Electrophysiology of neurones of the inferior mesenteric ganglion of the cat.

PubMed

Julé, Y; Szurszewski, J H

1983-11-01

Intracellular recordings were obtained from cells in vitro in the inferior mesenteric ganglia of the cat. Neurones could be classified into three types: non-spontaneous, irregular discharging and regular discharging neurones. Non-spontaneous neurones had a stable resting membrane potential and responded with action potentials to indirect preganglionic nerve stimulation and to intracellular injection of depolarizing current. Irregular discharging neurones were characterized by a discharge of excitatory post-synaptic potentials (e.p.s.p.s.) which sometimes gave rise to action potentials. This activity was abolished by hexamethonium bromide, chlorisondamine and d-tubocurarine chloride. Tetrodotoxin and a low Ca2+ -high Mg2+ solution also blocked on-going activity in irregular discharging neurones. Regular discharging neurones were characterized by a rhythmic discharge of action potentials. Each action potential was preceded by a gradual depolarization of the intracellularly recorded membrane potential. Intracellular injection of hyperpolarizing current abolished the regular discharge of action potential. No synaptic potentials were observed during hyperpolarization of the membrane potential. Nicotinic, muscarinic and adrenergic receptor blocking drugs did not modify the discharge of action potentials in regular discharging neurones. A low Ca2+ -high Mg2+ solution also had no effect on the regular discharge of action potentials. Interpolation of an action potential between spontaneous action potentials in regular discharging neurones reset the rhythm of discharge. It is suggested that regular discharging neurones were endogenously active and that these neurones provided synaptic input to irregular discharging neurones.

All optical experimental design for neuron excitation, inhibition, and action potential detection

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

2016-03-01

Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

Spike detection, characterization, and discrimination using feature analysis software written in LabVIEW.

PubMed

Stewart, C M; Newlands, S D; Perachio, A A

2004-12-01

Rapid and accurate discrimination of single units from extracellular recordings is a fundamental process for the analysis and interpretation of electrophysiological recordings. We present an algorithm that performs detection, characterization, discrimination, and analysis of action potentials from extracellular recording sessions. The program was entirely written in LabVIEW (National Instruments), and requires no external hardware devices or a priori information about action potential shapes. Waveform events are detected by scanning the digital record for voltages that exceed a user-adjustable trigger. Detected events are characterized to determine nine different time and voltage levels for each event. Various algebraic combinations of these waveform features are used as axis choices for 2-D Cartesian plots of events. The user selects axis choices that generate distinct clusters. Multiple clusters may be defined as action potentials by manually generating boundaries of arbitrary shape. Events defined as action potentials are validated by visual inspection of overlain waveforms. Stimulus-response relationships may be identified by selecting any recorded channel for comparison to continuous and average cycle histograms of binned unit data. The algorithm includes novel aspects of feature analysis and acquisition, including higher acquisition rates for electrophysiological data compared to other channels. The program confirms that electrophysiological data may be discriminated with high-speed and efficiency using algebraic combinations of waveform features derived from high-speed digital records.

Iridium Oxide Nanotube Electrodes for Highly Sensitive and Prolonged Intracellular Measurement of Action Potentials

PubMed Central

Lin, Ziliang Carter; Xie, Chong; Osakada, Yasuko; Cui, Yi; Cui, Bianxiao

2014-01-01

Intracellular recording of action potentials is important to understand electrically-excitable cells. Recently, vertical nanoelectrodes have been developed to achieve highly sensitive, minimally invasive, and large scale intracellular recording. It has been demonstrated that the vertical geometry is crucial for the enhanced signal detection. Here we develop nanoelectrodes made up of nanotubes of iridium oxide. When cardiomyocytes are cultured upon those nanotubes, the cell membrane not only wraps around the vertical tubes but also protrudes deep into the hollow center. We show that this geometry enhances cell-electrode coupling and results in measuring much larger intracellular action potentials. The nanotube electrodes afford much longer intracellular access and are minimally invasive, making it possible to achieve stable recording up to an hour in a single session and more than 8 days of consecutive daily recording. This study suggests that the electrode performance can be significantly improved by optimizing the electrode geometry. PMID:24487777

Median and ulnar muscle and sensory evoked potentials.

PubMed

Felsenthal, G

1978-08-01

The medical literature was reviewed to find suggested clinical applications of the study of the amplitude of evoked muscle action potentials (MAP) and sensory action potentials (SAP). In addition, the literature was reviewed to ascertain the normal amplitude and duration of the evoked MAP and SAP as well as the factors affecting the amplitude: age, sex, temperature, ischemia. The present study determined the normal amplitude and duration of the median and ulnar MAP and SAP in fifty normal subjects. The amplitude of evoked muscle or sensory action potentials depends on multiple factors. Increased skin resistance, capacitance, and impedance at the surface of the recording electrode diminishes the amplitude. Similarly, increased distance from the source of the action potential diminishes its amplitude. Increased interelectrode distance increases the amplitude of the bipolarly recorded sensory action potential until a certain interelectrode distance is exceeded and the diphasic response becomes tri- or tetraphasic. Artifact or poor technique may reduce the potential difference between the recording electrodes or obscure the late positive phase of the action potential and thus diminish the peak to peak amplitude measurement. Intraindividual comparison indicated a marked difference of amplitude in opposite hands. The range of the MAP of the abductor pollicis brevis in one hand was 40.0--100% of the response in the opposite hand. For the abductor digiti minimi, the MAP was 58.5--100% of the response of the opposite hand. The median and ulnar SAP was between 50--100% of the opposite SAP. Consequent to these findings the effect of hand dominance on the amplitude of median and ulnar evoked muscle and sensory action potentials was studied in 41 right handed volunteers. The amplitudes of the median muscle action potential (p less than 0.02) and the median and ulnar sensory action potentials (p less than 0.001) were significantly less in the dominant hand. There was no significant difference between the ulnar muscle action potentials or for the median and ulnar distal motor and sensory latencies in the right and left hands of this group of volunteers.

Reliability of directional information in unsorted spikes and local field potentials recorded in human motor cortex

PubMed Central

Perge, János A.; Zhang, Shaomin; Malik, Wasim Q.; Homer, Mark L.; Cash, Sydney; Friehs, Gerhard; Eskandar, Emad N.; Donoghue, John P.; Hochberg, Leigh R.

2014-01-01

Objective Action potentials and local field potentials (LFPs) recorded in primary motor cortex contain information about the direction of movement. LFPs are assumed to be more robust to signal instabilities than action potentials, which makes LFPs along with action potentials a promising signal source for brain-computer interface applications. Still, relatively little research has directly compared the utility of LFPs to action potentials in decoding movement direction in human motor cortex. Approach We conducted intracortical multielectrode recordings in motor cortex of two persons (T2 and [S3]) as they performed a motor imagery task. We then compared the offline decoding performance of LFPs and spiking extracted from the same data recorded across a one-year period in each participant. Main results We obtained offline prediction accuracy of movement direction and endpoint velocity in multiple LFP bands, with the best performance in the highest (200–400Hz) LFP frequency band, presumably also containing low-pass filtered action potentials. Cross-frequency correlations of preferred directions and directional modulation index showed high similarity of directional information between action potential firing rates (spiking) and high frequency LFPs (70–400Hz), and increasing disparity with lower frequency bands (0–7, 10–40 and 50–65Hz). Spikes predicted the direction of intended movement more accurately than any individual LFP band, however combined decoding of all LFPs was statistically indistinguishable from spike based performance. As the quality of spiking signals (i.e. signal amplitude) and the number of significantly modulated spiking units decreased, the offline decoding performance decreased 3.6[5.65]%/month (for T2 and [S3] respectively). The decrease in the number of significantly modulated LFP signals and their decoding accuracy followed a similar trend (2.4[2.85]%/month, ANCOVA, p=0.27[0.03]). Significance Field potentials provided comparable offline decoding performance to unsorted spikes. Thus, LFPs may provide useful external device control using current human intracortical recording technology. (Clinical trial registration number: NCT00912041) PMID:24921388

Action potentials recorded from bundles of very thin, gray matter axons in rat cerebellar slices using a grease-gap method.

PubMed

Palani, Damodharan; Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna; Raastad, Morten

2012-07-15

We investigated the ability of a grease-gap method to record fast and slow changes of the membrane potential from bundles of gray matter axons. Their membrane potentials are of particular interest because these axons are different from most axons that have been investigated using intra-axonal or gap techniques. One of the main differences is that gray matter axons typically have closely spaced presynaptic specializations, called boutons or varicosities, distributed along their entire paths. In response to electrical activation of bundles of parallel fiber axons we were able to record small (128-416μV) but stable signals that we show most likely represented a fraction of the trans-membrane action potentials. A less-than 100% fraction prevents measurements of absolute values for membrane potentials, but the good signal-to-noise ratio (typically 10-16) allows detection of changes in resting membrane potential, action potentials and their after-potentials. Because very little is known about the shape of action potentials and after-potentials in these axons we used several independent methods to make it likely that the grease-gap signal was of intra-axonal origin. We demonstrate the utility of the method by showing that the action potentials in cerebellar parallel fibers and hippocampal Schaffer collaterals had a slowly decaying, depolarized after-potential. The method is ideal for pharmacological tests, which we demonstrate by showing that the slow after-potential was sensitive to 4-AP, and that the membrane potential was reduced by 200μM Ba(2+). Copyright © 2012 Elsevier B.V. All rights reserved.

