Temporal covariance of pre- and postsynaptic activity regulates functional connectivity in the visual cortex

1994 ◽  
Vol 71 (4) ◽  
pp. 1403-1421 ◽  
Author(s):  
Y. Fregnac ◽  
J. P. Burke ◽  
D. Smith ◽  
M. J. Friedlander
Keyword(s):  
Visual Cortex ◽  
Brain Slices ◽  
Low Frequency ◽  
Stimulation Site ◽  
Independent Manner ◽  
In Vivo Experiments ◽  
Postsynaptic Activity ◽  
Series Of Experiments

1. It has been suggested from mathematical models and in vivo experiments in the visual cortex that periods of temporal covariance of pre- and postsynaptic activity can lead to a potentiation or depression of synaptic efficacy. We directly tested this hypothesis in vitro in the guinea pig and cat visual cortex. 2. Intracellular recordings were made in brain slices from 63 neurons in layers 2-4 in bicuculline-free artificial cerebrospinal fluid. Twenty-nine cells (n = 25 from pigmented guinea pigs and 4 from cats) were taken through a complete series of control and test protocols to evaluate the covariance hypothesis. Some (n = 7) cells that were taken through the complete experimental protocols were also filled intracellularly with biocytin. Compound postsynaptic potentials (PSPs) were evoked by low-frequency (0.2-1.0 Hz), weak (20% of threshold intensity) stimulation of the cortical white matter and/or intracortical sites in layers 2-3. 3. In one series of experiments we paired PSPs with imposed coincident depolarizing (S+) or hyperpolarizing (S-) pulses (mean +/- 2.8 nA for 50-80 ms) of the postsynaptic neuron (n = 54 PSPs; > 1 pairing protocol was often run on an individual cell). Controls consisted of analyzing the same number of S+ or S- pairings but with long temporal delays [called fixed delay pairings (FDPs)] between the test pathway stimulation and the onset of the intracellular current pulse (120 ms) and pseudopairings (PP) consisting of evoked PSPs and delivery of intracellular current injection pulses in a phase-independent manner. Twenty-one of 54 PSPs subjected to pairing were significantly modified by the protocol. The S+ protocol significantly (P < 0.05, Kolmogorov-Smirnov test) increased the peak amplitudes of 8 of 22 PSPs (+20 to +55%); the S- protocol significantly decreased the peak amplitudes of 13 of 32 PSPs (-15 to -88%), whereas the FDP and PP protocols generally did not cause significant changes in the PSPs (0% and 4%, respectively). Significant changes in PSPs persisted in most cases for 10-20 min. 4. Another series of experiments consisted of evaluating for the same cell the effects of evoking a PSP from one stimulation site without concomitant postsynaptic activation and alternately evoking a PSP from the other stimulation site with S+ or S- pairing (n = 25 PSPs). Only the paired pathway showed the predicted effects on the PSP (S+ pairing causing an increase in peak PSP amplitude and S- pairing causing a decrease in peak PSP amplitude).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Spontaneous and Perturbational Complexity in Cortical Cultures

2021 ◽  
Vol 11 (11) ◽  
pp. 1453
Author(s):  
Ilaria Colombi ◽  
Thierry Nieus ◽  
Marcello Massimini ◽  
Michela Chiappalone
Keyword(s):  
Cortical Neurons ◽  
Low Frequency ◽  
Initial Response ◽  
Moderate Increase ◽  
Electrode Arrays ◽  
In Vivo Experiments ◽  
Cortical Cultures ◽  
Cortical Slices

Dissociated cortical neurons in vitro display spontaneously synchronized, low-frequency firing patterns, which can resemble the slow wave oscillations characterizing sleep in vivo. Experiments in humans, rodents, and cortical slices have shown that awakening or the administration of activating neuromodulators decrease slow waves, while increasing the spatio-temporal complexity of responses to perturbations. In this study, we attempted to replicate those findings using in vitro cortical cultures coupled with micro-electrode arrays and chemically treated with carbachol (CCh), to modulate sleep-like activity and suppress slow oscillations. We adapted metrics such as neural complexity (NC) and the perturbational complexity index (PCI), typically employed in animal and human brain studies, to quantify complexity in simplified, unstructured networks, both during resting state and in response to electrical stimulation. After CCh administration, we found a decrease in the amplitude of the initial response and a marked enhancement of the complexity during spontaneous activity. Crucially, unlike in cortical slices and intact brains, PCI in cortical cultures displayed only a moderate increase. This dissociation suggests that PCI, a measure of the complexity of causal interactions, requires more than activating neuromodulation and that additional factors, such as an appropriate circuit architecture, may be necessary. Exploring more structured in vitro networks, characterized by the presence of strong lateral connections, recurrent excitation, and feedback loops, may thus help to identify the features that are more relevant to support causal complexity.

scholarly journals Circular RNA UBE2Q2 promotes malignant progression of gastric cancer by regulating signal transducer and activator of transcription 3-mediated autophagy and glycolysis

