodeling followed by 1) demise of the whole gland without any apparent scarring or 2) maintenance of structural and functional integrity dependent on conceptus-derived human chorionic gonadotropin (hCG). Because cortisol has well-characterized roles in tissue remodeling and repair, we hypothesized that it may have a role in controlling luteal dissolution during luteolysis and would be locally produced toward the end of the luteal cycle. Glucocorticoid-metabolizing enzymes [11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2] and the glucocorticoid receptor (GR) were assessed in hCL and cultures of luteinized granulosa cells (LGC) using immunofluorescence and quantitative RT-PCR. Furthermore, the effect of cortisol on steroidogenic cell survival and fibroblast-like cell activity was explored in vitro. The hCL expressed 11βHSD isoenzymes in LGC and nuclear GR in several cell types. hCG up-regulated the expression and activity of 11βHSD type 1 (P < 0.05) and down-regulated type 2 enzyme (P < 0.05) in vitro and tended to do the same in vivo. Cortisol increased the survival of LGC treated with RU486 (P < 0.05) and suppressed the activity of a proteolytic enzyme associated with luteolysis in fibroblast-like cells (P < 0.05). Our results suggest that, rather than during luteolysis, it is luteal rescue with hCG that is associated with increased local cortisol generation by 11βHSD type 1. Locally generated cortisol may therefore act on the hCL through GR to have a luteotropic role in the regulation of luteal tissue remodeling during maternal recognition of pregnancy.

scholarly journals Exosome: A New Player in Translational Nanomedicine

2020 ◽  
Vol 9 (8) ◽  
pp. 2380 ◽  
Author(s):  
Houssam Aheget ◽  
María Tristán-Manzano ◽  
Loubna Mazini ◽  
Marina Cortijo-Gutierrez ◽  
Pablo Galindo-Moreno ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cell Types ◽  
Structural Features ◽  
Biologically Active ◽  
Biological Processes ◽  
New Approach ◽  
Current State ◽  
Exosome Biogenesis ◽  
Production Techniques

Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.

Solannm lyratum extract affected immune response in normal and leukemia murine animal in vivo

2010 ◽  
Vol 29 (5) ◽  
pp. 359-367 ◽  
Author(s):  
Jai-Sing Yang ◽  
Chia-Chun Wu ◽  
Chao-Lin Kuo ◽  
Chin-Chung Yeh ◽  
Fu-Shin Chueh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Folk Medicine ◽  
Cell Activity ◽  
Colon Adenocarcinoma ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Macrophage Phagocytosis

Solanum lyratum Thunberg (Solanaceae) has been used as a folk medicine for treating liver, lung and esophagus in the Chinese population. Our previous studies have shown that the crude extract of S. lyratum Thunberg (SLE) induced apoptosis in colo 205 human colon adenocarcinoma cells; however, there is no report to show SLE affect immune responses in vivo. In this study, the in vivo effects of SLE on leukemia WEHI-3 cells and immune responses such as phagocytosis and natural killer (NK) cell activity in normal and leukemia mice were investigated. The SLE treatment decreases surface markers of CD3 and Mac-3 in normal and leukemia mice but promoted the cell markers of CD19 and CD11b in normal mice and CD11b in leukemia mice indicating that the precursors of T cells was inhibited and B cells and macrophage were promoted. The SLE treatment promoted the activity of macrophage phagocytosis in the peripheral blood mononuclear cells (PBMC) and peritoneal cells from normal and leukemia mice. The results also showed that NK cells from the normal and leukemia mice after treatment with SLE can kill the YAC-1 target cells. Therefore, the SLE treatment increased macrophage and NK cell activities. These consistent results indicate SLE could be a potent immune responses agent.

scholarly journals STUDIES ON CHARACTERIZATION OF THE LYMPHOID TARGET CELL FOR ACTIVITY OF A THYMUS HUMORAL FACTOR

1973 ◽  
Vol 138 (1) ◽  
pp. 130-142 ◽  
Author(s):  
Varda Rotter ◽  
Amiela Globerson ◽  
Ichiro Nakamura ◽  
Nathan Trainin
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Cell Activity ◽  
Humoral Factor ◽  
Target Cells ◽  
Total Body ◽  
Thymus Cells ◽  
Marrow Cells

