scholarly journals Kv1 channels regulate variations in spike patterning and temporal reliability in the avian cochlear nucleus angularis

2021 ◽  
Author(s):  
James F Baldassano ◽  
Katrina M. MacLeod
Keyword(s):  
Cochlear Nucleus ◽  
Temporal Structure ◽  
Potassium Conductance ◽  
Neuronal Population ◽  
Temporal Properties ◽  
Specific Subset ◽  
Key Factor ◽  
Channel Expression ◽  
Nucleus Angularis

Diverse physiological phenotypes in a neuronal population can broaden the range of computational capabilities within a brain region. The avian cochlear nucleus angularis (NA) contains a heterogeneous population of neurons whose variation in intrinsic properties results in electrophysiological phenotypes with a range of sensitivities to temporally modulated input. The low-threshold potassium conductance (GKLT) is a key feature of neurons involved in fine temporal structure coding for sound localization but a role for these channels in intensity or spectrotemporal coding has not been established. To determine whether GKLT affects the phenotypical variation and temporal properties of NA neurons, we applied dendrotoxin (DTX), a potent antagonist of Kv1-type potassium channels, to chick brain stem slices in vitro during whole-cell patch clamp recordings. We found a cell-type specific subset of NA neurons were sensitive to DTX: single-spiking NA neurons were most profoundly affected, as well as a subset of tonic firing neurons. Both tonic I (phasic onset bursting) and tonic II (delayed firing) neurons showed DTX sensitivity in their firing rate and phenotypical firing pattern. Tonic III neurons were unaffected. Spike time reliability and fluctuation sensitivity measured in DTX-sensitive NA neurons was also reduced with DTX. Finally, DTX reduced spike threshold adaptation in these neurons, suggesting that GKLT contributes to the temporal properties that allow coding of rapid changes in the inputs to NA neurons. These results suggest that variation in Kv1 channel expression may be a key factor in functional diversity in the avian cochlear nucleus.

scholarly journals Kv1 channels regulate variations in spike patterning and temporal reliability in the avian cochlear nucleus angularis

2021 ◽  
Author(s):  
James F Baldassano ◽  
Katrina M MacLeod
Keyword(s):  
Cochlear Nucleus ◽  
Temporal Structure ◽  
Potassium Conductance ◽  
Neuronal Population ◽  
Temporal Properties ◽  
Specific Subset ◽  
Key Factor ◽  
Channel Expression ◽  
Nucleus Angularis

Diverse physiological phenotypes in a neuronal population can broaden the range of computational capabilities within a brain region. The avian cochlear nucleus angularis (NA) contains a heterogeneous population of neurons whose variation in intrinsic properties results in electrophysiological phenotypes with a range of sensitivities to temporally modulated input. The low-threshold potassium conductance (GKLT) is a key feature of neurons involved in fine temporal structure coding for sound localization but a role for these channels in intensity or spectrotemporal coding has not been established. To determine whether GKLT affects the phenotypical variation and temporal properties of NA neurons, we applied dendrotoxin (DTX), a potent antagonist of Kv1-type potassium channels, to chick brain stem slices in vitro during whole-cell patch clamp recordings. We found a cell-type specific subset of NA neurons were sensitive to DTX: single-spiking NA neurons were most profoundly affected, as well as a subset of tonic firing neurons. Both tonic I (phasic onset bursting) and tonic II (delayed firing) neurons showed DTX sensitivity in their firing rate and phenotypical firing pattern. Tonic III neurons were unaffected. Spike time reliability and fluctuation sensitivity measured in DTX-sensitive NA neurons was also reduced with DTX. Finally, DTX reduced spike threshold adaptation in these neurons, suggesting that GKLT contributes to the temporal properties that allow coding of rapid changes in the inputs to NA neurons. These results suggest that variation in Kv1 channel expression may be a key factor in functional diversity in the avian cochlear nucleus.

scholarly journals Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons

2012 ◽  
Vol 107 (11) ◽  
pp. 3008-3019 ◽  
Author(s):  
Ricardo M. Leao ◽  
Shuang Li ◽  
Brent Doiron ◽  
Thanos Tzounopoulos
Keyword(s):  
Cochlear Nucleus ◽  
Pyramidal Neurons ◽  
Sensory Information ◽  
Potassium Conductance ◽  
Neuronal Population ◽  
Dorsal Cochlear Nucleus ◽  
Resting Membrane Potential ◽  
Maximal Conductance ◽  
Biophysical Mechanism ◽  
Inwardly Rectifying

Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nucleus, where principal neurons exist in two qualitatively distinct states: spontaneously active or not spontaneously active. Our studies reveal that distinct activity states are generated by the differential levels of a Ba2+-sensitive, inwardly rectifying potassium conductance (Kir). Variability in Kir maximal conductance causes variations in the resting membrane potential (RMP). Low Kir conductance depolarizes RMP to voltages above the threshold for activating subthreshold-persistent sodium channels (Nap). Once Nap channels are activated, the RMP becomes unstable, and spontaneous firing is triggered. Our results provide a biophysical mechanism for generating neural heterogeneity, which may play a role in the encoding of sensory information.

