Bursts Of Electrical Activity Research Articles

Amperometric bio-sensing of lactate and oxygen concurrently with local field potentials during status epilepticus

Epilepsy is a prevalent neurological disorder with a complex pathogenesis and unpredictable nature, presenting limited treatment options in >30 % of affected individuals. Neurometabolic abnormalities have been observed in epilepsy patients, suggesting a disruption in the coupling between neural activity and energy metabolism in the brain. In this study, we employed amperometric biosensors based on a modified carbon fiber microelectrode platform to directly and continuously measure lactate and oxygen dynamics in the brain extracellular space. These biosensors demonstrated high sensitivity, selectivity, and rapid response time, enabling in vivo measurements with high temporal and spatial resolution. In vivo recordings in the cortex of anaesthetized rats revealed rapid and multiphasic fluctuations in extracellular lactate and oxygen levels following neuronal stimulation with high potassium. Furthermore, real-time measurement of lactate and oxygen concentration dynamics concurrently with network electrical activity during status epilepticus induced by 4-aminopyridine (4-AP) demonstrated phasic changes in lactate levels that correlated with bursts of electrical activity, while tonic levels of lactate remained stable during seizures. This study highlights the complex interplay between lactate dynamics, electrical activity, and oxygen utilization in epileptic seizures.

Symbiosis of Electrical and Metabolic Oscillations in Pancreatic β-Cells.

Insulin is secreted in a pulsatile pattern, with important physiological ramifications. In pancreatic β-cells, which are the cells that synthesize insulin, insulin exocytosis is elicited by pulses of elevated intracellular Ca2+ initiated by bursts of electrical activity. In parallel with these electrical and Ca2+ oscillations are oscillations in metabolism, and the periods of all of these oscillatory processes are similar. A key question that remains unresolved is whether the electrical oscillations are responsible for the metabolic oscillations via the effects of Ca2+, or whether the metabolic oscillations are responsible for the electrical oscillations due to the effects of ATP on ATP-sensitive ion channels? Mathematical modeling is a useful tool for addressing this and related questions as modeling can aid in the design of well-focused experiments that can test the predictions of particular models and subsequently be used to improve the models in an iterative fashion. In this article, we discuss a recent mathematical model, the Integrated Oscillator Model (IOM), that was the product of many years of development. We use the model to demonstrate that the relationship between calcium and metabolism in beta cells is symbiotic: in some contexts, the electrical oscillations drive the metabolic oscillations, while in other contexts it is the opposite. We provide new insights regarding these results and illustrate that what might at first appear to be contradictory data are actually compatible when viewed holistically with the IOM.

Susceptibility of pentylenetetrazole-induced seizures in mice with Cereblon gene knockout

Epilepsy is a neurological disorder characterized by unpredictable seizures, which are bursts of electrical activity that tempo-rarily affect the brain. Cereblon (CRBN), a DCAFs (DDB1 and CUL4associated factors), is a well-established protein associated with human mental retardation. Being a substrate receptor of the cullin-RING E3 ubiquitin ligase (CRL) 4 complex, CRBN mediates ubiquitination of several substrates and conducts multiple biological processes. In the central nervous system, the large-conductance Ca2+-activated K+ (BKCa) channel, which is the substrate of CRBN, is an important regulator of epilepsy. Despite the functional role and importance of CRBN in the brain, di-rect injection of pentylenetetrazole (PTZ) to induce seizures in CRBN knock-out mice has not been challenged. In this study, we investigated the effect of PTZ in CRBN knock-out mice. Here, we demonstrate that, compared with WT mice, CRBN knock-out mice do not show the intensification of seizures by PTZ induction. Moreover, electroencephalography recordings were also performed in the brains of both WT and CRBN knockout mice to identify the absence of significant differences in the pattern of seizure activities. Consistently, immunoblot analysis for validating the protein level of the CRL4 complex containing CRBN (CRL4Crbn) in the mouse brain was carried out. Taken together, we found that the deficiency of CRBN does not affect PTZ-induced seizure.