[Functional organization and structure of the serotonergic neuronal network of terrestrial snail].

PubMed

Nikitin, E S; Balaban, P M

2011-01-01

The extension of knowledge how the brain works requires permanent improvement of methods of recording of neuronal activity and increase in the number of neurons recorded simultaneously to better understand the collective work of neuronal networks and assemblies. Conventional methods allow simultaneous intracellular recording up to 2-5 neurons and their membrane potentials, currents or monosynaptic connections or observation of spiking of neuronal groups with subsequent discrimination of individual spikes with loss of details of the dynamics of membrane potential. We recorded activity of a compact group of serotonergic neurons (up to 56 simultaneously) in the ganglion of a terrestrial mollusk using the method of optical recording of membrane potential that allowed to record individual action potentials in details with action potential parameters and to reveal morphology of the neurons rcorded. We demonstrated clear clustering in the group in relation with the dynamics of action potentials and phasic or tonic components in the neuronal responses to external electrophysiological and tactile stimuli. Also, we showed that identified neuron Pd2 could induce activation of a significant number of neurons in the group whereas neuron Pd4 did not induce any activation. However, its activation is delayed with regard to activation of the reacting group of neurons. Our data strongly support the concept of possible delegation of the integrative function by the network to a single neuron.

Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

PubMed Central

Connors, S. P.; Gill, E. W.; Terrar, D. A.

1992-01-01

1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1393293

TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

PubMed

Hof, Thomas; Sallé, Laurent; Coulbault, Laurent; Richer, Romain; Alexandre, Joachim; Rouet, René; Manrique, Alain; Guinamard, Romain

2016-01-15

The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2013 CFR

2013-04-01

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21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2011 CFR

2011-04-01

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21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2010 CFR

2010-04-01

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21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2012 CFR

2012-04-01

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21 CFR 820.100 - Corrective and preventive action.

Code of Federal Regulations, 2014 CFR

2014-04-01

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An Integrated Circuit for Simultaneous Extracellular Electrophysiology Recording and Optogenetic Neural Manipulation

PubMed Central

Chen, Chang Hao; McCullagh, Elizabeth A.; Pun, Sio Hang; Mak, Peng Un; Vai, Mang I; Mak, Pui In; Klug, Achim; Lei, Tim C.

2017-01-01

The ability to record and to control action potential firing in neuronal circuits of the brain is critical to understand how the brain functions on the cellular and network levels. Recent development of optogenetic proteins allows direct stimulation or inhibition of action potential firing of neurons upon optical illumination. In this paper, we combined a low-noise and high input impedance (or low input capacitance) neural recording amplifier, and a high current laser/LED driver in a monolithic integrated circuit (IC) for simultaneous neural recording and optogenetic neural control. The low input capacitance of the amplifier (9.7 pF) was achieved through adding a dedicated unity gain input stage optimized for high impedance metal electrodes. The input referred noise of the amplifier was measured to be 4.57 µVrms, which is lower than the estimated thermal noise of the metal electrode. Thus, action potentials originating from a single neuron can be recorded with a signal-to-noise ratio of ~6.6. The LED/laser current driver delivers a maximum current of 330 mA to generate adequate light for optogenetic control. We experimentally tested the functionality of the IC with an anesthetized Mongolian gerbil and recorded auditory stimulated action potentials from the inferior colliculus. Furthermore, we showed that spontaneous firing of 5th (trigeminal) nerve fibers was inhibited using the optogenetic protein Halorhodopsin. A noise model was also derived including the equivalent electronic components of the metal electrode and the high current driver to guide the design. PMID:28221990

Optical recording of action potentials and other discrete physiological events: a perspective from signal detection theory.

PubMed

Sjulson, Lucas; Miesenböck, Gero

2007-02-01

Optical imaging of physiological events in real time can yield insights into biological function that would be difficult to obtain by other experimental means. However, the detection of all-or-none events, such as action potentials or vesicle fusion events, in noisy single-trial data often requires a careful balance of tradeoffs. The analysis of such experiments, as well as the design of optical reporters and instrumentation for them, is aided by an understanding of the principles of signal detection. This review illustrates these principles, using as an example action potential recording with optical voltage reporters.

Effects of premature stimulation on HERG K+ channels

PubMed Central

Lu, Yu; Mahaut-Smith, Martyn P; Varghese, Anthony; Huang, Christopher L-H; Kemp, Paul R; Vandenberg, Jamie I

2001-01-01

The unusual kinetics of human ether-à-go-go-related gene (HERG) K+ channels are consistent with a role in the suppression of arrhythmias initiated by premature beats. Action potential clamp protocols were used to investigate the effect of premature stimulation on HERG K+ channels, transfected in Chinese hamster ovary cells, at 37 °C. HERG K+ channel currents peaked during the terminal repolarization phase of normally paced action potential waveforms. However, the magnitude of the current and the time point at which conductance was maximal depended on the type of action potential waveform used (epicardial, endocardial, Purkinje fibre or atrial). HERG K+ channel currents recorded during premature action potentials consisted of an early transient outward current followed by a sustained outward current. The magnitude of the transient current component showed a biphasic dependence on the coupling interval between the normally paced and premature action potentials and was maximal at a coupling interval equivalent to 90% repolarization (APD90) for ventricular action potentials. The largest transient current response occurred at shorter coupling intervals for Purkinje fibre (APD90– 20 ms) and atrial (APD90– 30 ms) action potentials. The magnitude of the sustained current response following premature stimulation was similar to that recorded during the first action potential for ventricular action potential waveforms. However, for Purkinje and atrial action potentials the sustained current response was significantly larger during the premature action potential than during the normally paced action potential. A Markov model that included three closed states, one open and one inactivated state with transitions permitted between the pre-open closed state and the inactivated state, successfully reproduced our results for the effects of premature stimuli, both during square pulse and action potential clamp waveforms. These properties of HERG K+ channels may help to suppress arrhythmias initiated by early afterdepolarizations and premature beats in the ventricles, Purkinje fibres or atria. PMID:11744759

Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

PubMed

Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

2018-06-01

Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential in the Aδ neurons, underlying a sensory generation mechanism of dentinal pain. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

High-resolution non-contact measurement of the electrical activity of plants in situ using optical recording

PubMed Central

Zhao, Dong-Jie; Chen, Yang; Wang, Zi-Yang; Xue, Lin; Mao, Tong-Lin; Liu, Yi-Min; Wang, Zhong-Yi; Huang, Lan

2015-01-01

The limitations of conventional extracellular recording and intracellular recording make high-resolution multisite recording of plant bioelectrical activity in situ challenging. By combining a cooled charge-coupled device camera with a voltage-sensitive dye, we recorded the action potentials in the stem of Helianthus annuus and variation potentials at multiple sites simultaneously with high spatial resolution. The method of signal processing using coherence analysis was used to determine the synchronization of the selected signals. Our results provide direct visualization of the phloem, which is the distribution region of the electrical activities in the stem and leaf of H. annuus, and verify that the phloem is the main action potential transmission route in the stems of higher plants. Finally, the method of optical recording offers a unique opportunity to map the dynamic bioelectrical activity and provides an insight into the mechanisms of long-distance electrical signal transmission in higher plants. PMID:26333536

Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome.

PubMed

Tyzio, Roman; Khalilov, Ilgam; Represa, Alfonso; Crepel, Valerie; Zilberter, Yuri; Rheims, Sylvain; Aniksztejn, Laurent; Cossart, Rosa; Nardou, Romain; Mukhtarov, Marat; Minlebaev, Marat; Epsztein, Jérôme; Milh, Mathieu; Becq, Helene; Jorquera, Isabel; Bulteau, Christine; Fohlen, Martine; Oliver, Viviana; Dulac, Olivier; Dorfmüller, Georg; Delalande, Olivier; Ben-Ari, Yehezkel; Khazipov, Roustem

2009-08-01

The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies. Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery. Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many cells spontaneously fired action potentials at a rate proportional to the level of neuronal depolarization. The reversal potential for GABA-activated currents, assessed by cell-attached single channel recordings, was close to the resting membrane potential. All spontaneously firing neurons recorded in cell-attached mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous epileptiform activity in the form of recurrent population bursts was suppressed by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had little effect on epileptiform activity. SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex.

Back-Propagation of Physiological Action Potential Output in Dendrites of Slender-Tufted L5A Pyramidal Neurons

PubMed Central

Grewe, Benjamin F.; Bonnan, Audrey; Frick, Andreas

2009-01-01

Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signaling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related ‘barrel cortex’. Our data provide evidence that the temporal structure of physiological action potential patterns is crucial for an effective invasion of the main apical dendrites up to the major branch point. Both the critical frequency enabling action potential trains to invade efficiently and the dendritic calcium profile changed during postnatal development. In contrast to the main apical dendrite, the more passive properties of the short basal and apical tuft dendrites prevented an efficient back-propagation. Various Ca2+ channel types contributed to the enhanced calcium signals during high-frequency firing activity, whereas A-type K+ and BKCa channels strongly suppressed it. Our data support models in which the interaction of synaptic input with action potential output is a function of the timing, rate and pattern of action potentials, and dendritic location. PMID:20508744

An intracellular analysis of the visual responses of neurones in cat visual cortex.