The immune response to SRBC was measured in the spleens of adult thymectomized, total body irradiated mice injected with various combinations of thymus and bone marrow cells together with thymic humoral factor (THF). It was found that the number of plaque-forming cells was significantly increased when THF was given in vivo immediately after thymus cell administration or when thymus cells were incubated in THF before injection. On the other hand, bone marrow cells equally treated did not manifest any T cell activity, since THF-treated bone marrow cells were not able to substitute thymus cells in the system used. The results accumulated in the present experiments indicate, therefore, that the target cells for THF activity are thymus cells which acquire a higher T helper cell capacity after THF treatment.

scholarly journals Contributions of Histamine, Prostanoids, and Neurokinins to Edema Elicited by Edema Toxin from Bacillus anthracis

2007 ◽  
Vol 75 (4) ◽  
pp. 1895-1903 ◽  
Author(s):  
Jeffrey Tessier ◽  
Candace Green ◽  
Diana Padgett ◽  
Wei Zhao ◽  
Lawrence Schwartz ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Cell Types ◽  
Vascular Leakage ◽  
Target Cells ◽  
Edema Factor ◽  
Edema Toxin ◽  
Neurokinin 1

ABSTRACT Bacillus anthracis edema toxin (ET), composed of protective antigen and an adenylate cyclase edema factor (EF), elicits edema in host tissues, but the target cells and events leading from EF-mediated cyclic-AMP production to edema are unknown. We evaluated the direct effect of ET on several cell types in vitro and tested the possibility that mediators of vascular leakage, such as histamine, contribute to edema in rabbits given intradermal ET. ET increased the transendothelial electrical resistance of endothelial monolayers, a response that is mechanistically inconsistent with the in vivo vascular leakage induced by ET. Screening of several drugs by intradermal treatment prior to toxin injection demonstrated reduced ET-induced vascular leakage with a cyclo-oxygenase inhibitor (indomethacin), agents that interfere with histamine (pyrilamine or cromolyn), or a neurokinin antagonist (spantide). Systemic administration of indomethacin or celecoxib (cyclo-oxygenase inhibitors), pyrilamine, aprepitant (a neurokinin 1 receptor antagonist), or indomethacin with pyrilamine significantly reduced vascular leakage associated with ET. Although the effects of pyrilamine, cromolyn, or aprepitant on ET-induced vascular leakage suggest a possible role for mast cells (MC) and sensory neurons in ET-induced edema, ET did not elicit degranulation of human skin MC or substance P release from NT2N cells in vitro. Our results indicate that ET, acting indirectly or directly on a target yet to be identified, stimulates the production/release of multiple inflammatory mediators, specifically neurokinins, prostanoids, and histamine. These mediators, individually and through complex interactions, increase vascular permeability, and interventions directed at these mediators may benefit hosts infected with B. anthracis.

scholarly journals Restricted replication of lentiviruses. Visna viruses induce a unique interferon during interaction between lymphocytes and infected macrophages.

1985 ◽  
Vol 162 (6) ◽  
pp. 1954-1969 ◽  
Author(s):  
O Narayan ◽  
D Sheffer ◽  
J E Clements ◽  
G Tennekoon
Keyword(s):  
Virus Replication ◽  
Cell Types ◽  
Target Cells ◽  
Host Animal ◽  
Restricted Type ◽  
Host Cell Interactions ◽  
Pathologic Lesions ◽  
Stage Process ◽  
Sudden Release

Lentivirus infections are characterized by a persistent, restricted type of virus replication in tissues. Using sheep and goat lentiviruses, whose target cells in vivo are macrophages, we explored virus-host cell interactions to determine whether an interferon (IFN) is produced during virus replication in vivo which causes restricted replication. We show that the lentiviruses were incapable of inducing IFN directly in any infected cell, including macrophages and lymphocytes. However, after infection with these viruses, sheep and goat macrophages acquired a factor that triggered IFN production by T lymphocytes. Only sheep/goat lentiviruses were capable of inducing the factor and, although these viruses replicated productively in various cell cultures of the natural host animal, only infected macrophages developed the IFN-inducing factor. The factor was produced continuously and was strictly cell associated, requiring direct contact with lymphocytes. The lymphocytes responded with a single, sudden release of IFN beginning 7 h after cocultivation and reaching peak values at 48 h, after which they ceased production and became refractory. IFN production was not immunologically specific and did not require histocompatibility between donors of the two cell types. The IFN is a nonglycosylated protein of molecular weight 54,000-64,000, and is stable to heat and acid treatments. These findings identify a unique IFN and a new method for virus induction of IFN. The novel two-stage process of induction provides a mechanism for local amplification and continuity of production of IFN in vivo. This is compatible with infection in the animal whose lentivirus-induced pathologic lesions consist of accumulations of lymphocytes and infected macrophages in target tissues.

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