Burst Dynamics Research Articles

Robust bursting dynamics based on the interaction of persistent Na and Na/K pump currents: a dynamic clamp approach.

Life-supporting rhythmic motor functions like heart-beating in invertebrates and breathing in vertebrates require an indefatigable generation of a robust rhythm by specialized oscillatory circuits, Central Pattern Generators (CPGs). These CPGs should be sufficiently flexible to adjust to environmental changes and behavioral goals. Continuous self-sustained operation of bursting neurons requires intracellular Na+ concentration to remain in a functional range and to have checks and balances of the Na+ fluxes met on a cycle-to-cycle basis during bursting. We hypothesize that at a high excitability state, the interaction of the Na+/K+ pump current, Ipump and persistent Na+ current, INaP, produces a mechanism supporting functional bursting. INaP is a low voltage-activated inward current that initiates and supports the bursting phase. This current does not inactivate and is a significant source of Na+ influx. Ipump is an outward current activated by [Na+]i and is the major source of Na+ efflux. Both currents are active and counteract each other between and during bursts. We apply a combination of electrophysiology, computational modeling, and dynamic clamp to investigate the role of Ipump and INaP in the leech heartbeat CPG interneurons (HN neurons). Applying dynamic clamp to introduce additional Ipump and INaP into the dynamics of living synaptically isolated HN neurons in real-time, we show that their joint increase produces transition into a new bursting regime characterized by higher spike frequency and larger amplitude of the membrane potential oscillations. Further increase of Ipump speeds up this rhythm by shortening burst duration and interburst interval.Significance statementCentral Pattern Generators (CPGs) are neuronal networks that control rhythmic motor functions such as breathing and walking. Synaptic and membrane properties enable participating neurons to generate functional bursting patterns; intracellular Na+ concentration reflects the intensity of the spiking activity during bursts and regulates the Na+/K+ pump current playing a critical role in sculpting these patterns by providing negative feedback in response to excitation. Here, we show that the dynamic interaction of Na+/K+ pump current with persistent Na+ current offers a mechanism for the generation of a robust and flexible pattern of bursting activity. We provide physiological data and present a simple model that explains the underlying dynamics of the oscillatory mechanism.

A behavioral and modeling study of control algorithms underlying the translational optomotor response in larval zebrafish with implications for neural circuit function.

The optomotor response (OMR) is central to the locomotory behavior in diverse animal species including insects, fish and mammals. Furthermore, the study of the OMR in larval zebrafish has become a key model system for investigating the neural basis of sensorimotor control. However, a comprehensive understanding of the underlying control algorithms is still outstanding. In fish it is often assumed that the OMR, by reducing average optic flow across the retina, serves to stabilize position with respect to the ground. Yet the degree to which this is achieved, and how it could emerge from the intermittent burst dynamics of larval zebrafish swimming, are unclear. Here, we combine detailed computational modeling with a new approach to free-swimming experiments in which we control the amount of visual feedback produced by a given motor effort by varying the height of the larva above a moving grid stimulus. We develop an account of underlying feedback control mechanisms that describes both the bout initiation process and the control of swim speed during bouts. We observe that the degree to which fish stabilize their position is only partial and height-dependent, raising questions about its function. We find the relative speed profile during bouts follows a fixed temporal pattern independent of absolute bout speed, suggesting that bout speed and bout termination are not separately controlled. We also find that the reverse optic flow, experienced when the fish is swimming faster than the stimulus, plays a minimal role in control of the OMR despite carrying most of the sensory information about self-movement. These results shed new light on the underlying dynamics of the OMR in larval zebrafish and will be crucial for future work aimed at identifying the neural basis of this behavior.

Selective inhibition of excitatory synaptic transmission alters the emergent bursting dynamics of in vitro neural networks.

Neurons in vitro connect to each other and form neural networks that display emergent electrophysiological activity. This activity begins as spontaneous uncorrelated firing in the early phase of development, and as functional excitatory and inhibitory synapses mature, the activity typically emerges as spontaneous network bursts. Network bursts are events of coordinated global activation among many neurons interspersed with periods of silencing and are important for synaptic plasticity, neural information processing, and network computation. While bursting is the consequence of balanced excitatory-inhibitory (E/I) interactions, the functional mechanisms underlying their evolution from physiological to potentially pathophysiological states, such as decreasing or increasing in synchrony, are still poorly understood. Synaptic activity, especially that related to maturity of E/I synaptic transmission, is known to strongly influence these processes. In this study, we used selective chemogenetic inhibition to target and disrupt excitatory synaptic transmission in in vitro neural networks to study functional response and recovery of spontaneous network bursts over time. We found that over time, inhibition resulted in increases in both network burstiness and synchrony. Our results indicate that the disruption in excitatory synaptic transmission during early network development likely affected inhibitory synaptic maturity which resulted in an overall decrease in network inhibition at later stages. These findings lend support to the importance of E/I balance in maintaining physiological bursting dynamics and, conceivably, information processing capacity in neural networks.

