Interactions between network synchrony and the dynamics of neuronal threshold

2012 ◽  
Vol 107 (11) ◽  
pp. 2926-2936 ◽  
Author(s):  
Avner Wallach ◽  
Shimon Marom
Keyword(s):  
Single Neuron ◽  
Cellular Level ◽  
Network Activity ◽  
Threshold Dynamics ◽  
Synchronous Activity ◽  
Interactive Nature ◽  
Synchronous Network ◽  
Health And Disease ◽  
The Impact

Synchronous activity impacts on a range of functional brain capacities in health and disease. To address the interrelations between cellular level activity and network-wide synchronous events, we implemented in vitro a recently introduced technique, the response clamp, which enables online monitoring of single neuron threshold dynamics while ongoing network synchronous activity continues uninterrupted. We show that the occurrence of a synchronous network event causes a significant biphasic change in the single neuron threshold. These threshold dynamics are correlated across the neurons constituting the network and are entailed by the input to the neurons rather than by their own spiking (i.e., output) activity. The magnitude of network activity during a synchronous event is correlated with the threshold state of individual neurons at the event's onset. Recovery from the impact of a given synchronous event on the neuronal threshold lasts several seconds and seems to be a key determinant of the time to the next spontaneously occurring synchronous event. Moreover, the neuronal threshold is shown to be correlated with the excitability dynamics of the entire network. We conclude that the relations between the two levels (network activity and the single neuron threshold) should be thought of in terms that emphasize their interactive nature.

Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1394-1407 ◽  
Author(s):  
Sarah Potez ◽  
Matthew E. Larkum
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Animal Experiments ◽  
Apical Dendrite ◽  
Network Activity ◽  
Calcium Spikes ◽  
Firing Properties ◽  
The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

scholarly journals Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1806 ◽  
Author(s):  
Eirini Dimidi ◽  
Selina Rose Cox ◽  
Megan Rossi ◽  
Kevin Whelan
Keyword(s):  
Controlled Trial ◽  
Health Benefits ◽  
Biologically Active ◽  
Fermented Foods ◽  
Lactose Malabsorption ◽  
Gastrointestinal Health ◽  
Sourdough Bread ◽  
Health And Disease ◽  
The Impact

Fermented foods are defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. In recent years, fermented foods have undergone a surge in popularity, mainly due to their proposed health benefits. The aim of this review is to define and characterise common fermented foods (kefir, kombucha, sauerkraut, tempeh, natto, miso, kimchi, sourdough bread), their mechanisms of action (including impact on the microbiota), and the evidence for effects on gastrointestinal health and disease in humans. Putative mechanisms for the impact of fermented foods on health include the potential probiotic effect of their constituent microorganisms, the fermentation-derived production of bioactive peptides, biogenic amines, and conversion of phenolic compounds to biologically active compounds, as well as the reduction of anti-nutrients. Fermented foods that have been tested in at least one randomised controlled trial (RCT) for their gastrointestinal effects were kefir, sauerkraut, natto, and sourdough bread. Despite extensive in vitro studies, there are no RCTs investigating the impact of kombucha, miso, kimchi or tempeh in gastrointestinal health. The most widely investigated fermented food is kefir, with evidence from at least one RCT suggesting beneficial effects in both lactose malabsorption and Helicobacter pylori eradication. In summary, there is very limited clinical evidence for the effectiveness of most fermented foods in gastrointestinal health and disease. Given the convincing in vitro findings, clinical high-quality trials investigating the health benefits of fermented foods are warranted.

scholarly journals Neuromodulation of astrocytic K+ clearance

2019 ◽  
Author(s):  
Alba Bellot-Saez ◽  
Orsolya Kékesi ◽  
Yuval Ben-Abu ◽  
John W. Morley ◽  
Yossi Buskila
Keyword(s):  
Network Activity ◽  
Oscillatory Behaviour ◽  
Kir Channels ◽  
Neuronal Network Activity ◽  
Synergistic Mechanism ◽  
Synchronous Network ◽  
Clearance Process ◽  
Spatial Buffering ◽  
Parallel Activation ◽  
The Impact