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.

scholarly journals POS0393 FIBRIN DEPOSITION IS AN ACTIVE TRIGGER OF CARTILAGE DEGENERATION IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 426.1-426
Author(s):  
T. Hügle ◽  
S. Nasi ◽  
D. Ehirchiou ◽  
P. Omoumi ◽  
A. So ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Cartilage Explants ◽  
Fibrin Deposition ◽  
Qrt Pcr ◽  
Catabolic Genes ◽  
Key Factor ◽  
Calcific Deposits

Background:Fibrin(ogen) maintains inflammation in various disorders but has never been linked to cartilage damage in rheumatoid arthritis (RA) or other forms of inflammatory arthritis.Objectives:To investigate the role of fibrin deposition on cartilage integrity in arthritis.Methods:Fibrin deposition on knee cartilage was analyzed by immunohistochemistry in RA patients and in murine adjuvant-induced arthritis (AIA). In chondrocytes, fibrinogen expression (Fgα, Fgβ, Fgγ) and procoagulant activity were evaluated by qRT-PCR and turbidimetry respectively. Fibrin-induced catabolic genes were assessed by qRT-PCR in chondrocytes. Fibrin-mediated chondro-synovial adhesion (CSA) with subsequent cartilage tears was studied in co-cultures of human RA cartilage with autologous synoviocytes, in the AIA model, and by MRI. The link between fibrin and calcification was examined in human RA cartilage stained for calcific deposits and in vitro in fibrinogen-stimulated chondrocytes.Results:Fibrin deposition on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA wildtype (WT) mice, while fibrinogen deficient (Fg-/-) mice were protected. Accordingly, fibrin upregulated catabolic enzymes (Adamts5 and Mmp13) in chondrocytes. Secondly, CSA was present in fibrin-rich and damaged cartilage in AIA WT but not in Fg-/- mice. In line, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-positive degraded areas. Gadolinium-enhanced MRI of human joints showed contrast-enhancement along cartilage surface in RA patients but not in controls. Finally, fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization inducing pro-calcification genes (Anx5, Pit1, Pc1) and cytokine (IL-6). Although at a much lesser extent, we observed similar fibrin-mediated mechanisms in osteoarthritis (OA).Conclusion:Fibrin deposition directly impacts on cartilage integrity via induction of catabolism, mechanical stress, and calcification. Potentially, fibrin is a key factor of cartilage damage occurring in RA as a secondary consequence of inflammation.Disclosure of Interests:None declared

Spatio-temporal visual properties in the ascending tectofugal system

2010 ◽  
Vol 5 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Alice Rokszin ◽  
Zita Márkus ◽  
Gábor Braunitzer ◽  
Antal Berényi ◽  
Marek Wypych ◽  
...  
Keyword(s):  
Visual Information ◽  
Frequency Tuning ◽  
Temporal Frequency ◽  
Neuronal Population ◽  
Neuronal Responses ◽  
Temporal Properties ◽  
Visual Receptive Field ◽  
Detailed Statistical Analysis ◽  
Spatio Temporal ◽  
Visual Properties

AbstractOur study compares the spatio-temporal visual receptive field properties of different subcortical stages of the ascending tectofugal visual system. Extracellular single-cell recordings were performed in the superficial (SCs) and intermediate (SCi) layers of the superior colliculus (SC), the suprageniculate nucleus (Sg) of the posterior thalamus and the caudate nucleus (CN) of halothane-anesthetized cats. Neuronal responses to drifting gratings of various spatial and temporal frequencies were recorded. The neurons of each structure responded optimally to low spatial and high temporal frequencies and displayed narrow spatial and temporal frequency tuning. The detailed statistical analysis revealed that according to its stimulus preferences the SCs has markedly different spatio-temporal properties from the homogeneous group formed by the SCi, Sg and CN. The SCs neurons preferred higher spatial and lower temporal frequencies and had broader spatial tuning than the other structures. In contrast to the SCs the visually active SCi, as well as the Sg and the CN neurons possessed consequently similar spatio-temporal preferences. These data support our hypothesis that the visually active SCi, Sg and CN neurons form a homogeneous neuronal population given a similar spatio-temporal frequency preference and a common function in processing of dynamic visual information.

scholarly journals Kiss1 Neurons Drastically Change Their Firing Activity in Accordance With the Reproductive State: Insights From a Seasonal Breeder