Rules of transcriptional bursting revealed by absolute quantification of nascent RNA in living fly embryos.

Transcriptional bursting is a common regulatory strategy for controlling gene outputs in various organisms. Over the past 15 years, experiments that dissected transcriptional regulation into its smaller parts have helped us identify many molecular processes associated with burst modulation under various physiological conditions, such as enhancer regulation, transcription factor regulation, epigenetics modifications, etc. However, these reductionist insights have not yet been successful in adding up to a coherent biophysical model that links molecular mechanisms to empirical bursting dynamics. In this work, we provide a unified perspective on this problem by quantifying transcriptional activity in live Drosophila embryos with single RNA detection sensitivity. We reveal a common regulatory strategy that displays surprising constraints on transcriptional bursting under a whole variety of different experimental conditions, including cis- and trans-perturbations in mutant fly strains. We observe a massive data collapse across all conditions, hinting at general rules underlying the dynamics of transcriptional bursting that could be linked to evolutionarily conserved biophysical properties of the core eukaryotic transcriptional machinery.

Flame dynamics of hydrogen/air mixture in a wavy micro-channel

The focus of this work is the numerical study of stable and pulsatory flame burst in an undulating geometry, using premixed hydrogen and air (with an equivalence ratio of φ = 1.0). This work extends other works in the literature by considering a linear temperature profile along the wall. This allows an analysis of the flow dynamics without forcing the location of the flame (as is the case with hyperbolic temperature profiles). The interaction between the flow dynamics and the combustion reaction is then analysed, leading to a better understanding of the physics in more general flows.Simulations were performed in OpenFoam using very detailed chemical reactions and different molecular diffusivities for each species. The results obtained show that at low inlet velocity (4 m/s) the flame became stable, and, at higher inlet velocities, the flame showed pulsatory burst dynamics. The interaction between the fluid dynamics and the combustion response proved to be important, especially because of the vortices that are formed due to the nonlinear geometry of the burner. As the inlet velocity increases, the heat release rate transmitted through the vortices decreases and a delay in ignition occurs, as evidenced by a decrease in the pulsatory burst frequency and an increase in the maximum value of the heat release rate (although not sufficient to increase the maximum temperature amplitude).In addition, we also carried out an analyses of the axial velocity and of the H2 and OH mass fractions of the flame dynamics.

A comparison of methods to suppress electrocardiographic artifacts in local field potential recordings

ObjectiveLocal field potential (LFP) recordings from deep brain stimulation (DBS) electrodes are often contaminated with electrocardiographic (ECG) artifacts that hinder the detection of disease-specific electrical brain activity. MethodsThree ECG suppression methods were evaluated: (1) QRS interpolation of the Perceive toolbox, (2) template subtraction, and (3) singular value decomposition (SVD). LFPs were recorded with the Medtronic PerceptTM PC system in nine Parkinson’s disease patients with stimulation OFF (“OFF-DBS”; anode disconnected) and ON at 0 mA (“ON-DBS 0 mA”; anode connected). Findings were verified with simulated ECG-contaminated time series. ResultsECG artifacts were present in 10 out of 18 ON-DBS 0 mA recordings. All ECG suppression methods drastically reduced artifact-induced beta band (13–35 Hz) power and at least partly recovered the beta peak and beta burst dynamics. Using external ECG recordings and lengthening artifact epoch length improved the performance of the suppression methods. Increasing epoch length, however, elevated the risk of flattening the beta peak and losing beta burst dynamics. ConclusionsThe SVD method formed the preferred trade-off between artifact cleaning and signal loss, as long as its parameter settings are adequately chosen. SignificanceECG suppression methods enable analysis of disease-specific neural activity from signals affected by ECG artifacts.

On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation

Determining the mechanisms by which genes are switched on and off during development is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using an on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in transcriptional activity whereas at the peak of gene expression, in early erythroblasts, transcription is relatively stable. Later during differentiation as α-globin expression declines, we again observe more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of active transcriptional compartments as gene expression is regulated during differentiation.