Modeling Compact Intracloud Discharge (CID) as a Streamer Burst

Narrow Bipolar Pulses are generated by bursts of electrical activity in the cloud and these are referred to as Compact Intracloud Discharges (CID) or Narrow Bipolar Events in the current literature. These discharges usually occur in isolation without much electrical activity before or after the event, but sometimes they are observed to initiate lightning flashes. In this paper, we have studied the features of CIDs assuming that they consist of streamer bursts without any conducting channels. A typical CID may contain about 109 streamer heads during the time of its maximum growth. A CID consists of a current front of several nanosecond duration that travels forward with the speed of the streamers. The amplitude of this current front increases initially during the streamer growth and decays subsequently as the streamer burst continues to propagate. Depending on the conductivity of the streamer channels, there could be a low-level current flow behind this current front which transports negative charge towards the streamer origin. The features of the current associated with the CID are very different from those of the radiation field that it generates. The duration of the radiation field of a CID is about 10–20 μs, whereas the duration of the propagating current pulse associated with the CID is no more than a few nanoseconds in duration. The peak current of a CID is the result of a multitude of small currents associated with a large number of streamers and, if all the forward moving streamer heads are located on a single horizontal plane, the cumulative current that radiates at its peak value could be about 108 A. On the other hand, the current associated with an individual streamer is no more than a few hundreds of mA. However, if the location of the forward moving streamer heads are spread in a vertical direction, the peak current can be reduced considerably. Moreover, this large current is spread over an area of several tens to several hundreds of square meters. The study shows that the streamer model of the CID could explain the fine structure of the radiation fields present both in the electric field and electric field time derivative.

Intracellular manganese enhanced MRI signals reflect the frequency of action potentials in Aplysia neurons

BackgroundManganese-enhanced magnetic resonance imaging (MEMRI) is an increasingly popular alternative to standard functional MRI methods in animal studies. The contrast in MEMRI images is based on the accumulation of Mn2+ ions inside neurons, and, since manganese can serve as calcium analogue, this accumulation reflects calcium dynamics providing versatile information about brain neuroarchitecture and functionality. However, despite its use as a functional imaging tool, the exact relationship between the MEMRI signal and neuronal activity remains elusive. New methodIn order to better understand the mechanisms underlying Mn2+ accumulation resulting in MEMRI signal enhancement we investigated single neuron responses of isolated Aplysia buccal ganglia subjected to chemical (dopamine) or electrical stimulation of an input nerve (oesophageal nerve). The elicited electrical activity that represents a fictive feeding was recorded with electrophysiological methods and the Mn2+ uptake in individual neurons was evaluated with MEMRI at 17.2T. Results & comparison with existing method(s)We show a positive correlation between bursts of electrical activity and MEMRI signal intensity in identified neurons and demonstrate that the MEMRI signal reflects mainly fast and high membrane depolarization processes such as action potentials, and it is not sensitive to slow and small membrane depolarizations, such as post-synaptic potentials.

Analysis of Interacting Local Oscillation Mechanisms in Three-Timescale Systems

Oscillations in slow/fast systems can be generated locally in phase space from either slow passage of trajectories through fast subsystem Hopf bifurcations, or from solutions tunnelling through twisted slow manifolds due to folded node singularities. In the two-timescale context, the fast subsystem Hopf and folded singularity remain as separate entities. In the three-timescale context, however, these singularities can interact, which allows for an interesting mixing of timescales and complex oscillatory dynamics. To further compound the problem, the folded singularity in these three-timescale problems is always close to the folded saddle-node regime, where canard theory breaks down. In this work, we examine a natural scenario in three-timescale systems where the fast subsystem Hopf and a folded node coexist and interact, as seen for instance in models for the electrical bursting activity in pituitary lactotrophs and for the secretion of gonadotropin releasing hormone by hypothalamic neurons. We analyze a novel type of fold-related singularity of the three-timescale system, which requires three timescales and which we call the canard-delayed-Hopf (CDH) singularity, from which the Hopf and folded node unfold, in order to determine properties of the local oscillatory behavior. We establish three types of results: (i) we prove the existence of canard solutions near the CDH singularity, which we show occurs naturally in the three-timescale context, (ii) we obtain an upper bound on the number of canard solutions and hence on the amount of rotation, and (iii) we estimate the bifurcation delay induced by passage of trajectories through the canard/fast-subsystem-Hopf region. (An erratum is attached.)

Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations.

Glioma patients often suffer from epileptic seizures because of the tumor's impact on the brain physiology. Using the rat glioma cell line C6 as a model system, we performed long-term live recordings of the electrical activity of glioma populations in an ultrasensitive detection method. The transducer exploits large-area electrodes that maximize double-layer capacitance, thus increasing the sensitivity. This strategy allowed us to record glioma electrical activity. We show that although glioma cells are nonelectrogenic, they display a remarkable electrical burst activity in time. The low-frequency current noise after cell adhesion is dominated by the flow of Na+ ions through voltage-gated ion channels. However, after an incubation period of many hours, the current noise markedly increased. This electric bursting phenomenon was not associated with apoptosis because the cells were viable and proliferative during the period of increased electric activity. We detected a rapid cell culture medium acidification accompanying this event. By using specific inhibitors, we showed that the electrical bursting activity was prompted by extracellular pH changes, which enhanced Na+ ion flux through the psalmotoxin 1-sensitive acid-sensing ion channels. Our model of pH-triggered bursting was unambiguously supported by deliberate, external acidification of the cell culture medium. This unexpected, acidosis-driven electrical activity is likely to directly perturb, in vivo, the functionality of the healthy neuronal network in the vicinity of the tumor bulk and may contribute to seizures in glioma patients.

PP14.2 – 2563: Early electrical brain activity in preterm neonates with very low birth weight with prolonged respiratory therapy without clinical and ultrasound features of acute brain damages

There is prevalence of neurodevelopmental impairment in children born extremely premature and in recent years it is observed and considers as a result of acute brains damage occurring during the first postnatal weeks. Development of methods that enable early identification of functional disorders and risk of acute brain injury in preterm infants is obvious necessary in NICU (neonatal intensive care unit). Aim To demonstrate the physiological features of brain activity in the early neonatal period in preterm infants receiving respiratory therapy (prolonger mechanical ventilation), with very low birth weights and gestational age up to 32 weeks, in acute neonatal period without clinical and brains images sings detecting by cranial ultrasound. Subjects: We studied 10 neurologically healthy preterm babies with prolonged mechanically ventilation, they gestation age was between 27–30 weeks (averages M=28.6±3.59 weeks), with averages weight birth (M) 1077±359 grams. Nobody obtained sedation therapy. Methods Scalp EEG was recorded with 8 electrodes on 3–5 days after birth, duration – 1 hour. Repeated cranial ultrasound investigations (cUS) were performed on days1, 3 and 7 and 4 weeks after birth. Results Structural brain changes has not been detected by cUS in all patients. Early EEG activity in all preterm patients consists of patterns discontinue: inter burst interval (IBI) and burst of electrical activity. Maximum duration of IBI was 8–25 sec, (M=15.8±10.45 sec), minimum duration – 4–12 sec (M=8, 2±6.28 s). Averages time of IBI in preterm infants with very low birth weight was 6–18.5 sec (M=11.4±8.97). Conclusion Study demonstrates that the electro-cortical background activity, in the early neonatal period in preterm infants with very low birth weight and receiving respiratory therapy (prolonger mechanical ventilation), without clinical and neuroimigine damage sings is presented by trace discontinue. The average durations of inter burst interval is 11.4±8.97 s.