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4868-4880 ◽  
Author(s):  
Masaharu Hasebe ◽  
Shinji Kanda ◽  
Hiroyuki Shimada ◽  
Yasuhisa Akazome ◽  
Hideki Abe ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Resting Membrane Potential ◽  
Reproductive State ◽  
Firing Patterns ◽  
State Dependent ◽  
Channel Expression ◽  
Physiological Analysis ◽  
Seasonal Breeder ◽  
Green Fluorescent

Kisspeptin (Kiss) neurons show drastic changes in kisspeptin expression in response to the serum sex steroid concentration in various vertebrate species. Thus, according to the reproductive states, kisspeptin neurons are suggested to modulate various neuronal activities, including the regulation of GnRH neurons in mammals. However, despite their reproductive state-dependent regulation, there is no physiological analysis of kisspeptin neurons in seasonal breeders. Here we generated the first kiss1-enhanced green fluorescent protein transgenic line of a seasonal breeder, medaka, for histological and electrophysiological analyses using a whole-brain in vitro preparation in which most synaptic connections are intact. We found histologically that Kiss1 neurons in the nucleus ventralis tuberis (NVT) projected to the preoptic area, hypothalamus, pituitary, and ventral telencephalon. Therefore, NVT Kiss1 neurons may regulate various homeostatic functions and innate behaviors. Electrophysiological analyses revealed that they show various firing patterns, including bursting. Furthermore, we found that their firings are regulated by the resting membrane potential. However, bursting was not induced from the other firing patterns with a current injection, suggesting that it requires some chronic modulations of intrinsic properties such as channel expression. Finally, we found that NVT Kiss1 neurons drastically change their neuronal activities according to the reproductive state and the estradiol levels. Taken together with the previous reports, we here conclude that the breeding condition drastically alters the Kiss1 neuron activities in both gene expression and firing activities, the latter of which is strongly related to Kiss1 release, and the Kiss1 peptides regulate the activities of various neural circuits through their axonal projections.

scholarly journals Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Cristian Doñas ◽  
Macarena Fritz ◽  
Valeria Manríquez ◽  
Gabriela Tejón ◽  
María Rosa Bono ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Trichostatin A ◽  
Gene Promoter ◽  
Treg Cells ◽  
Specific Subset ◽  
Global Increase ◽  
And Function ◽  
H3 Acetylation

Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that thefoxp3gene promoter becomes hyperacetylated inin vitrodifferentiated Tregs compared to naïve CD4+T cells. We also show that the histone deacetylase inhibitor TSA stimulated thein vitrodifferentiation of naïve CD4+T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+Treg cells.

scholarly journals Idiotypic analysis of potential and available repertoires in the arsonate system.

1984 ◽  
Vol 160 (1) ◽  
pp. 1-11 ◽  
Author(s):  
M Slaoui ◽  
O Leo ◽  
J Marvel ◽  
M Moser ◽  
J Hiernaux ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cells ◽  
Keyhole Limpet Hemocyanin ◽  
High Frequencies ◽  
Specific Subset ◽  
A Minor ◽  
Very High Frequencies ◽  
Very High ◽  
Limiting Dilution

We have shown that, by suitable idiotypic manipulation, BALB/c mice can express the major cross-reactive idiotype (CRI) of A/J mice in response to azophenylarsonate (Ars). In order to know if the CRIA idiotype is present in the potential repertoire of BALB/c before any intentional selection, we used polyclonal activation in vitro and limiting dilution analysis. The readout was done with two monoclonal anti-CRIA antibodies that recognize distinct idiotopes on a CRIA+ A/J germline-encoded monoclonal antibody. We studied the frequency of CRIA+ lipopolysaccharide (LPS)-reactive cells in the spleens of nonimmune and immune A/J mice and in the spleens of naive and manipulated (i.e., producing CRIA+ antibodies) BALB/c mice. A/J and BALB/c naive individuals presented very high frequencies of Ars-specific B cells while the frequency of CRIA+ B cells was only a minor subset (0.5%) of the total Ars-specific subset in the two strains. When A/J mice were immunized with Ars-keyhole limpet hemocyanin, a clear preferential expansion of the CRIA+ minor subset of A/J mice was observed (100x). No such enhancement was observed in BALB/c mice similarly treated. Manipulated BALB/c mice presented a higher frequency of CRIA+ anti-Ars B cells than naive or antigen-immunized BALB/c individuals.

scholarly journals Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinxin Yang ◽  
Haibo Yang ◽  
Fengdi Wu ◽  
Zhipeng Qi ◽  
Jiashuo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Dependent Manner ◽  
Protein Levels ◽  
Key Factor ◽  
Protein Sulfhydryl ◽  
Mrna And Protein Expression ◽  
The Brain

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.

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