ABSTRACTPotassium homeostasis is a fundamental requirement for normal brain function. Therefore, effective removal of excessive K+ accumulation from the synaptic cleft during neuronal activity is paramount. Astrocytes, one of the most common subtype of glial cells in the brain, play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]°) or impairments of the astrocytic clearance mechanism effect the resonance and oscillatory behaviour of both individual and networks of neurons recorded from C57/BL6 mice of both sexes. These results indicate that astrocytes have the potential to modulate neuronal network activity, however the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behaviour, on the astrocytic clearance process. Our results suggest that some neuromodulators (5-HT; NA) affect astrocytic spatial buffering via gap-junctions, while others (DA; Histamine) affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to recruitment of neurons into ensamble of networks to maximise the synchronous network activity.Significance statementNeuromodulators are known to mediate changes in network oscillatory behaviour and thus impact on brain states. In this study we show that certain neuromodulators directly affect distinct stages of astrocytic K+ clearance, promoting neuronal excitability and network oscillations through parallel activation of both neurons and astrocytes, thus establishing a synergistic mechanism to maximise the synchronous network activity.

scholarly journals Single-Neuron Discharge Properties and Network Activity in Dissociated Cultures of Neocortex

2004 ◽  
Vol 92 (2) ◽  
pp. 977-996 ◽  
Author(s):  
M. Giugliano ◽  
P. Darbon ◽  
M. Arsiero ◽  
H.-R. Lüscher ◽  
J. Streit
Keyword(s):  
Single Cell ◽  
Single Neuron ◽  
Neuronal Response ◽  
Mean Field ◽  
Network Activity ◽  
Model Parameters ◽  
Cell Discharge ◽  
Collective Activity ◽  
The Mean

Cultures of neurons from rat neocortex exhibit spontaneous, temporally patterned, network activity. Such a distributed activity in vitro constitutes a possible framework for combining theoretical and experimental approaches, linking the single-neuron discharge properties to network phenomena. In this work, we addressed the issue of closing the loop, from the identification of the single-cell discharge properties to the prediction of collective network phenomena. Thus, we compared these predictions with the spontaneously emerging network activity in vitro, detected by substrate arrays of microelectrodes. Therefore, we characterized the single-cell discharge properties to Gauss-distributed noisy currents, under pharmacological blockade of the synaptic transmission. Such stochastic currents emulate a realistic input from the network. The mean ( m) and variance ( s2) of the injected current were varied independently, reminiscent of the extended mean-field description of a variety of possible presynaptic network organizations and mean activity levels, and the neuronal response was evaluated in terms of the steady-state mean firing rate ( f). Experimental current-to-spike–rate responses f( m, s2) were similar to those of neurons in brain slices, and could be quantitatively described by leaky integrate-and-fire (IF) point neurons. The identified model parameters were then used in numerical simulations of a network of IF neurons. Such a network reproduced a collective activity, matching the spontaneous irregular population bursting, observed in cultured networks. We finally interpret such a collective activity and its link with model details by the mean-field theory. We conclude that the IF model is an adequate minimal description of synaptic integration and neuronal excitability, when collective network activities are considered in vitro.

scholarly journals Limited Hydrolysis of Polysialic Acid by Human Neuraminidase Enzymes

2021 ◽  
Author(s):  
Carmanah D. Hunter ◽  
Christopher Cairo
Keyword(s):  
Polysialic Acid ◽  
Chemical Properties ◽  
Sialic Acids ◽  
Degree Of Polymerization ◽  
Health And Disease ◽  
Substrate Tolerance ◽  
The Impact ◽  
Hydrolysis Of ◽  
Unique Chemical