Discrete Coupling and Synchronization in the Insulin Release in the Mathematical Model of theβCells

The synchronization phenomenon that occurs in the Langerhans islets among pancreaticβcells is an interesting topic because these cells are responsible for the release of insulin in the blood stream. The aim of this work is to generate in-phase bursting electrical activity (BEA) inβcells with different behaviors such as active, inactive, and continuous spiking cells based on mathematical models using a discrete time coupling. The approach considers two steps, the former is a mechanism on how to forceβcells to switch from silent phase to active, the latter is based on how to deal with in phase synchronization between activeβcells. The coupling signal is triggered in discrete events caused by the crossing of a threshold of an activeβcell which is given or defined by a Poincaré plane. The coupling on the inactive cells is applied to the state in which are the concentrations of agents which regulate the BEA. Based on numerical simulations, synchronization in the insulin release is obtained fromβcells with different behaviors.

Spiking Signatures of Spontaneous Activity Bursts in Hippocampal Cultures

Dense dissociated hippocampal cultures are known to generate spontaneous bursting electrical activity which can be recorded by multielectrode arrays. We have analyzed spatio-temporal profiles of the distribution of spikes in the bursts recorded after 2 weeks in vitro. We have found a statistically significant similarity between the spiking patterns in sequential bursting events, we refer to these spiking patterns as spiking signatures. Such spiking signatures may appear in different parts of the bursts, including the activation patterns – the first spike times in the bursts, and deactivation patterns – the last spike times in the bursts. Moreover, these patterns may display apparent time scaling, e.g., they may be replayed in the subsequent bursts at different speeds, while preserving the spiking order. We discuss how such properties of the bursts may be associated with the formation of repeatable signaling pathways in cultured networks in vitro.

Using State-Space Model with Regime Switching to Represent the Dynamics of Facial Electromyography (EMG) Data

Facial electromyography (EMG) is a useful physiological measure for detecting subtle affective changes in real time. A time series of EMG data contains bursts of electrical activity that increase in magnitude when the pertinent facial muscles are activated. Whereas previous methods for detecting EMG activation are often based on deterministic or externally imposed thresholds, we used regime-switching models to probabilistically classify each individual’s time series into latent “regimes” characterized by similar error variance and dynamic patterns. We also allowed the association between EMG signals and self-reported affect ratings to vary between regimes and found that the relationship between these two markers did in fact vary over time. The potential utility of using regime-switching models to detect activation patterns in EMG data and to summarize the temporal characteristics of EMG activities is discussed.

Spike patterns similarity in bursts of spontaneous activity in hippocampal cultures using MEA

Spike patterns similarity in bursts of spontaneous activity in hippocampal cultures using MEA

How nurses can help epilepsy patients take control over managing their condition

Epilepsy is the most common neurological condition in the world after migraine. It is defined as the tendency to experience recurrent seizures. A seizure is caused by a sudden burst of electrical activity in the brain causing a temporary disruption to the normal messages passing through brain cells. There are about 40 different types of seizure, classified into generalized seizures and partial seizures.

Seasonal changes in peptide, receptor and ion channel mRNA expression in the caudal neurosecretory system of the European flounder ( Platichthys flesus)

The caudal neurosecretory system (CNSS) of the euryhaline flounder Platichthys flesus has suggested roles in osmoregulatory, reproductive and nutritional adaptation, as fish migrate between seawater (winter) and brackish/freshwater (summer) environments. This study examined seasonal changes in mRNA expression profile of functionally important genes in the CNSS. cDNAs encoding neuropeptides, receptors and ion channels were cloned by reverse transcriptase polymerase chain reaction (RT-PCR) and screening of a flounder CNSS cDNA library. The expression profile of cloned genes was determined by real-time RT-PCR at 2-month intervals throughout the year in CNSS from seawater-adapted fish. Plasma cortisol (measured by radioimmunoassay) showed a peak in April, the time of spawning. Expression levels of mRNA for peptides urotensins I and II (UI, UII) and corticotropin releasing factor (CRF) all showed a seasonal cycle, with lowest expression in April and highest in August–October. The expression of CRF2(UI), UT(UII) and CRF1 receptors was not correlated with corresponding peptide expression. Receptors for potential neuromodulators of CNSS activity also displayed a seasonal mRNA expression profile. Glucocorticoid, 5-hydroxytryptamine, κ-opioid and glutamate receptor expression peaked around April, suggesting that modulation of electrical activity of the neurosecretory Dahlgren cells is of particular importance at this time. Expression of mRNA for L-type Ca 2+ and Ca-activated K + channels was lower during the summer months. These channels underlie electrical bursting activity in Dahlgren cells. Ion channel mRNA expression was also lower in CNSS from flounder fully adapted to freshwater as opposed to seawater, consistent with previously reported observations of reduced bursting activity in Dahlgren cells from freshwater-adapted CNSS. These findings support the hypothesis that the CNSS is functionally reprogrammed to cope with changes in physiological challenge as fish migrate between sea and estuaries in winter and spring.

