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 A MICROCALORIMETRIC STUDY OF TURTLE CORTICAL SLICES: INSIGHTS INTO BRAIN METABOLIC DEPRESSION

1994 ◽  
Vol 191 (1) ◽  
pp. 141-153 ◽  
Author(s):  
C Doll ◽  
P Hochachka ◽  
S Hand
Keyword(s):  
Cortical Neurons ◽  
Heat Dissipation ◽  
Energy Charge ◽  
Utilization Rate ◽  
Rapid Decline ◽  
Metabolic Depression ◽  
Slice Preparation ◽  
Cortical Slices

In previous papers, we have examined turtle cortical neurons in vitro for mechanisms of anoxic metabolic depression ('channel arrest' and changes in electrical parameters). Negative results prompted the current study with the aim of examining more closely the energy profile and metabolism of turtle cortical slices. Calorimetry is used to measure heat dissipation during normoxia and nitrogen perfusion (120 min) and the results are converted into an ATP utilization rate. These indicate that the control rate of ATP utilization (1.72 µmol ATP g-1 min-1) agrees closely with in vivo whole-brain metabolic measurements. Both nitrogen perfusion and pharmacologically induced anoxic (cyanide+N2) groups depressed heat dissipation considerably compared with the control value (nitrogen 37 %; pharmacological anoxia 49 %). The resulting ATP utilization estimates indicate metabolic depressions of 30 % (nitrogen) and 42 % (pharmacological anoxia). The slice preparation did not exhibit a change in any measured adenylate parameter for up to 120 min of anoxia or pharmacological anoxia. Significant changes did occur in [ADP], ATP/ADP ratio and energy charge after 240 min of exposure to anoxic conditions. These results support the idea that the turtle cortical slice preparation has a profound resistance to anoxia, with both nitrogen perfusion and pharmacological anoxia causing a rapid decline in heat dissipation and metabolism.

scholarly journals 0017 Transmembrane TNF- Soluble TNF Receptor Reverse Signal to Induce a Wake-Like State in Vitro

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A7-A7
Author(s):  
C J Dykstra-Aiello ◽  
K Koh ◽  
J Nguyen ◽  
J M Krueger
Keyword(s):  
Cortical Neurons ◽  
Action Potentials ◽  
State Regulation ◽  
Electrode Arrays ◽  
Electrophysiological Properties ◽  
Reverse Signaling ◽  
Soluble Tnf Receptor ◽  
Induced Changes

Abstract Introduction Tumor necrosis factor (TNF) has sleep regulatory roles. Neuronal action potentials enhance TNF expression. Neuron/glia co-cultures exhibit more intense local sleep-like states after TNF administration in vitro. Both TNF and TNF receptors (Rs) are produced as transmembrane (tm) proteins that can subsequently be cleaved to produce soluble (s) forms. With immunocytes, sTNFR can bind tmTNF and induce reverse signaling within the cell expressing the tmTNF. This is opposite of conventional signaling induced by soluble ligands (e.g. sTNF) binding to transmembrane receptors. Having previously shown sleep inhibition after sTNFR administration in vivo, we hypothesized that tmTNF-sTNFR binding would induce wake-like states in vitro through reverse signaling. Methods Somatosensory cortical neurons/glia, from wildtype (WT) mice and mice lacking either TNF (TNF-KO) or both TNFRs (TNFR-KO), were co-cultured on multi-electrode arrays. Daily one-hour recordings were taken consecutively on incubation days 4 - 13 for development analyses. On day 14, a one-hour baseline was recorded prior to treatment with sTNFR (0.0 ng/μL-120 ng/μL). Immediately after treatment, recordings resumed for one hour. Synchronization of electrical activity (SYN), action potentials, slow wave power (SWP; 0.25–3.75 Hz), and burstiness index (measures used to define sleep in vivo) were used to characterize the ontological emergence of these electrophysiological properties and sTNFR-induced changes in vitro. Results Development rates were reduced in TNF-KO cells and increased in TNFR-KO cells relative to each other and to WT mice. Additionally, after sTNFR treatments, cells from TNFR-KO mice, which still express TNF, exhibited dose-dependent decreased SYN and SWP, indicative of a wake-like state. In contrast, cells from TNF-KO mice lacked a response to sTNFR treatment. Conclusion To our knowledge, this is the first demonstration of reverse TNF signaling with respect to sleep/wake states. As such, it provides a new way of viewing state regulation and associated potential clinical applications. Support This work was supported by grant NS096250 awarded to JK by NIH/NINDS.

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 An Open-Source Wireless Electrophysiological Complex for In Vivo Recording Neuronal Activity in the Rodent’s Brain

Sensors ◽  
2021 ◽  
Vol 21 (21) ◽  
pp. 7189
Author(s):  
Alexander Erofeev ◽  
Dmitriy Kazakov ◽  
Nikita Makarevich ◽  
Anastasia Bolshakova ◽  
Evgenii Gerasimov ◽  
...  
Keyword(s):  
Open Source ◽  
Neuronal Activity ◽  
Ex Vivo ◽  
Electrode Arrays ◽  
Charging Station ◽  
In Vivo Experiments ◽  
The Brain ◽  
Schematic Diagrams

Multi-electrode arrays (MEAs) are a widely used tool for recording neuronal activity both in vitro/ex vivo and in vivo experiments. In the last decade, researchers have increasingly used MEAs on rodents in vivo. To increase the availability and usability of MEAs, we have created an open-source wireless electrophysiological complex. The complex is scalable, recording the activity of neurons in the brain of rodents during their behavior. Schematic diagrams and a list of necessary components for the fabrication of a wireless electrophysiological complex, consisting of a base charging station and wireless wearable modules, are presented.

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 TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhou ◽  
Tao Tao ◽  
Guangjie Liu ◽  
Xuan Gao ◽  
Yongyue Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

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