Regulation of sialic acids by human neuraminidase (hNEU) enzymes is important to many biological processes. Defining hNEU substrate tolerance can help to elucidate the roles of these enzymes in regulating sialosides in human health and disease. Polysialic acid (polySia) is a polyanion of α(2→8) linked sialic acids with roles in nervous, reproductive, and immune systems and is dysregulated in some malignancies and mental disorders. The unique chemical properties of this polymer, which include an enhanced susceptibility to acid-catalyzed hydrolysis, have hampered its study. Herein we describe the first<i> </i>systematic study of hNEU isoenzyme activity towards polysialic acid <i>in vitro.</i> The experimental design allowed us to study the impact of several factors that may influence polysialic acid degradation including pH, polymer size, and the relative ionic strength of the surrounding media. We report that short chains of polysialic acid (degree of polymerization, DP 3-8) were substrates of NEU3 and NEU4 at acidic pH, but not at neutral pH. No hNEU-catalyzed hydrolysis of longer polymers (DP 10-20) was detected. These findings suggest a neuraminidase-independent mechanism for polysialic acid turnover such as internalization and degradation in endosomes and lysosomes.

scholarly journals Allele-specific expression reveals interactions between genetic variation and environment

2015 ◽  
Author(s):  
David A Knowles ◽  
Joe R Davis ◽  
Anil Raj ◽  
Xiaowei Zhu ◽  
James B Potash ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Cellular Level ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Sequencing Studies ◽  
Allele Specific ◽  
Gxe Interactions ◽  
Over Dispersion ◽  
The Impact

The impact of environment on human health is dramatic, with major risk factors including substance use, diet and exercise. However, identifying interactions between the environment and an individual's genetic background (GxE) has been hampered by statistical and computational challenges. By combining RNA sequencing of whole blood and extensive environmental annotations collected from 922 individuals, we have evaluated GxE interactions at a cellular level. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on association between environment and allele-specific expression (ASE). EAGLE increases power by leveraging the controlled, within-sample comparison of environmental impact on different genetic backgrounds provided by ASE, while also taking into account technical covariates and over-dispersion of sequencing read counts. EAGLE identifies 35 GxE interactions, a substantial increase over standard GxE testing. Among EAGLE hits are variants that modulate response to smoking, exercise and blood pressure medication. Further, application of EAGLE identifies GxE interactions to infection response that replicate results reported in vitro, demonstrating the power of EAGLE to accurately identify GxE candidates from large RNA sequencing studies.

scholarly journals The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease

2018 ◽  
Vol 19 (11) ◽  
pp. 3425 ◽  
Author(s):  
Céline Tiffon
Keyword(s):  
Environmental Factors ◽  
Human Health ◽  
Disease Risk ◽  
Cellular Level ◽  
Epigenetic Modifications ◽  
Environmental Signals ◽  
Environmental Epigenetics ◽  
Health And Disease ◽  
Potential Strategy ◽  
The Impact

Environmental epigenetics describes how environmental factors affect cellular epigenetics and, hence, human health. Epigenetic marks alter the spatial conformation of chromatin to regulate gene expression. Environmental factors with epigenetic effects include behaviors, nutrition, and chemicals and industrial pollutants. Epigenetic mechanisms are also implicated during development in utero and at the cellular level, so environmental exposures may harm the fetus by impairing the epigenome of the developing organism to modify disease risk later in life. By contrast, bioactive food components may trigger protective epigenetic modifications throughout life, with early life nutrition being particularly important. Beyond their genetics, the overall health status of an individual may be regarded as an integration of many environmental signals starting at gestation and acting through epigenetic modifications. This review explores how the environment affects the epigenome in health and disease, with a particular focus on cancer. Understanding the molecular effects of behavior, nutrients, and pollutants might be relevant for developing preventative strategies and personalized heath programs. Furthermore, by restoring cellular differentiation, epigenetic drugs could represent a potential strategy for the treatment of many diseases including cancer.

scholarly journals Potential of zebrafish as a model to characterise MicroRNA profiles in mechanically mediated joint degeneration

2020 ◽  
Author(s):  
Elizabeth A. Lawrence ◽  
Chrissy L. Hammond ◽  
Emma J. Blain
Keyword(s):  
Mechanical Load ◽  
Disease Onset ◽  
Cellular Level ◽  
Joint Degeneration ◽  
In Vivo Models ◽  
Joint Health ◽  
Transgenic Lines ◽  
Health And Disease