Study on deformations of gold film induced by ultrafast laser at GHz burst mode

Deformation structure is very common in ultrafast laser processing metal film, but it is undesirable in some application scenarios. In this study, ultrafast laser at burst mode is used to suppress the deformation of metal film induced by ultrafast laser. The experimental research of 40 nm gold film irradiated by ultrafast laser at GHz burst mode has been carried out, with different numbers of sub-pulses from 1 to 25. When the burst fluence is lower than the ablation threshold, the height of bump decreases with the number of sub-pulses increasing in the burst and Molecular Dynamics (MD) simulations are carried out to explore the mechanism of deformation behaviors. While the burst fluence is higher than the ablation threshold, the deformation behaviors around the ablation hole also change interestingly with different number of sub-pulses, which can be divided into three stages. The increase of width of burrs, the decrease of driving force and the molten film left at edge of ablation hole, induced by the number of sub-pulses increasing, cause different deformation behaviors of gold film, respectively.

Supercoiling-mediated feedback rapidly couples and tunes transcription.

Transcription induces a wave of DNA supercoiling, altering the binding affinity of RNA polymerases and reshaping the biochemical landscape of gene regulation. As supercoiling rapidly diffuses, transcription dynamically reshapes the regulation of proximal genes, forming a complex feedback loop. However, a theoretical framework is needed to integrate biophysical regulation with biochemical transcriptional regulation. To investigate the role of supercoiling-mediated feedback within multi-gene systems, we model transcriptional regulation under the influence of supercoiling-mediated polymerase dynamics, allowing us to identify patterns of expression that result from physical inter-gene coupling. We find that gene syntax-the relative ordering and orientation of genes-defines the expression profiles, variance, burst dynamics, and inter-gene correlation of two-gene systems. Furthermore, supercoiling can enhance or weaken biochemical regulation. Our results suggest that supercoiling couples behavior between neighboring genes, providing a regulatory mechanism that tunes transcriptional variance in engineered gene networks and explains the behavior of co-localized native circuits.

Credit allocation and the financial crisis: evidence from Spanish companies

The worldwide financial crisis of 2007–2008 raised serious concerns about the soundness of banks’ activities and about the extent to which banking regulation should supervise banks’ investment decisions. We contribute to this topic by examining the Spanish case, which has been emblematic of the bubble and burst dynamics in the credit market. In particular, we study the allocation of bank credit among Spanish companies from 1999 to 2014, showing that larger companies accumulated greater amounts of bank loans per unit of total assets, thus leading to a notable concentration. We also find that, during the Spanish boom period, bank loans shifted from the manufacturing to the construction industry, and in particular to the largest companies of the latter sector. This happened in spite of the high leverage of large construction firms, which was increasing also due to their growing debt. We argue that the higher operating benefits, reflecting the increase of the housing price during the boom period, overvalued construction firms as potential borrowers. The bankruptcy of several large construction companies during the Spanish crisis supports the need for monitoring and regulation, to avoid an excessive concentration of bank credit to a few large companies, especially if they belong to a specific sector.

Novel bursting dynamics and the mechanism analysis in a mechanical oscillator

Novel bursting dynamics and the mechanism analysis in a mechanical oscillator

Cortical beta burst dynamics are altered in Parkinson's disease but normalized by deep brain stimulation

Exaggerated subthalamic beta oscillatory activity and increased beta range cortico-subthalamic synchrony have crystallized as the electrophysiological hallmarks of Parkinson's disease. Beta oscillatory activity is not tonic but occurs in ‘bursts’ of transient amplitude increases. In Parkinson's disease, the characteristics of these bursts are altered especially in the basal ganglia. However, beta oscillatory dynamics at the cortical level and how they compare with healthy brain activity is less well studied. We used magnetoencephalography (MEG) to study sensorimotor cortical beta bursting and its modulation by subthalamic deep brain stimulation in Parkinson's disease patients and age-matched healthy controls. We show that the changes in beta bursting amplitude and duration typical of Parkinson's disease can also be observed in the sensorimotor cortex, and that they are modulated by chronic subthalamic deep brain stimulation, which, in turn, is reflected in improved motor function at the behavioural level. In addition to the changes in individual beta bursts, their timing relative to each other was altered in patients compared to controls: bursts were more clustered in untreated Parkinson's disease, occurring in ‘bursts of bursts’, and re-burst probability was higher for longer compared to shorter bursts. During active deep brain stimulation, the beta bursting in patients resembled healthy controls’ data. In summary, both individual bursts’ characteristics and burst patterning are affected in Parkinson's disease, and subthalamic deep brain stimulation normalizes some of these changes to resemble healthy controls’ beta bursting activity, suggesting a non-invasive biomarker for patient and treatment follow-up.