PubMed Central

Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity. PMID:1804981

Rapid time course of action potentials in spines and remote dendrites of mouse visual cortex neurons.

PubMed

Holthoff, Knut; Zecevic, Dejan; Konnerth, Arthur

2010-04-01

Axonally initiated action potentials back-propagate into spiny dendrites of central mammalian neurons and thereby regulate plasticity at excitatory synapses on individual spines as well as linear and supralinear integration of synaptic inputs along dendritic branches. Thus, the electrical behaviour of individual dendritic spines and terminal dendritic branches is critical for the integrative function of nerve cells. The actual dynamics of action potentials in spines and terminal branches, however, are not entirely clear, mostly because electrode recording from such small structures is not feasible. Additionally, the available membrane potential imaging techniques are limited in their sensitivity and require substantial signal averaging for the detection of electrical events at the spatial scale of individual spines. We made a critical improvement in the voltage-sensitive dye imaging technique to achieve multisite recordings of backpropagating action potentials from individual dendritic spines at a high frame rate. With this approach, we obtained direct evidence that in layer 5 pyramidal neurons from the visual cortex of juvenile mice, the rapid time course of somatic action potentials is preserved throughout all cellular compartments, including dendritic spines and terminal branches of basal and apical dendrites. The rapid time course of the action potential in spines may be a critical determinant for the precise regulation of spike timing-dependent synaptic plasticity within a narrow time window.

Local transmural action potential gradients are absent in the isolated, intact dog heart but present in the corresponding coronary-perfused wedge.

PubMed

Boukens, Bastiaan J; Meijborg, Veronique M F; Belterman, Charly N; Opthof, Tobias; Janse, Michiel J; Schuessler, Richard B; Coronel, Ruben; Efimov, Igor R

2017-05-01

The left ventricular (LV) coronary-perfused canine wedge preparation is a model commonly used for studying cardiac repolarization. In wedge studies, transmembrane potentials typically are recorded; whereas, extracellular electrical recordings are commonly used in intact hearts. We compared electrically measured activation recovery interval (ARI) patterns in the intact heart with those recorded at the same location in the LV wedge preparation. We also compared electrically recorded and optically obtained ARIs in the LV wedge preparation. Five Langendorff-perfused canine hearts were paced from the right atrium. Local activation and repolarization times were measured with eight transmural needle electrodes. Subsequently, left ventricular coronary-perfused wedge preparations were prepared from these hearts while the electrodes remained in place. Three electrodes remained at identical positions as in the intact heart. Both electrograms and optical action potentials were recorded (pacing cycle length 400-4000 msec) and activation and repolarization patterns were analyzed. ARIs found in the subepicardium were shorter than in the subendocardium in the LV wedge preparation but not in the intact heart. The transmural ARI gradient recorded at the cut surface of the wedge was not different from that recorded internally. ARIs recorded internally and at the cut surface in the LV wedge preparation, both correlated with optically recorded action potentials. ARI and RT gradients in the LV wedge preparation differed from those in the intact canine heart, implying that those observations in human LV wedge preparations also should be extrapolated to the intact human heart with caution. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Membrane Potentials of the Lobster Giant Axon Obtained by Use of the Sucrose-Gap Technique

PubMed Central

Julian, Fred J.; Moore, John W.; Goldman, David E.

1962-01-01

A method similar to the sucrose-gap technique introduced be Stäpfli is described for measuring membrane potential and current in singly lobster giant axons (diameter about 100 micra). The isotonic sucrose solution used to perfuse the gaps raises the external leakage resistance so that the recorded potential is only about 5 per cent less than the actual membrane potential. However, the resting potential of an axon in the sucrose-gap arrangement is increased 20 to 60 mv over that recorded by a conventional micropipette electrode when the entire axon is bathed in sea water. A complete explanation for this effect has not been discovered. The relation between resting potential and external potassium and sodium ion concentrations shows that potassium carries most of the current in a depolarized axon in the sucrose-gap arrangement, but that near the resting potential other ions make significant contributions. Lowering the external chloride concentration decreases the resting potential. Varying the concentration of the sucrose solution has little effect. A study of the impedance changes associated with the action potential shows that the membrane resistance decreases to a minimum at the peak of the spike and returns to near its initial value before repolarization is complete (a normal lobster giant axon action potential does not have an undershoot). Action potentials recorded simultaneously by the sucrose-gap technique and by micropipette electrodes are practically superposable. PMID:14452759

Cellular mechanisms of desynchronizing effects of hypothermia in an in vitro epilepsy model.

PubMed

Motamedi, Gholam K; Gonzalez-Sulser, Alfredo; Dzakpasu, Rhonda; Vicini, Stefano

2012-01-01

Hypothermia can terminate epileptiform discharges in vitro and in vivo epilepsy models. Hypothermia is becoming a standard treatment for brain injury in infants with perinatal hypoxic ischemic encephalopathy, and it is gaining ground as a potential treatment in patients with drug resistant epilepsy. However, the exact mechanism of action of cooling the brain tissue is unclear. We have studied the 4-aminopyridine model of epilepsy in mice using single- and dual-patch clamp and perforated multi-electrode array recordings from the hippocampus and cortex. Cooling consistently terminated 4-aminopyridine induced epileptiform-like discharges in hippocampal neurons and increased input resistance that was not mimicked by transient receptor potential channel antagonists. Dual-patch clamp recordings showed significant synchrony between distant CA1 and CA3 pyramidal neurons, but less so between the pyramidal neurons and interneurons. In CA1 and CA3 neurons, hypothermia blocked rhythmic action potential discharges and disrupted their synchrony; however, in interneurons, hypothermia blocked rhythmic discharges without abolishing action potentials. In parallel, multi-electrode array recordings showed that synchronized discharges were disrupted by hypothermia, whereas multi-unit activity was unaffected. The differential effect of cooling on transmitting or secreting γ-aminobutyric acid interneurons might disrupt normal network synchrony, aborting the epileptiform discharges. Moreover, the persistence of action potential firing in interneurons would have additional antiepileptic effects through tonic γ-aminobutyric acid release.

Low doses of alcohol potentiate GABA sub B inhibition of spontaneous activity of hippocampal CA1 neurons in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Criado, J.R.; Thies, R.

1991-03-11

Low doses of alcohol facilitate firing of hippocampal neurons. Such doses also enhance the inhibitory actions of GABA. Alcohol is known to potentiate inhibition via GABA{sub A} receptors. However, the effects of alcohol on GABA{sub B} receptor function are not understood. Spontaneous activity of single units was recorded from CA1 neurons of male rats anesthetized with 1.0% halothane. Electrical recordings and local application of drugs were done with multi-barrel pipettes. CA1 pyramidal neurons fired spontaneous bursts of action potentials. Acute alcohol decreased the interval between bursts, a mild excitatory action. Alcohol also more than doubled the period of complete inhibitionmore » produced by local application of both GABA and baclofen. These data suggest that GABA{sub B}-mediated inhibition is also potentiated by low doses of alcohol.« less

Can optical recordings of membrane potential be used to screen for drug-induced action potential prolongation in single cardiac myocytes?

PubMed

Hardy, M E L; Lawrence, C L; Standen, N B; Rodrigo, G C

2006-01-01

Potential-sensitive dyes have primarily been used to optically record action potentials (APs) in whole heart tissue. Using these dyes to record drug-induced changes in AP morphology of isolated cardiac myocytes could provide an opportunity to develop medium throughout assays for the pharmaceutical industry. Ideally, this requires that the dye has a consistent and rapid response to membrane potential, is insensitive to movement, and does not itself affect AP morphology. We recorded the AP from isolated adult guinea-pig ventricular myocytes optically using di-8-ANEPPS in a single-excitation dual-emission ratiometric system, either separately in electrically field stimulated myocytes, or simultaneously with an electrical AP recorded with a patch electrode in the whole-cell bridge mode. The ratio of di-8-ANEPPS fluorescence signal was calibrated against membrane potential using a switch-clamp to voltage clamp the myocyte. Our data show that the ratio of the optical signals emitted at 560/620 nm is linearly related to voltage over the voltage range of an AP, producing a change in ratio of 7.5% per 100 mV, is unaffected by cell movement and is identical to the AP recorded simultaneously with a patch electrode. However, the APD90 recorded optically in myocytes loaded with di-8-ANEPPS was significantly longer than in unloaded myocytes recorded with a patch electrode (355.6+/-13.5 vs. 296.2+/-16.2 ms; p<0.01). Despite this effect, the apparent IC50 for cisapride, which prolongs the AP by blocking IKr, was not significantly different whether determined optically or with a patch electrode (91+/-46 vs. 81+/-20 nM). These data show that the optical AP recorded ratiometrically using di-8-ANEPPS from a single ventricular myocyte accurately follows the action potential morphology. This technique can be used to estimate the AP prolonging effects of a compound, although di-8-ANEPPS itself prolongs APD90. Optical dyes require less technical skills and are less invasive than conventional electrophysiological techniques and, when coupled to ventricular myocytes, decreases animal usage and facilitates higher throughput assays.

Components of action potential repolarization in cerebellar parallel fibres.