Hyperpolarization-Activated Cation Channels Are Expressed in Rat Hypothalamic Gonadotropin-Releasing Hormone (GnRH) Neurons and Immortalized GnRH Neurons

The current research was conducted to determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN1-4) channels are expressed in gonadotropin-releasing hormone (GnRH) neurons in the female rat hypothalamus and immortalized GnRH neurons (GT1-7 cells). Double-label fluorescence immunohistochemistry was used to colocalize HCN1-4 channels and GnRH in GnRH neurons in the female rat hypothalamus. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemistry were used to analyze HCN channel gene expression in GT1-7 cells. Double-label fluorescence immunohistochemistry showed that 43% of hypothalamic GnRH neurons immunostained for HCN2 and 90% of GnRH neurons immunostained for HCN3. RT-PCR and Western blot showed expression of all four HCN channel subunits in GT1-7 cells. Double-label immunocytochemistry showed cytoplasmic immunostaining of HCN2 and HCN3 in GT1-7 cells. This study demonstrates for the first time that HCN channels are expressed in GnRH neurons in the rat hypothalamus and GT1-7 cells. Our research supports the hypothesis that HCN channels may be involved in electrical bursting activity and pulsatile GnRH secretion in endogenous GnRH neurons and GT1-7 cells.

Chemosensory pathways in the capitate tentacles of the hydroid Cladonema

The introduction of an extract of Artemia into the sea water bathing tentacles from the hydroid Cladonema triggers a burst of electrical activity that can be recorded intracellularly from cnidocytes in the capitate tentacles. These bursts, which are composed of a variety of events, including action potentials and EPSPs, are Ca2+ dependent, and are abolished by pretreatment with NiCl2, suggesting that voltage-gated Ca2+ channels are involved in their generation or transmission. Intracellular injection of Lucifer Yellow and recordings from pairs of cnidocytes reveal that the cnidocytes are electrically coupled to one another, but that they are not uncoupled by heptanol. The role of these chemosensory pathways in priming the cnidocytes for discharge is discussed.

Return Map Characterizations for a Model of Bursting with Two Slow Variables

Various physiological systems display bursting electrical activity (BEA). There exist numerous three‐variable models to describe this behavior. However, higher‐dimensional models with two slow processes have recently been used to explain qualitative features of the BEA of some experimentally observed systems [T. Chay and D. Cook, Math. Biosci., 90 (1988), pp. 139–153; P. Smolen and J. Keizer, J. Memb. Biol., 127 (1992), pp. 9–19; R. Bertram et al., Biophys. J., 79 (2000), pp. 2880–2892; R. Bertram et al., Biophys. J., 68 (1995), pp. 2323–2332; J. Keizer and P. Smolen, Proc. Nat. Acad. Sci. USA, 88 (1991), pp. 3897–3901]. In this paper we present a model with two slow and two fast variables. For some parameter values the system has stable equilibria, while for other values there exist bursting solutions. Singular perturbation methods are used to define a one‐dimensional return map, wherein fixed points correspond to singular bursting solutions. We analytically demonstrate that bursting solutions may exist ...

Effect of Light Wavelength and Osmolality on the Swimming of Cercariae of Proterometra macrostoma (Digenea: Azygiidae)

The objectives of this study were to describe the effect of light wavelength and osmolality on the vertical swimming distance of the cercaria of Proterometra macrostoma. Significant differences were found in the average swimming distances and electrical burst activity in the tail of cercariae exposed to red vs. blue, green or white light, but no difference was observed when the last three colors were compared to one another with one exception. Cercarial swimming decreased slightly after 12 hr PE (post-exposure) in artificial pond water (15 mOsm) and artificial snail water (102 mOsm). By contrast, a significant reduction in swimming distance was observed in distilled water (0 mOsm) and artificial snail water with two different concentrations of mannitol (180 and 267 mOsm).