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Jing Yang ◽  
Xing Zhang ◽  
Jiacheng Cao ◽  
Penghui Xu ◽  
Zetian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Rna Binding ◽  
Synergistic Effects ◽  
Circular Rna ◽  
Circular Rnas ◽  
In Vivo Experiments ◽  
Series Of Experiments ◽  
Transcription 3

AbstractGastric cancer remains the third leading cause of cancer-related mortality worldwide. Emerging evidence has shown that circular RNAs (circRNAs) play a critical regulatory role in the occurrence and development of various cancers through sponging miRNAs or acting as RNA-binding protein (RBP) sponges. We found that circUBE2Q2 was significantly upregulated in GC tissues and cell lines. Knockdown of circUBE2Q2 inhibited proliferation, migration, invasion, and glycolysis, and increased autophagy in vitro. In addition, knockdown of circUBE2Q2 inhibited GC tumorigenicity and metastasis potential in vivo. A series of experiments were performed to confirm that circUBE2Q2 regulates GC progression via the circUBE2Q2-miR-370-3p-STAT3 axis and promotes tumor metastasis through exosomal communication. Further in vivo experiments confirmed that, combination treatment of circUBE2Q2 knocking down and STAT3 inhibitor has synergistic effects on the gastric cancer growth inhibition, which provides a possibility to enhance the sensitivity of targeted drugs to gastric cancer through targeting circUBE2Q2. Our findings revealed that circUBE2Q2 may serve as a new proliferation-promoting factor and prognostic marker in gastric cancer.

scholarly journals Potential Role of Synaptic Activity to Inhibit LTD Induction in Rat Visual Cortex

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Matthew R. Stewart ◽  
Hans C. Dringenberg
Keyword(s):  
Visual Cortex ◽  
Low Frequency ◽  
Synaptic Activity ◽  
Brain State ◽  
Complex Activity ◽  
Intact Brain ◽  
Frequency Stimulation ◽  
Cortical Synapses

Long-term depression (LTD), a widely studied form of activity-dependent synaptic plasticity, is typically induced by prolonged low-frequency stimulation (LFS). Interestingly, LFS is highly effective in eliciting LTDin vitro, but much less so underin vivoconditions; the reasons for the resistance of the intact brain to express LTD are not well understood. We examined if levels of background electrocorticographic (ECoG) activity influence LTD induction in the thalamocortical visual system of rats under very deep urethane anesthesia, inducing a brain state of reduced spontaneous cortical activity. Under these conditions, LFS applied to the lateral geniculate nucleus resulted in LTD of field postsynaptic potentials (fPSPs) recorded in the primary visual cortex (V1). Pairing LFS with stimulation of the brainstem (pedunculopontine) reticular formation resulted in the appearance of faster, more complex activity in V1 and prevented LTD induction, an effect that did not require muscarinic or nicotinic receptors. Reticular stimulation alone (without LFS) had no effect on cortical fPSPs. These results show that excitation of the brainstem activating system blocks the induction of LTD in V1. Thus, higher levels of neural activity may inhibit depression at cortical synapses, a hypothesis that could explain discrepancies regarding LTD induction in previousin vivoandin vitrowork.

LACK OF CELLULAR PRION PROTEIN UNMASKS NMDA NR2D SUBUNIT RECEPTOR FUNCTION WITH CONSEQUENCES TOWARD SYNAPTIC TRANSMISSION AND EXCITOTOXICITY

2008 ◽  
Vol 31 (4) ◽  
pp. 14
Author(s):  
H Khosravani ◽  
Y Zhang ◽  
S Tsutsui ◽  
S Hameed ◽  
C Altier ◽  
...  
Keyword(s):  
Cell Death ◽  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Brain Slices ◽  
Cellular Prion Protein ◽  
Receptor Function ◽  
In Vivo Experiments ◽  
Deactivation Kinetics

Background: The physiological functions of endogenous cellular prion protein (PrPC)is incompletely understood. Previously, it has been shown that PrP-null mice exhibit reduced long-term (synaptic) potentiation and greater susceptibility to seizure mortality in several in vivo models of epilepsy. In addition, PrP-null neurons in culture exhibit greater excito toxic cell death in response to kainic acid exposure, and in several models of oxidative stress. Although PrP seems toplay a protective role against various forms of cellular insults, the precise mechanism of such action is unknown. Methods: We investigated the synaptic properties of WT and PrP-null mice using cultured neurons and also brain slices from adult mice. Synaptic activity was assessed using whole-cell voltage clamp. We recorded spontaneous and evoked synaptic potentials. Extracellular field recordings of brain slices were also performed. Pharmacological agents were used to isolate all components of glutamatergic and GABA(A) mediated synaptic transmission. In addition, weassessed the effect of NMDA excitotoxicity in WT and PrP-null neurons using in vitro and in vivo experiments. We also used immunostaining, coimmunoprecipitation, and protein expression studies to quantify the relation between NMDA subtype expression and localization relative to native PrP. Results: Recordings in the CA1 layer of adult hippocampal slices showed thatPrP-null mice exhibit a reduced threshold to evoked responses, exhibited basal hyperexcitability, and in a model of zero-Mg2+ seizures also showed lower seizure threshold. No differences were observed in paired-pulse facilitation relative to WT animals. Recordings from mature hippocampal cultures showed slightly altered AMPA and GABAA miniature synaptic currents. NMDA mEPSCs were observed to be increased in amplitude and significantly prolonged in decaytime. NMDA-evoked currents also exhibited markedly prolonged deactivation kinetics. This effect on evoked NMDA currents was reproduced in WT neurons byindependent PrP-RNAi, NR2D-RNAi transfection, and eliminated by PrPCtransfection into PrP-null neurons. In addition, PrP coimmunoprecipitated with NR2D and not NR2B NMDA receptor subunits. In vitro and in vivo experiments utilizing transient exposure to NMDA showed greater cell death in PrP-nullneurons, which was significantly reduced by application of an NMDA receptor antagonist. Conclusions: These data suggest that enhanced NMDA activity is present in PrP-null neurons. Consistent with this finding, in vitro and in vivo excitotoxicity assays demonstrated increased neuronal cell death in PrP-null cultures and animals upon transient exposure to NMDA. This was confirmed at the level of synaptic currents showing prolonged receptor deactivation kinetics that were most consistent with functional activation of NR2D NMDA receptor subunits. Enhanced NMDA receptor function was paralleled by increased excitotoxicity in PrP-null mice. Our findings demonstrate a novel functional role for PrP as a modulator of synaptic NMDA currents and attributes a neuroprotective function to PrP.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