PubMed

Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

2014-11-15

Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

The effects of humoral agents on the myoelectrical activity of the terminal ileum

PubMed Central

Waterfall, W. E.; Brown, B. H.; Duthie, H. L.; Whittaker, G. E.

1972-01-01

Electrical and motor activities of the terminal ileum have been recorded in 25 patients with a permanent ileostomy. Records made within a week of formation of the ileostomy show an increased motor activity which is significantly reduced after four weeks. Intravenous infusion of gastrin, 1 μg/kg-hr, was accompanied by a significant increase in action potentials and in the percentage motility. Conversely, secretin 1 unit/kg-hr was associated with a decrease in action potentials and in percentage motor activity. ImagesFig. 2Fig. 3 PMID:5069728

Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

PubMed

Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

2014-11-05

Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

Auditory thresholds in the American cockroach (Orthoptera: Blattidae): estimates using single-unit and compound-action potential recordings.

PubMed

Decker, T N; Jones, T A; Gold, R E

1989-06-01

Recent commercial suggestions that insect populations can be controlled through the use of ultrasound raises the question of whether or not certain insects have receptors that are sensitive to high-frequency sound. Single neural unit discharges and compound-action potentials were recorded from the ventral nerve cord in the American cockroach, Periplaneta americana L., to constant rise time tone pulses from 100 to 40,000 hertz (Hz). Unit responses and compound-action potentials show that the cockroach is insensitive to sound above approximately 3,000 Hz. Data relating latency of the response to intensity of the stimulus suggest that the cockroach cercal system operates on the principle of energy envelope detection. Decreases in latency likely occur primarily as a result of increases in the rate of membrane depolarization in cercal dendrites.

Phenotyping sensory nerve endings in vitro in the mouse

PubMed Central

Zimmermann, Katharina; Hein, Alexander; Hager, Ulrich; Kaczmarek, Jan Stefan; Turnquist, Brian P; Clapham, David E; Reeh, Peter W

2014-01-01

This protocol details methods to identify and record from cutaneous primary afferent axons in an isolated mammalian skin–saphenous nerve preparation. The method is based on extracellular recordings of propagated action potentials from single-fiber receptive fields. Cutaneous nerve endings show graded sensitivities to various stimulus modalities that are quantified by adequate and controlled stimulation of the superfused skin with heat, cold, touch, constant punctate pressure or chemicals. Responses recorded from single-fibers are comparable with those obtained in previous in vivo experiments on the same species. We describe the components and the setting-up of the basic equipment of a skin–nerve recording station (few days), the preparation of the skin and the adherent saphenous nerve in the mouse (15–45 min) and the isolation and recording of neurons (approximately 1–3 h per recording). In addition, stimulation techniques, protocols to achieve single-fiber recordings, issues of data acquisition and action potential discrimination are discussed in detail. PMID:19180088

Duration of the distal compound muscle action potential for diagnosis of chronic inflammatory demyelinating polyneuropathy: effects of low-cut filters.

PubMed

Isose, Sagiri; Misawa, Sonoko; Sonoo, Masahiro; Shimuzu, Toshio; Oishi, Chizuko; Shibuya, Kazumoto; Nasu, Saiko; Sekiguchi, Yukari; Mitsuma, Satsuki; Beppu, Minako; Omori, Shigeki; Komori, Tetsuo; Kokubun, Norito; Inaba, Akira; Hirashima, Fumiko; Kuwabara, Satoshi

2014-10-01

In current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy, the cutoff values of distal compound muscle action potential (DCMAP) duration are defined using electromyogram low-cut filter setting of 20 Hz. We aimed to assess effects of low-cut filter on DCMAP duration (10 vs. 20 Hz). We prospectively measured DCMAP duration in 130 normal controls and 42 patients, fulfilling diagnostic criteria for typical chronic inflammatory demyelinating polyneuropathy by European Federation of Neurological Societies/Peripheral Nerve Society. Distal compound muscle action potential duration was significantly shortened with 20-Hz than 10-Hz filtering. When the cutoff values were defined as the upper limit of normal (ULN, mean + 2.5SD), the sensitivity/specificity was 67%/95% in 10-Hz recordings, and 69%/95% in 20-Hz recordings. This diagnostic accuracy was similar to that defined by receiver operating characteristic analyses. Distal compound muscle action potential duration significantly affected by the low-cut electromyogram filter setting, but with at least 10 and 20 Hz, the diagnostic accuracy is similar.

Human stem cell-derived cardiomyocytes detect drug-mediated changes in action potentials and ion currents.

PubMed

Gibson, John K; Yue, Yimei; Bronson, Jared; Palmer, Cassie; Numann, Randy

2014-01-01

It has been proposed that proarrhythmia assessment for safety pharmacology testing includes the use of human pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to detect drug-induced changes in cardiac electrophysiology. This study measured the actions of diverse agents on action potentials (AP) and ion currents recorded from hiPSC-CM. During AP experiments, the hiPSC-CM were paced at 1Hz during a baseline period, and when increasing concentrations of test compound were administered at 4-minute intervals. AP parameters, including duration (APD60 and APD90), resting membrane potential, rate of rise, and amplitude, were measured throughout the entire experiment. Voltage clamp experiments with E-4031 and nifedipine were similarly conducted. E-4031 produced a dose-dependent prolongation of cardiac action potential and blocked the hERG/IKr current with an IC50 of 17nM. At 3nM, dofetilide significantly increased APD90. Astemizole significantly increased APD60 and APD90 at 30nM. Terfenadine significantly increased APD90 at concentrations greater than 10nM. Fexofenadine, a metabolite of terfenadine, did not produce any electrophysiologic changes in cardiac action potentials. Flecainide produced a dose-dependent prolongation of the cardiac action potential at 1 and 3μM. Acute exposure to nifedipine significantly decreased APD60 and APD90 and produced a dose-dependent block of calcium current with an IC50 of 0.039μM. Verapamil first shortened APD60 and APD90 in a dose-dependent manner, until a compensating increase in APD90, presumably via hERG blockade, was observed at 1 and 3μM. Following a chronic exposure (20-24h) to clinically relevant levels of pentamidine, a significant increase in action potential duration was accompanied by early afterdepolarizations (EADs). These experiments show the ability of AP measured from hiPSC-CM to record the interactions of various ion channels via AP recording and avoid the limitations of using several single ion channel assays in a noncardiac tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

Feasibility Study of Utilization of Action Camera, GoPro Hero 4, Google Glass, and Panasonic HX-A100 in Spine Surgery.

PubMed

Lee, Chang Kyu; Kim, Youngjun; Lee, Nam; Kim, Byeongwoo; Kim, Doyoung; Yi, Seong

2017-02-15

Study for feasibility of commercially available action cameras in recording video of spine. Recent innovation of the wearable action camera with high-definition video recording enables surgeons to use camera in the operation at ease without high costs. The purpose of this study is to compare the feasibility, safety, and efficacy of commercially available action cameras in recording video of spine surgery. There are early reports of medical professionals using Google Glass throughout the hospital, Panasonic HX-A100 action camera, and GoPro. This study is the first report for spine surgery. Three commercially available cameras were tested: GoPro Hero 4 Silver, Google Glass, and Panasonic HX-A100 action camera. Typical spine surgery was selected for video recording; posterior lumbar laminectomy and fusion. Three cameras were used by one surgeon and video was recorded throughout the operation. The comparison was made on the perspective of human factor, specification, and video quality. The most convenient and lightweight device for wearing and holding throughout the long operation time was Google Glass. The image quality; all devices except Google Glass supported HD format and GoPro has unique 2.7K or 4K resolution. Quality of video resolution was best in GoPro. Field of view, GoPro can adjust point of interest, field of view according to the surgery. Narrow FOV option was the best for recording in GoPro to share the video clip. Google Glass has potentials by using application programs. Connectivity such as Wi-Fi and Bluetooth enables video streaming for audience, but only Google Glass has two-way communication feature in device. Action cameras have the potential to improve patient safety, operator comfort, and procedure efficiency in the field of spinal surgery and broadcasting a surgery with development of the device and applied program in the future. N/A.

On the Power Spectrum of Motor Unit Action Potential Trains Synchronized With Mechanical Vibration.

PubMed

Romano, Maria; Fratini, Antonio; Gargiulo, Gaetano D; Cesarelli, Mario; Iuppariello, Luigi; Bifulco, Paolo

2018-03-01

This study provides a definitive analysis of the spectrum of a motor unit action potential train (MUAPT) elicited by mechanical vibratory stimulation via a detailed and concise mathematical formulation. Experimental studies demonstrated that MUAPs are not exactly synchronized with the vibratory stimulus but show a variable latency jitter, whose effects have not been investigated yet. Synchronized action potential train was represented as a quasi-periodic sequence of a given MU waveform. The latency jitter of action potentials was modeled as a Gaussian stochastic process, in accordance to the previous experimental studies. A mathematical expression for power spectrum of a synchronized MUAPT has been derived. The spectrum comprises a significant continuous component and discrete components at the vibratory frequency and its harmonics. Their relevance is correlated to the level of synchronization: the weaker the synchronization the more relevant is the continuous spectrum. Electromyography (EMG) rectification enhances the discrete components. The derived equations have general validity and well describe the power spectrum of actual EMG recordings during vibratory stimulation. Results are obtained by appropriately setting the level of synchronization and vibration frequency. This paper definitively clarifies the nature of changes in spectrum of raw EMG recordings from muscles undergoing vibratory stimulation. Results confirm the need of motion artifact filtering for raw EMG recordings during stimulation and strongly suggest to avoid EMG rectification that significantly alters the spectrum characteristics.