Abstract Mechanically mediated joint degeneration and cartilage dyshomeostasis is implicated in highly prevalent diseases such as osteoarthritis. Increasingly, MicroRNAs are being associated with maintaining the normal state of cartilage, making them an exciting and potentially key contributor to joint health and disease onset. Here, we present a summary of current in vitro and in vivo models which can be used to study the role of mechanical load and MicroRNAs in joint degeneration, including: non-invasive murine models of PTOA, surgical models which involve ligament transection, and unloading models based around immobilisation of joints or removal of load from the joint through suspension. We also discuss how zebrafish could be used to advance this field, namely through the availability of transgenic lines relevant to cartilage homeostasis and the ability to accurately map strain through the cartilage, enabling the response of downstream MicroRNA targets to be followed dynamically at a cellular level in areas of high and low strain.

scholarly journals Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1564
Author(s):  
Federica Lamberto ◽  
Irene Peral-Sanchez ◽  
Suchitra Muenthaisong ◽  
Melinda Zana ◽  
Sandrine Willaime-Morawek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cardiovascular Diseases ◽  
Embryonic Development ◽  
Pluripotent Stem Cells ◽  
Developmental Origins ◽  
Maternal Factors ◽  
Health And Disease ◽  
Induced Pluripotent ◽  
The Impact

Non-communicable diseases (NCDs) sauch as diabetes, obesity and cardiovascular diseases are rising rapidly in all countries world-wide. Environmental maternal factors (e.g., diet, oxidative stress, drugs and many others), maternal illnesses and other stressors can predispose the newborn to develop diseases during different stages of life. The connection between environmental factors and NCDs was formulated by David Barker and colleagues as the Developmental Origins of Health and Disease (DOHaD) hypothesis. In this review, we describe the DOHaD concept and the effects of several environmental stressors on the health of the progeny, providing both animal and human evidence. We focus on cardiovascular diseases which represent the leading cause of death worldwide. The purpose of this review is to discuss how in vitro studies with pluripotent stem cells (PSCs), such as embryonic and induced pluripotent stem cells (ESC, iPSC), can underpin the research on non-genetic heart conditions. The PSCs could provide a tool to recapitulate aspects of embryonic development “in a dish”, studying the effects of environmental exposure during cardiomyocyte (CM) differentiation and maturation, establishing a link to molecular mechanism and epigenetics.

Spontaneous Development of Synchronous Oscillatory Activity During Maturation of Cortical Networks In Vitro

2002 ◽  
Vol 88 (5) ◽  
pp. 2196-2206 ◽  
Author(s):  
Thoralf Opitz ◽  
Ana D. De Lima ◽  
Thomas Voigt
Keyword(s):  
Large Scale ◽  
Reversal Potential ◽  
Neuronal Population ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Pharmacological Intervention ◽  
Resting Membrane Potential ◽  
Cortical Networks ◽  
Synchronous Network

Recent studies have focused attention on mechanisms of spontaneous large-scale wavelike activity during early development of the neocortex. In this study, we describe and characterize synchronous neuronal activity that occurs in cultured cortical networks naturally without pharmacological intervention. The synchronous activity that can be detected by means of Fluo-3 fluorescence imaging starts to develop at the beginning of the second week in culture and eventually includes the entire neuronal population about 1 wk later. A synchronous increase of [Ca2+]i in the neuronal population is associated with a burst of action potentials riding on a long-lasting depolarization recorded in a single cell. It is suggested that this depolarization results directly from synaptic current, which was comprised of at least three different components mediated by AMPA, N-methyl-d-aspartate (NMDA), and GABAA receptors. We never observed a gradually depolarizing pacemaker potential and found no evidence for a change of excitability during inter-burst periods. However, we found evidence for a period of synaptic depression after bursts. Network excitability recovers gradually over seconds from this depression that can explain the episodic nature of spontaneous network activity. Using pharmacological manipulation to investigate the propagation of activity in the network, we show that synchronous network activity depends on both glutamatergic and GABAAergic neurotransmission during a brief period. Reversal potential of GABAA receptor-mediated current was found to be significantly more positive than resting membrane potential both at 1 and 2 wk in culture, suggesting depolarizing action of GABA. However, in cultures older than 2 wk, inhibition of GABAAreceptors does not result in block of synchronous network activity but in modulation of burst width and frequency.

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