scholarly journals Plant-Derived Extracellular Vesicles: Current Findings,Challenges, and Future Applications

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 411
Author(s):  
Nader Kameli ◽  
Anya Dragojlovic-Kerkache ◽  
Paul Savelkoul ◽  
Frank R. Stassen
Keyword(s):  
Human Health ◽  
Extracellular Vesicles ◽  
Preliminary Results ◽  
In Vivo Experiments ◽  
Health And Disease ◽  
Conducting Research ◽  
Protocol Standardization ◽  
Insight Into

In recent years, plant-derived extracellular vesicles (PDEVs) have gained the interest of many experts in fields such as microbiology and immunology, and research in this field has exponentially increased. These nano-sized particles have provided researchers with a number of interesting findings, making their application in human health and disease very promising. Both in vitro and in vivo experiments have shown that PDEVs can exhibit a multitude of effects, suggesting that these vesicles may have many potential future applications, including therapeutics and nano-delivery of compounds. While the preliminary results are promising, there are still some challenges to face, such as a lack of protocol standardization, as well as knowledge gaps that need to be filled. This review aims to discuss various aspects of PDEV knowledge, including their preliminary findings, challenges, and future uses, giving insight into the complexity of conducting research in this field.

scholarly journals Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice

2020 ◽  
Vol 22 (1) ◽  
pp. 233
Author(s):  
Eunkuk Park ◽  
Chang Gun Lee ◽  
Eunguk Lim ◽  
Seokjin Hwang ◽  
Seung Hee Yun ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Osteoblastic Differentiation ◽  
Common Disease ◽  
Root Extract ◽  
Mouse Bone Marrow ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
In Vivo Experiments

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.

scholarly journals Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1985
Author(s):  
Xiaohe Li ◽  
Ling Ma ◽  
Kai Huang ◽  
Yuli Wei ◽  
Shida Long ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
In Vivo Experiments ◽  
Age Related ◽  
And Migration ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

scholarly journals Bioactive Compounds from Herbal Medicine Targeting Multiple Myeloma

2021 ◽  
Vol 11 (10) ◽  
pp. 4451
Author(s):  
Coralia Cotoraci ◽  
Alina Ciceu ◽  
Alciona Sasu ◽  
Eftimie Miutescu ◽  
Anca Hermenean
Keyword(s):  
Multiple Myeloma ◽  
Survival Rate ◽  
Plasma Cells ◽  
Inhibition Of Proliferation ◽  
In Vivo Experiments ◽  
Clonal Proliferation ◽  
Hematological Cancers ◽  
Monoclonal Proteins

Multiple myeloma (MM) is one of the most widespread hematological cancers. It is characterized by a clonal proliferation of malignant plasma cells in the bone marrow and by the overproduction of monoclonal proteins. In recent years, the survival rate of patients with multiple myeloma has increased significantly due to the use of transplanted stem cells and of the new therapeutic agents that have significantly increased the survival rate, but it still cannot be completely cured and therefore the development of new therapeutic products is needed. Moreover, many patients have various side effects and face the development of drug resistance to current therapies. The purpose of this review is to highlight the bioactive active compounds (flavonoids) and herbal extracts which target dysregulated signaling pathway in MM, assessed by in vitro and in vivo experiments or clinical studies, in order to explore their healing potential targeting multiple myeloma. Mechanistically, they demonstrated the ability to promote cell cycle blockage and apoptosis or autophagy in cancer cells, as well as inhibition of proliferation/migration/tumor progression, inhibition of angiogenesis in the tumor vascular network. Current research provides valuable new information about the ability of flavonoids to enhance the apoptotic effects of antineoplastic drugs, thus providing viable therapeutic options based on combining conventional and non-conventional therapies in MM therapeutic protocols.

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