Flexible graphene transistors for recording cell action potentials

NASA Astrophysics Data System (ADS)

Blaschke, Benno M.; Lottner, Martin; Drieschner, Simon; Bonaccini Calia, Andrea; Stoiber, Karolina; Rousseau, Lionel; Lissourges, Gaëlle; Garrido, Jose A.

2016-06-01

Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor’s transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

PubMed

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

The effect of recording site on extracted features of motor unit action potential.

PubMed

Artuğ, N Tuğrul; Goker, Imran; Bolat, Bülent; Osman, Onur; Kocasoy Orhan, Elif; Baslo, M Baris

2016-06-01

Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Enhanced functional expression of transient outward current in hypertrophied feline myocytes.

PubMed

Ten Eick, R E; Zhang, K; Harvey, R D; Bassett, A L

1993-08-01

Cardiac hypertrophy can decrease myocardial contractility and alter the electrophysiological activity of the heart. It is well documented that action potentials recorded from hypertrophied feline ventricular cells can exhibit depressed plateau voltages and prolonged durations. Similar findings have been made by others in rabbit, rat, guinea pig, and human heart. Whole-cell patch voltage-clamp studies designed to explain these changes in the action potential suggest that the only component of the membrane current recorded from feline right ventricular (RV) myocytes found to be substantially different from normal is the 4-amino-pyridine-sensitive transient outward current (I(to)). However, it was not clear if the change in I(to) could explain the changes in the action potential of hypertrophied cardiocytes, nor was it clear if these changes reflect an alteration in the electrophysiological character of the channels underlying I(to). A kinetic comparison of I(to) elicited by hypertrophied RV myocytes with that elicited by comparable normal RV myocytes previously revealed no differences, suggesting that the increased magnitude of the peak I(to) recorded from hypertrophied myocytes arises because the current density increases and not because of any alteration in the kinetic parameters governing the current. This finding suggests that in hypertrophy additional normal channels are expressed rather than a kinetically different channel subtype emerging. Investigations designed to determine if enhancement of I(to) could explain the hypertrophy-induced changes in plateau voltage and action potential duration suggest that a change in I(to) density can indeed explain the entire effect of hypertrophy on RV action potentials. If this notion is correct, the likelihood of "sudden death" in patients with myocardial hypertrophy might be decreased by a blocker selective for cardiac I(to).

A Novel Stimulus Artifact Removal Technique for High-Rate Electrical Stimulation

PubMed Central

Heffer, Leon F; Fallon, James B

2008-01-01

Electrical stimulus artifact corrupting electrophysiological recordings often make the subsequent analysis of the underlying neural response difficult. This is particularly evident when investigating short-latency neural activity in response to high-rate electrical stimulation. We developed and evaluated an off-line technique for the removal of stimulus artifact from electrophysiological recordings. Pulsatile electrical stimulation was presented at rates of up to 5000 pulses/s during extracellular recordings of guinea pig auditory nerve fibers. Stimulus artifact was removed by replacing the sample points at each stimulus artifact event with values interpolated along a straight line, computed from neighbouring sample points. This technique required only that artifact events be identifiable and that the artifact duration remained less than both the inter-stimulus interval and the time course of the action potential. We have demonstrated that this computationally efficient sample-and-interpolate technique removes the stimulus artifact with minimal distortion of the action potential waveform. We suggest that this technique may have potential applications in a range of electrophysiological recording systems. PMID:18339428

An automated system using spatial oversampling for optical mapping in murine atria. Development and validation with monophasic and transmembrane action potentials.

PubMed

Yu, Ting Yue; Syeda, Fahima; Holmes, Andrew P; Osborne, Benjamin; Dehghani, Hamid; Brain, Keith L; Kirchhof, Paulus; Fabritz, Larissa

2014-08-01

We developed and validated a new optical mapping system for quantification of electrical activation and repolarisation in murine atria. The system makes use of a novel 2nd generation complementary metal-oxide-semiconductor (CMOS) camera with deliberate oversampling to allow both assessment of electrical activation with high spatial and temporal resolution (128 × 2048 pixels) and reliable assessment of atrial murine repolarisation using post-processing of signals. Optical recordings were taken from isolated, superfused and electrically stimulated murine left atria. The system reliably describes activation sequences, identifies areas of functional block, and allows quantification of conduction velocities and vectors. Furthermore, the system records murine atrial action potentials with comparable duration to both monophasic and transmembrane action potentials in murine atria. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

Use of sensory and motor action potentials to identify the position of trigeminal nerve divisions for radiofrequency thermocoagulation.

PubMed

Lin, Bo; Lu, Xuguang; Zhai, Xinli; Cai, Zhigang

2014-12-01

The objective of this study was to develop an electrophysiological method for intraoperative localization of the trigeminal nerve branches during radiofrequency thermocoagulation (RFTC). Twenty-three patients who were scheduled to undergo RFTC were included. The trigeminal nerve root was stimulated through the foramen ovale using the radiofrequency cannula. Antidromic responses were recorded from the target division through supraorbital, infraorbital, and mental foramina electrodes, and an additional electrode at the masseter muscle. Sensory and motor action responses, as well as verbal and masseter contraction responses, were recorded and correlated. The antidromic responses were easily recorded in the target division in all 23 patients, and they were invariably correlated with the patient's verbal responses. The potentials were recorded successively from V1 to V3. The amplitude in each division before and after RFTC showed little difference in response to electrical stimulation with the same current. The motor trigeminal nerve action potentials were recorded in 10 patients; 7 of these patients had postoperative masseter muscle weakness, while the remaining 3 had normal masseter muscle function. Potentials with low amplitudes were usually obtained from neighboring divisions, but no unexpected denervation of any branches was observed. All the patients experienced immediate pain relief after the procedure. This technique is sensitive and easy to apply. The sensory and motor potentials matched the verbal responses and the complications. Although it cannot completely substitute for the patient's verbal response, this approach is helpful in uncooperative patients, and it predicts and reduces the incidence of masseter muscle weakness. The use of these complementary techniques could increase the chances of treatment success.

Synchronization of action potentials during low-magnesium-induced bursting

PubMed Central

Johnson, Sarah E.; Hudson, John L.

2015-01-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg2+ model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg2+. In decreased Mg2+ medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg2+ media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg2+ concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. PMID:25609103

Synchronization of action potentials during low-magnesium-induced bursting.

PubMed

Johnson, Sarah E; Hudson, John L; Kapur, Jaideep

2015-04-01

The relationship between mono- and polysynaptic strength and action potential synchronization was explored using a reduced external Mg(2+) model. Single and dual whole cell patch-clamp recordings were performed in hippocampal cultures in three concentrations of external Mg(2+). In decreased Mg(2+) medium, the individual cells transitioned to spontaneous bursting behavior. In lowered Mg(2+) media the larger excitatory synaptic events were observed more frequently and fewer transmission failures occurred, suggesting strengthened synaptic transmission. The event synchronization was calculated for the neural action potentials of the cell pairs, and it increased in media where Mg(2+) concentration was lowered. Analysis of surrogate data where bursting was present, but no direct or indirect connections existed between the neurons, showed minimal action potential synchronization. This suggests the synchronization of action potentials is a product of the strengthening synaptic connections within neuronal networks. Copyright © 2015 the American Physiological Society.

Action potential propagation recorded from single axonal arbors using multi-electrode arrays.

PubMed

Tovar, Kenneth R; Bridges, Daniel C; Wu, Bian; Randall, Connor; Audouard, Morgane; Jang, Jiwon; Hansma, Paul K; Kosik, Kenneth S

2018-04-11

We report the presence of co-occurring extracellular action potentials (eAPs) from cultured mouse hippocampal neurons among groups of planar electrodes on multi-electrode arrays (MEAs). The invariant sequences of eAPs among co-active electrode groups, repeated co-occurrences and short inter-electrode latencies are consistent with action potential propagation in unmyelinated axons. Repeated eAP co-detection by multiple electrodes was widespread in all our data records. Co-detection of eAPs confirms they result from the same neuron and allows these eAPs to be isolated from all other spikes independently of spike sorting algorithms. We averaged co-occurring events and revealed additional electrodes with eAPs that would otherwise be below detection threshold. We used these eAP cohorts to explore the temperature sensitivity of action potential propagation and the relationship between voltage-gated sodium channel density and propagation velocity. The sequence of eAPs among co-active electrodes 'fingerprints' neurons giving rise to these events and identifies them within neuronal ensembles. We used this property and the non-invasive nature of extracellular recording to monitor changes in excitability at multiple points in single axonal arbors simultaneously over several hours, demonstrating independence of axonal segments. Over several weeks, we recorded changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. Our work illustrates how repeated eAP co-occurrences can be used to extract physiological data from single axons with low electrode density MEAs. However, repeated eAP co-occurrences leads to over-sampling spikes from single neurons and thus can confound traditional spike-train analysis.

Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

PubMed

Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

2011-06-08

ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

PubMed Central

Muñoz, Fabián; Fuentealba, Pablo

2012-01-01

Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold. PMID:22279567

Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

PubMed Central

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

2012-01-01

BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

PubMed

Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

2012-10-01

Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor.

PubMed

Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M

2011-12-18

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.

Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

NASA Astrophysics Data System (ADS)

Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

2012-03-01

The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be recorded, thus showing that a stable and tight seal forms between the nanotube and cell membrane. We also show that multiple BIT-FETs can record multiplexed intracellular signals from both single cells and networks of cells.

Na+ current in presynaptic terminals of the crayfish opener cannot initiate action potentials.

PubMed

Lin, Jen-Wei

2016-01-01

Action potential (AP) propagation in presynaptic axons of the crayfish opener neuromuscular junction (NMJ) was investigated by simultaneously recording from a terminal varicosity and a proximal branch. Although orthodromically conducting APs could be recorded in terminals with amplitudes up to 70 mV, depolarizing steps in terminals to -20 mV or higher failed to fire APs. Patch-clamp recordings did detect Na(+) current (INa) in most terminals. The INa exhibited a high threshold and fast activation rate. Local perfusion of Na(+)-free saline showed that terminal INa contributed to AP waveform by slightly accelerating the rising phase and increasing the peak amplitude. These findings suggest that terminal INa functions to "touch up" but not to generate APs. Copyright © 2016 the American Physiological Society.

Multi-electrode array technologies for neuroscience and cardiology

NASA Astrophysics Data System (ADS)

Spira, Micha E.; Hai, Aviad

2013-02-01

At present, the prime methodology for studying neuronal circuit-connectivity, physiology and pathology under in vitro or in vivo conditions is by using substrate-integrated microelectrode arrays. Although this methodology permits simultaneous, cell-non-invasive, long-term recordings of extracellular field potentials generated by action potentials, it is 'blind' to subthreshold synaptic potentials generated by single cells. On the other hand, intracellular recordings of the full electrophysiological repertoire (subthreshold synaptic potentials, membrane oscillations and action potentials) are, at present, obtained only by sharp or patch microelectrodes. These, however, are limited to single cells at a time and for short durations. Recently a number of laboratories began to merge the advantages of extracellular microelectrode arrays and intracellular microelectrodes. This Review describes the novel approaches, identifying their strengths and limitations from the point of view of the end users -- with the intention to help steer the bioengineering efforts towards the needs of brain-circuit research.

Multi-electrode array technologies for neuroscience and cardiology.

PubMed

Spira, Micha E; Hai, Aviad

2013-02-01

At present, the prime methodology for studying neuronal circuit-connectivity, physiology and pathology under in vitro or in vivo conditions is by using substrate-integrated microelectrode arrays. Although this methodology permits simultaneous, cell-non-invasive, long-term recordings of extracellular field potentials generated by action potentials, it is 'blind' to subthreshold synaptic potentials generated by single cells. On the other hand, intracellular recordings of the full electrophysiological repertoire (subthreshold synaptic potentials, membrane oscillations and action potentials) are, at present, obtained only by sharp or patch microelectrodes. These, however, are limited to single cells at a time and for short durations. Recently a number of laboratories began to merge the advantages of extracellular microelectrode arrays and intracellular microelectrodes. This Review describes the novel approaches, identifying their strengths and limitations from the point of view of the end users--with the intention to help steer the bioengineering efforts towards the needs of brain-circuit research.

Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

PubMed

Ahmed, Zaghloul; Wieraszko, Andrzej

2015-07-01

This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed. © 2015 Wiley Periodicals, Inc.

Spikes, Local Field Potentials, and Electrocorticogram Characterization during Motor Learning in Rats for Brain Machine Interface Tasks.

PubMed

Marzullo, T C; Dudley, J R; Miller, C R; Trejo, L; Kipke, D R

2005-01-01

Brain machine interface development typically falls into two arenas, invasive extracellular recording and non-invasive electroencephalogram recording methods. The relationship between action potentials and field potentials is not well understood, and investigation of interrelationships may improve design of neuroprosthetic control systems. Rats were trained on a motor learning task whereby they had to insert their noses into an aperture while simultaneously pressing down on levers with their forepaws; spikes, local field potentials (LFPs), and electrocorticograms (ECoGs) over the motor cortex were recorded and characterized. Preliminary results suggest that the LFP activity in lower cortical layers oscillates with the ECoG.

Short- and long-term functional plasticity of white matter induced by oligodendrocyte depolarization in the hippocampus.

PubMed

Yamazaki, Yoshihiko; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Xu, Ming; Ikenaka, Kazuhiro; Fujii, Satoshi; Tanaka, Kenji F

2014-08-01

Plastic changes in white matter have received considerable attention in relation to normal cognitive function and learning. Oligodendrocytes and myelin, which constitute the white matter in the central nervous system, can respond to neuronal activity with prolonged depolarization of membrane potential and/or an increase in the intracellular Ca(2+) concentration. Depolarization of oligodendrocytes increases the conduction velocity of an action potential along axons myelinated by the depolarized oligodendrocytes, indicating that white matter shows functional plasticity, as well as structural plasticity. However, the properties and mechanism of oligodendrocyte depolarization-induced functional plastic changes in white matter are largely unknown. Here, we investigated the functional plasticity of white matter in the hippocampus using mice with oligodendrocytes expressing channelrhodopsin-2. Using extracellular recordings of compound action potentials at the alveus of the hippocampus, we demonstrated that light-evoked depolarization of oligodendrocytes induced early- and late-onset facilitation of axonal conduction that was dependent on the magnitude of oligodendrocyte depolarization; the former lasted for approximately 10 min, whereas the latter continued for up to 3 h. Using whole-cell recordings from CA1 pyramidal cells and recordings of antidromic action potentials, we found that the early-onset short-lasting component included the synchronization of action potentials. Moreover, pharmacological analysis demonstrated that the activation of Ba(2+) -sensitive K(+) channels was involved in early- and late-onset facilitation, whereas 4-aminopyridine-sensitive K(+) channels were only involved in the early-onset component. These results demonstrate that oligodendrocyte depolarization induces short- and long-term functional plastic changes in the white matter of the hippocampus and plays active roles in brain functions. © 2014 Wiley Periodicals, Inc.

Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics

PubMed Central

Yu, Yuguo; Shu, Yousheng; McCormick, David A.

2008-01-01

Neocortical action potential responses in vivo are characterized by considerable threshold variability, and thus timing and rate variability, even under seemingly identical conditions. This finding suggests that cortical ensembles are required for accurate sensorimotor integration and processing. Intracellularly, trial-to-trial variability results not only from variation in synaptic activities, but also in the transformation of these into patterns of action potentials. Through simultaneous axonal and somatic recordings and computational simulations, we demonstrate that the initiation of action potentials in the axon initial segment followed by backpropagation of these spikes throughout the neuron results in a distortion of the relationship between the timing of synaptic and action potential events. In addition, this backpropagation also results in an unusually high rate of rise of membrane potential at the foot of the action potential. The distortion of the relationship between the amplitude time course of synaptic inputs and action potential output caused by spike back-propagation results in the appearance of high spike threshold variability at the level of the soma. At the point of spike initiation, the axon initial segment, threshold variability is considerably less. Our results indicate that spike generation in cortical neurons is largely as expected by Hodgkin—Huxley theory and is more precise than previously thought. PMID:18632930

Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge.

PubMed

Michel, K; Michaelis, M; Mazzuoli, G; Mueller, K; Vanden Berghe, P; Schemann, M

2011-12-15

Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (≥200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by -conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores.

Pb2+ Modulates Ca2+ Membrane Permeability In Paramecium

NASA Astrophysics Data System (ADS)

Bernal-Martínez, Juan; Ortega Soto, Arturo

2004-09-01

Intracellular recording experiments in current clamp configuration were done to evaluate whether Pb2+ modulates ionic membrane permeability in the fresh water Paramecium tetraurelia. It was found that Pb2+ triggers in a dose-dependent manner, a burst of spontaneous action potentials followed by a robust and sustained after hyper-polarization. In addition, Pb2+ increased the frequency of firing the spontaneous Ca2+-Action Potential and also, the duration of Ca2+-Action Potential, in a dose and reversibly-dependent manner. These results suggest that Pb2+ increases calcium membrane permeability of Paramecium and probably activates a calcium-dependent-potassium conductance in the ciliate.

Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

PubMed

Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

2017-09-01

Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

Human Neck Response during Vertical Impact with Variable Weighted Helmets

DTIC Science & Technology

2006-09-01

activated, action potentials from the brain travel to motor neurons which branch out to the muscle fibers . EMG sensors record the action potentials of...the motor unit, comprised of several activated muscle fibers . An "EMG signal directly reflects the recruitment and firing characteristics of the...upper trapezius and SCM associated with isometric muscle contractions. They thoroughly investigated the mechanics of muscle fatigue during helmet loading

LFPy: a tool for biophysical simulation of extracellular potentials generated by detailed model neurons.