Intra- and Inter-Islet Synchronization of Metabolically Driven Insulin Secretion

Insulin secretion from pancreatic β-cells is pulsatile with a period of 5–10 min and is believed to be responsible for plasma insulin oscillations with similar frequency. To observe an overall oscillatory insulin profile it is necessary that the insulin secretion from individual β-cells is synchronized within islets, and that the population of islets is also synchronized. We have recently developed a model in which pulsatile insulin secretion is produced as a result of calcium-driven electrical oscillations in combination with oscillations in glycolysis. We use this model to investigate possible mechanisms for intra-islet and inter-islet synchronization. We show that electrical coupling is sufficient to synchronize both electrical bursting activity and metabolic oscillations. We also demonstrate that islets can synchronize by mutually entraining each other by their effects on a simple model “liver,” which responds to the level of insulin secretion by adjusting the blood glucose concentration in an appropriate way. Since all islets are exposed to the blood, the distributed islet-liver system can synchronize the individual islet insulin oscillations. Thus, we demonstrate how intra-islet and inter-islet synchronization of insulin oscillations may be achieved.

Role of the axodendritic tree in the functioning of Helix bursting neurons: generation of pacemaker activity and propagation of action potentials along the axon

The purpose of this study was to determine the role of the axodendritic tree in the generation of bursting pacemaker activity in the identified Helix RPa1 neuron, which is homologous to the Aplysia R15 cell, and propagation of action potentials along the axons. In doing so, I used recording of RPa1 neuron electrical activity after cutting off the right or left parietovisceral connections, the two-electrode voltage-clamp technique, registration of electrical activity of visceral nerve containing RPa1 axon branches, isolation of the RPa1 neuron and puff application of oxytocin on it. Cutting of the right (but not left) parietovisceral connection in all cases (more than 15 preparations) evoked complete disappearance of bursting pacemaker activity in the RPa1 neuron and hyperpolarization of its membrane potential up to −65 to −67 mV. Such silent state of the RPa1 neuron was maintained after its complete isolation from the ganglion. The described cutting did not result in a change of bursting activity of the pacemaker neuron V7 located in the visceral ganglion, although isolation of the V7 neuron also eliminated its own activity. Puff application of oxytocin (10 μM in a micropipette) on to the RPa1 neuron both after cutting the right parietovisceral connection or isolation of the neuron from the ganglion resulted in all cases (more than 10 cells) in transient depolarization with development of beating, oscillatory or bursting activity. Voltage clamping of RPa1 soma in the intact ganglion at a level close to zero membrane current sometimes, and, as a rule, at a more depolarized level, revealed bursting-like oscillations of membrane current, reflecting electrical bursting activity in the unclamped remote region of a neuron, most likely in the dendritic tree. Voltage clamping of RPa1 soma possessing bursting activity reveals bursting-like oscillation of membrane current and prevents propagation of corresponding axon action potentials in the visceral nerve. Controversially, clamping of RPa1 soma possessing beating activity exhibits a beating-like oscillation of membrane current and does not prevent propagation of corresponding action potentials in the nerve. Within the framework of the developed hypothesis that persistent bursting pacemaker activity of the RPa1 neuron is due to a constant activation of its peptidergic synaptic inputs [Kononenko N. I. (1993) Comp. Biochem. Physiol. 106A, 135–147], the experimental results were interpreted in the manner that these synapses and, correspondingly, the locus of electrical bursting activity generation, are localized on the dendritic tree of the RPa1 neuron mainly or possibly exclusively in the visceral ganglion. It is hypothesized that bursting and beating neuronal activities are due to functioning of different loci of the dendritic tree, regarding their electrical relations with axon branches.