Self-organized neuronal subpopulations and network morphology underlying superbursts

Neural bursts are an important phenomenon that needs to be understood for their relevance to many different neurological diseases as well as neural computations. While there are different types of neuronal bursts, in this study we investigate the nature of population (as opposed to intrinsic cell-level) bursts, in particular, superbursts (SBs) that are a small (∼100 ms) packet of several population bursts (PBs). It has been suggested that neuronal PBs occur when there exists a delicate balance of system-wide excitation and inhibition and when recurrent excitation loops exist in the network. However, there has been no rigorous investigation on the relation between network morphology and (super)burst dynamics. Here we investigate the important issue based on a well-established Izhikevich network model of integrate-fire neurons. We have employed the overall conduction delay as our control parameter for tuning network morphology as well as its matching burst dynamics. Interestingly, we found that initially identical neurons self-organize to develop several distinct neuronal subpopulations, which are characterized by different spike firing patterns as well as local network properties. Moreover, a few different motifs of SB emerge according to a distinct mixture of neuronal subpopulations that, on average, fire at slightly different phases. Our analyses suggest that recurring motifs of different SBs reflect complex yet organized modular structures of different subpopulations.

MYC amplifies gene expression through global changes in transcription factor dynamics.

The MYC oncogene has been studied for decades, yet there is still intense debate over how this transcription factor controls gene expression. Here, we seek to answer these questions with an invivo readout of discrete events of gene expression in single cells. We engineered an optogenetic variant of MYC (Pi-MYC) and combined this tool with single-molecule RNA and protein imaging techniques to investigate the role of MYC in modulating transcriptional bursting and transcription factor binding dynamics in human cells. We find that the immediate consequence of MYC overexpression is an increase in the duration rather than in the frequency of bursts, a functional role that is different from the majority of human transcription factors. We further propose that the mechanism by which MYC exerts global effects on the active period of genes is by altering the binding dynamics of transcription factors involved in RNA polymerase II complex assembly and productive elongation.

Burst Dynamics, Upscaling and Dissipation of Slow Drainage in Porous Media

We present a theoretical and experimental investigation of drainage in porous media. The study is limited to stabilized fluid fronts at moderate injection rates, but it takes into account capillary, viscous, and gravitational forces. In the theoretical framework presented, the work applied on the system, the energy dissipation, the final saturation and the width of the stabilized fluid front can all be calculated if we know the dimensionless fluctuation number, the wetting properties, the surface tension between the fluids, the fractal dimensions of the invading structure and its boundary, and the exponent describing the divergence of the correlation length in percolation. Furthermore, our theoretical description explains how the Haines jumps’ local activity and dissipation relate to dissipation on larger scales.

Cortico-subcortical β burst dynamics underlying movement cancellation in humans.

Dominant neuroanatomical models hold that humans regulate their movements via loop-like cortico-subcortical networks, which include the subthalamic nucleus (STN), motor thalamus, and sensorimotor cortex (SMC). Inhibitory commands across these networks are purportedly sent via transient, burst-like signals in the β frequency (15-29 Hz). However, since human depth-recording studies are typically limited to one recording site, direct evidence for this proposition is hitherto lacking. Here, we present simultaneous multi-site recordings from SMC and either STN or motor thalamus in humans performing the stop-signal task. In line with their purported function as inhibitory signals, subcortical β-bursts were increased on successful stop-trials. STN bursts in particular were followed within 50 ms by increased β-bursting over SMC. Moreover, between-site comparisons (including in a patient with simultaneous recordings from SMC, thalamus, and STN) confirmed that β-bursts in STN temporally precede thalamic β-bursts. This highly unique set of recordings provides empirical evidence for the role of β-bursts in conveying inhibitory commands along long-proposed cortico-subcortical networks underlying movement regulation in humans.

Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.

Background: Resting state beta band (13–30 Hz) oscillations represent pathological neural activity in Parkinson’s disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states.Methods: Subthalamic (STN) and local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa® PC + S, Medtronic PLC.) in fourteen PD participants (six tremor-dominant and eight akinetic-rigid) off medication/off STN DBS during 30 s of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups.Results: Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group.Conclusion: The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.