PubMed

Lindén, Henrik; Hagen, Espen; Lęski, Szymon; Norheim, Eivind S; Pettersen, Klas H; Einevoll, Gaute T

2013-01-01

Electrical extracellular recordings, i.e., recordings of the electrical potentials in the extracellular medium between cells, have been a main work-horse in electrophysiology for almost a century. The high-frequency part of the signal (≳500 Hz), i.e., the multi-unit activity (MUA), contains information about the firing of action potentials in surrounding neurons, while the low-frequency part, the local field potential (LFP), contains information about how these neurons integrate synaptic inputs. As the recorded extracellular signals arise from multiple neural processes, their interpretation is typically ambiguous and difficult. Fortunately, a precise biophysical modeling scheme linking activity at the cellular level and the recorded signal has been established: the extracellular potential can be calculated as a weighted sum of all transmembrane currents in all cells located in the vicinity of the electrode. This computational scheme can considerably aid the modeling and analysis of MUA and LFP signals. Here, we describe LFPy, an open source Python package for numerical simulations of extracellular potentials. LFPy consists of a set of easy-to-use classes for defining cells, synapses and recording electrodes as Python objects, implementing this biophysical modeling scheme. It runs on top of the widely used NEURON simulation environment, which allows for flexible usage of both new and existing cell models. Further, calculation of extracellular potentials using the line-source-method is efficiently implemented. We describe the theoretical framework underlying the extracellular potential calculations and illustrate by examples how LFPy can be used both for simulating LFPs, i.e., synaptic contributions from single cells as well a populations of cells, and MUAs, i.e., extracellular signatures of action potentials.

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

PubMed

Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

2018-01-01

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand.

Injury risk associated with playing actions during competitive soccer

PubMed Central

Rahnama, N; Reilly, T; Lees, A

2002-01-01

Objective: To assess the exposure of players to injury risk during English Premier League soccer matches in relation to selected factors. Methods: Injury risk was assessed by rating the injury potential of playing actions during competition with respect to (a) type of playing action, (b) period of the game, (c) zone of the pitch, and (d) playing either at home or away. In all, 10 games from the English Premier League 1999–2000 were chosen for analysis. A notation system was used whereby 16 soccer specific playing actions were classified into three categories: those inducing actual injury, those with a potential for injury (graded as mild, moderate, or high), and those deemed to have no potential for injury. The pitch was divided into 18 zones, and the position of each event was recorded along with time elapsed in the game, enabling six 15 minute periods to be defined. Results: Close to 18 000 actions were notated. On average (mean (SD)), 1788 (73) events (one every three seconds), 767 (99) events with injury potential (one every six seconds), and 2 (1) injuries (one every 45 minutes) per game were recorded. An overall injury incidence of 53 per 1000 playing hours was calculated. Receiving a tackle, receiving a "charge", and making a tackle were categorised as having a substantial injury risk, and goal catch, goal punch, kicking the ball, shot on goal, set kick, and heading the ball were all categorised as having a significant injury risk. All other actions were deemed low in risk. The first 15 minutes of each half contained the highest number of actions with mild injury potential, the last 15 minutes having the highest number of actions with moderate injury potential (p<0.01). The first and last 15 minutes of the game had the highest number of actions with high injury potential, although not significant. More actions with mild injury potential occurred in the goal area, and more actions with moderate and high injury potential occurred in the zone adjacent to the goal area (p<0.001). There was no significant difference between home and away with regard to injury potential. Conclusions: Playing actions with high injury risk were linked to contesting possession. Injury risk was highest in the first and last 15 minutes of the game, reflecting the intense engagements in the opening period and the possible effect of fatigue in the closing period. Injury risk was concentrated in the areas of the pitch where possession of the ball is most vigorously contested, which were specific attacking and defending zones close to the goal. Injury potential was no greater in away matches than at home. PMID:12351333

Superfund record of decision (EPA region 10): Idaho National Engineering Lab, (USDOE) Operable Unit 26 (Stationary Low-Power Reactor-1 and Boiling Water Reactor Experiment-I Burial Grounds), Idaho Falls, ID, December 1, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1997-03-01

This document presents the selected remedial action for the Stationary Low-Power Reactor-1 (SL-1) burial ground, the Boiling Water Reactor Experiment-I (BORAX-I) burial ground, and 10 no action sites in Waste Area Group 5. Actual or threatened releases of hazardous substances from the SL-1 and BORAX-I burial grounds, if not addressed by implementing the response action selected in this Record of Decision, may present a current or potential threat to public health, welfare, or the environment. The 10 no action sites do not present a threat to human health or the environment.

Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

PubMed Central

Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

2014-01-01

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies. PMID:24917788

Crossed motor innervation of the base of human tongue

PubMed Central

Jordan, Amy S.; Nicholas, Christian L.; Cori, Jennifer M.; Semmler, John G.; Trinder, John

2015-01-01

Muscle fibers of the genioglossus (GG) form the bulk of the muscle mass at the base of the tongue. The motor control of the tongue is critical for vocalization, feeding, and breathing. Our goal was to assess the patterns of motor innervation of GG single motor units (SMUs) in humans. Simultaneous monopolar recordings were obtained from four sites in the base of the tongue bilaterally at two antero-posterior levels from 16 resting, awake, healthy adult males, who wore a face mask with airway pressure and airflow sensors. We analyzed 69 data segments in which at least one lead contained large action potentials generated by an SMU. Such potentials served as triggers for spike-triggered averaging (STA) of signals recorded from the other three sites. Spontaneous activity of the SMUs was classified as inspiratory modulated, expiratory modulated, or tonic. Consistent with the antero-posterior orientation of GG fibers, 44 STAs (77%) recorded ipsilateral to the trigger yielded sharp action potentials with a median amplitude of 52 μV [interquartile range (IQR): 25–190] that were time shifted relative to the trigger by about 1 ms. Notably, 48% of recordings on the side opposite to the trigger also yielded sharp action potentials. Of those, 17 (29%) had a median amplitude of 63 μV (IQR: 39–96), and most were generated by tonic SMUs. Thus a considerable proportion of GG muscle fibers receive a crossed motor innervation. Crossed innervation may help ensure symmetry and stability of tongue position and movements under normal conditions and following injury or degenerative changes affecting the tongue. PMID:25855691

Membrane potential dynamics of axons in cultured hippocampal neurons probed by second-harmonic-generation imaging

NASA Astrophysics Data System (ADS)

Nuriya, Mutsuo; Yasui, Masato

2010-03-01

The electrical properties of axons critically influence the nature of communication between neurons. However, due to their small size, direct measurement of membrane potential dynamics in intact and complex mammalian axons has been a challenge. Furthermore, quantitative optical measurements of axonal membrane potential dynamics have not been available. To characterize the basic principles of somatic voltage signal propagation in intact axonal arbors, second-harmonic-generation (SHG) imaging is applied to cultured mouse hippocampal neurons. When FM4-64 is applied extracellularly to dissociated neurons, whole axonal arbors are visualized by SHG imaging. Upon action potential generation by somatic current injection, nonattenuating action potentials are recorded in intact axonal arbors. Interestingly, however, both current- and voltage-clamp recordings suggest that nonregenerative subthreshold somatic voltage changes at the soma are poorly conveyed to these axonal sites. These results reveal the nature of membrane potential dynamics of cultured hippocampal neurons, and further show the possibility of SHG imaging in physiological investigations of axons.

Intracellular and Extracellular Recording of Spontaneous Action Potentials in Mammalian Neurons and Cardiac Cells with 3D Plasmonic Nanoelectrodes.

PubMed

Dipalo, Michele; Amin, Hayder; Lovato, Laura; Moia, Fabio; Caprettini, Valeria; Messina, Gabriele C; Tantussi, Francesco; Berdondini, Luca; De Angelis, Francesco

2017-06-14

Three-dimensional vertical micro- and nanostructures can enhance the signal quality of multielectrode arrays and promise to become the prime methodology for the investigation of large networks of electrogenic cells. So far, access to the intracellular environment has been obtained via spontaneous poration, electroporation, or by surface functionalization of the micro/nanostructures; however, these methods still suffer from some limitations due to their intrinsic characteristics that limit their widespread use. Here, we demonstrate the ability to continuously record both extracellular and intracellular-like action potentials at each electrode site in spontaneously active mammalian neurons and HL-1 cardiac-derived cells via the combination of vertical nanoelectrodes with plasmonic optoporation. We demonstrate long-term and stable recordings with a very good signal-to-noise ratio. Additionally, plasmonic optoporation does not perturb the spontaneous electrical activity; it permits continuous recording even during the poration process and can regulate extracellular and intracellular contributions by means of partial cellular poration.

The influence of passband limitation on the waveform of extracellular action potential.

PubMed

Mizuhiki, Takashi; Inaba, Kiyonori; Setogawa, Tsuyoshi; Toda, Koji; Ozaki, Shigeru; Shidara, Muneteka

2012-03-01

The duration of the extracellular action potential (EAP) in single neuronal recording has often been used as a clue to infer biochemical, physiological or functional substrate of the recorded neurons, e.g. neurochemical type. However, when recording a neuronal activity, the high-pass filter is routinely used to achieve higher signal-to-noise ratio. Signal processing theory predicts that passband limitation stretches the waveform of discrete brief impulse. To examine whether the duration of filtered EAP could be the reliable measure, we investigated the influence of high-pass filter both by simulation and unfiltered unit recording data from monkey dorsal raphe. Consistent with the findings in recent theoretical study, the unfiltered EAPs displayed the sharp wave without following bumps. The duration of unfiltered EAP was not correlated with that of filtered EAP. Thus the duration of original EAP cannot be estimated from filtered EAP. It is needed to reexamine the EAP duration measured for classifying the neurons whose activities were recorded under the passband limitation in the related studies. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

An oscilloscope spot intensifier, to improve photographic recordings of action potentials.