Activation-Inhibition dynamics of the oscillatory bursts of the human EEG during resting state. The macroscopic temporal range of few seconds

The ubiquitous brain oscillations occur in bursts of oscillatory activity. The present report tries to define the statistical characteristics of electroencephalographical (EEG) bursts of oscillatory activity during resting state in humans to define (i) the statistical properties of amplitude and duration of oscillatory bursts, (ii) its possible correlation, (iii) its frequency content, and (iv) the presence or not of a fixed threshold to trigger an oscillatory burst. The open eyes EEG recordings of five subjects with no artifacts were selected from a sample of 40 subjects. The recordings were filtered in frequency ranges of 2 Hz wide from 1 to 99 Hz. The analytic Hilbert transform was computed to obtain the amplitude envelopes of oscillatory bursts. The criteria of thresholding and a minimum of three cycles to define an oscillatory burst were imposed. Amplitude and duration parameters were extracted and they showed durations between hundreds of milliseconds and a few seconds, and peak amplitudes showed a unimodal distribution. Both parameters were positively correlated and the oscillatory burst durations were explained by a linear model with the terms peak amplitude and peak amplitude of amplitude envelope time derivative. The frequency content of the amplitude envelope was contained in the 0–2 Hz range. The results suggest the presence of amplitude modulated continuous oscillations in the human EEG during the resting conditions in a broad frequency range, with durations in the range of few seconds and modulated positively by amplitude and negatively by the time derivative of the amplitude envelope suggesting activation-inhibition dynamics. This macroscopic oscillatory network behavior is less pronounced in the low-frequency range (1–3 Hz).

Analysis of cellular and synaptic mechanisms behind spontaneous cortical activity in vitro: Insights from optimization of spiking neuronal network models

Spontaneous network bursts, the intervals of intense network-wide activity interleaved with longer periods of sparse activity, are a hallmark phenomenon observed in cortical networks at postnatal developmental stages. Generation, propagation and termination of network bursts depend on a combination of synaptic, cellular and network mechanisms; however, the interplay between these mechanisms is not fully understood. We study this interplay in silico, using a new data-driven framework for generating spiking neuronal networks fitted to the microelectrode array recordings. We recorded the network bursting activity from rat postnatal cortical networks under several pharmacological conditions. In each condition, the function of specific excitatory and inhibitory synaptic receptors was reduced in order to examine their impact on global network dynamics. The obtained data was used to develop two complementary model fitting protocols for automatic model generation. These protocols allowed us to disentangle systematically the modeled cellular and synaptic mechanisms that affect the observed network bursts. We confirmed that the change in excitatory and inhibitory synaptic transmission in silico, consistent with pharmacological conditions, can account for the changes in network bursts relative to the control data. Reproducing the exact recorded network bursts statistics required adapting both the synaptic transmission and the cellular excitability separately for each pharmacological condition. Our results bring new understanding of the complex interplay between cellular, synaptic and network mechanisms supporting the burst dynamics. While here we focused on analysis of in vitro data, our approach can be applied ex vivo and in vivo given that the appropriate experimental data is available.

The Energy Spectra of Electron Microbursts Between 200 keV and 1 MeV

AbstractThis study investigates the energy spectrum of electron microbursts observed by the Focused Investigations of Relativistic Electron Burst Intensity, Range, and Dynamics II (FIREBIRD‐II, henceforth FIREBIRD) CubeSats. FIREBIRD is a pair of CubeSats, launched in January 2015 into a low Earth orbit, which focuses on studying electron microbursts. High‐resolution electron data from FIREBIRD‐II consist of 5 differential energy channels between 200 keV and 1 MeV and a 1 MeV integral channel. This covers an energy range that has not been well studied from low Earth orbit with good energy and time resolution. This study aims to improve the understanding of the scattering mechanism behind electron microbursts by investigating their spectral properties and their relationship with the equatorial electron population under different geomagnetic conditions. Microbursts are identified in the region of the North Atlantic where FIREBIRD only observes electrons in the bounce loss cone. The electron flux and exponential energy spectrum of each microburst are calculated using a FIREBIRD instrument response modeled in GEANT4 (GEometry ANd Tracking) and compared with the near‐equatorial electron spectra measured by the Van Allen Probes. Microbursts occurring when the Auroral Electrojet (AE) index is enhanced tend to carry more electrons with relatively higher energies. The microburst scattering mechanism is more efficient at scattering electrons with lower energies; however, the difference in scattering efficiency between low and high energy is reduced during periods of enhanced AE.