PubMed

Evans, M H

1985-06-01

A circuit diagram is shown for a semiconductor device to intensify the brightness of an oscilloscope during the rapidly rising and falling phases of signals such as action potentials. Brightening pulses proportional in amplitude to the rate of change in the Y-axis are available for connection to an oscilloscope with an external intensity ('Z') modulation input. The circuit requires one transistor, one dual operational amplifier and two single fast operational amplifiers.

Cardiac action potential imaging

NASA Astrophysics Data System (ADS)

Tian, Qinghai; Lipp, Peter; Kaestner, Lars

2013-06-01

Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

The monophasic action potential upstroke: a means of characterizing local conduction.

PubMed

Levine, J H; Moore, E N; Kadish, A H; Guarnieri, T; Spear, J F

1986-11-01

The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.

Variability of acute extracellular action potential measurements with multisite silicon probes

PubMed Central

Scott, Kimberly M.; Du, Jiangang; Lester, Henry A.; Masmanidis, Sotiris C.

2012-01-01

Device miniaturization technologies have led to significant advances in sensors for extracellular measurements of electrical activity in the brain. Multisite, silicon-based probes containing implantable electrode arrays afford greater coverage of neuronal activity than single electrodes and therefore potentially offer a more complete view of how neuronal ensembles encode information. However, scaling up the number of sites is not sufficient to ensure capture of multiple neurons, as action potential signals from extracellular electrodes may vary due to numerous factors. In order to understand the large-scale recording capabilities and potential limitations of multisite probes, it is important to quantify this variability, and to determine whether certain key device parameters influence the recordings. Here we investigate the effect of four parameters, namely, electrode surface, width of the structural support shafts, shaft number, and position of the recording site relative to the shaft tip. This study employs acutely implanted silicon probes containing up to 64 recording sites, whose performance is evaluated by the metrics of noise, spike amplitude, and spike detection probability. On average, we find no significant effect of device geometry on spike amplitude and detection probability but we find significant differences among individual experiments, with the likelihood of detecting spikes varying by a factor of approximately three across trials. PMID:22971352

Voltage-sensitive dye recording from networks of cultured neurons

NASA Astrophysics Data System (ADS)

Chien, Chi-Bin

This thesis describes the development and testing of a sensitive apparatus for recording electrical activity from microcultures of rat superior cervical ganglion (SCG) neurons by using voltage-sensitive fluorescent dyes.The apparatus comprises a feedback-regulated mercury arc light source, an inverted epifluorescence microscope, a novel fiber-optic camera with discrete photodiode detectors, and low-noise preamplifiers. Using an NA 0.75 objective and illuminating at 10 W/cm2 with the 546 nm mercury line, a typical SCG neuron stained with the styryl dye RH423 gives a detected photocurrent of 1 nA; the light source and optical detectors are quiet enough that the shot noise in this photocurrent--about.03% rms--dominates. The design, theory, and performance of this dye-recording apparatus are discussed in detail.Styryl dyes such as RH423 typically give signals of 1%/100 mV on these cells; the signals are linear in membrane potential, but do not appear to arise from a purely electrochromic mechanism. Given this voltage sensitivity and the noise level of the apparatus, it should be possible to detect both action potentials and subthreshold synaptic potentials from SCG cell bodies. In practice, dye recording can easily detect action potentials from every neuron in an SCG microculture, but small synaptic potentials are obscured by dye signals from the dense network of axons.In another microculture system that does not have such long and complex axons, this dye-recording apparatus should be able to detect synaptic potentials, making it possible to noninvasively map the synaptic connections in a microculture, and thus to study long-term synaptic plasticity.

Tracking individual action potentials throughout mammalian axonal arbors.

PubMed

Radivojevic, Milos; Franke, Felix; Altermatt, Michael; Müller, Jan; Hierlemann, Andreas; Bakkum, Douglas J

2017-10-09

Axons are neuronal processes specialized for conduction of action potentials (APs). The timing and temporal precision of APs when they reach each of the synapses are fundamentally important for information processing in the brain. Due to small diameters of axons, direct recording of single AP transmission is challenging. Consequently, most knowledge about axonal conductance derives from modeling studies or indirect measurements. We demonstrate a method to noninvasively and directly record individual APs propagating along millimeter-length axonal arbors in cortical cultures with hundreds of microelectrodes at microsecond temporal resolution. We find that cortical axons conduct single APs with high temporal precision (~100 µs arrival time jitter per mm length) and reliability: in more than 8,000,000 recorded APs, we did not observe any conduction or branch-point failures. Upon high-frequency stimulation at 100 Hz, successive became slower, and their arrival time precision decreased by 20% and 12% for the 100th AP, respectively.

What Is a Personal Health Record (PHR)?

MedlinePlus

... and critical step in the evolution of health information management ( HIM ). The book “ The Personal Health Record ” assists ... potential health conditions, treatment options, costs of treatment, management of chronic conditions, healthy lifestyle choices, preventive actions, and monitoring the ... Does a PHR Work? How Does a ...

Contribution of the Axon Initial Segment to Action Potentials Recorded Extracellularly.

PubMed

Teleńczuk, Maria; Brette, Romain; Destexhe, Alain; Teleńczuk, Bartosz

2018-01-01

Action potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at the onset of an AP the soma and the AIS form a dipole. We study the extracellular signature [the extracellular AP (EAP)] generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. The soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic extracellular potentials recorded in the brain.

Who needs a referee? How incorrect basketball actions are automatically detected by basketball players' brain

PubMed Central

Proverbio, Alice Mado; Crotti, Nicola; Manfredi, Mirella; Adorni, Roberta; Zani, Alberto

2012-01-01

While the existence of a mirror neuron system (MNS) representing and mirroring simple purposeful actions (such as reaching) is known, neural mechanisms underlying the representation of complex actions (such as ballet, fencing, etc.) that are learned by imitation and exercise are not well understood. In this study, correct and incorrect basketball actions were visually presented to professional basketball players and naïve viewers while their EEG was recorded. The participants had to respond to rare targets (unanimated scenes). No category or group differences were found at perceptual level, ruling out the possibility that correct actions might be more visually familiar. Large, anterior N400 responses of event-related brain potentials to incorrectly performed basketball actions were recorded in skilled brains only. The swLORETA inverse solution for incorrect–correct contrast showed that the automatic detection of action ineffectiveness/incorrectness involved the fronto/parietal MNS, the cerebellum, the extra-striate body area, and the superior temporal sulcus. PMID:23181191

Low concentrations of procaine and diethylaminoethanol reduce the excitability but not the action potential amplitude of hippocampal pyramidal cells.

PubMed

Butterworth, J F; Cole, L R

1990-10-01

To determine whether concentrations of diethylaminoethanol (DEAE) and procaine below those that reduce the amplitude of action potentials might alter the excitability of brain cells, a single microelectrode intracellular recording technique was used to measure firing threshold and action potential amplitude of pyramidal cells in rat hippocampal slices. At low concentrations of both DEAE (less than or equal to 5 mM) and procaine (less than or equal to 0.5 mM), firing threshold was significantly increased (P less than 0.01), whereas action potential spike amplitude was minimally altered. At higher concentrations, both drugs significantly decreased action potential spike amplitude (P less than 0.025) as well as increased firing threshold (P less than 0.001). Diethylaminoethanol tended to increase threshold relatively more than procaine, when drug concentrations that similarly reduced action potential amplitude were compared. All actions of DEAE and procaine were reversible. Inhibition of action potentials by DEAE and procaine was clearly concentration-dependent (P less than or equal to 0.015). Diethylaminoethanol effects on threshold were marginally concentration-dependent (P = 0.08); procaine did not demonstrate clear concentration-dependent effects (P = 0.33) over the concentrations tested in this study. These similar actions of procaine and DEAE on brain cells suggest a mechanism by which intravenous local anesthetics may contribute to the general anesthetic state. Moreover, it appears possible that procaine metabolism and DEAE accumulation may underlie the prolonged effects sometimes seen after intravenous procaine administration.

A neuronal mechanism of propofol-induced central respiratory depression in newborn rats.

PubMed

Kashiwagi, Masanori; Okada, Yasumasa; Kuwana, Shun-Ichi; Sakuraba, Shigeki; Ochiai, Ryoichi; Takeda, Junzo

2004-07-01

The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.

Physiological recordings and RNA sequencing of the gustatory appendages of the yellow-fever mosquito Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Electrophysiological recording of action potentials from sensory neurons of mosquitoes provides investigators a glimpse into the chemical perception of these disease vectors. We have recently identified a bitter sensing neuron in the labellum of female Aedes aegypti that responds to DEET and other ...

Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

PubMed

Homma, S; Nakajima, Y; Hayashi, K; Toma, S

1986-01-01

Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

Corticospinal Excitability during the Observation of Social Behavior

ERIC Educational Resources Information Center

Bucchioni, Giulia; Cavallo, Andrea; Ippolito, Davide; Marton, Gianluca; Castiello, Umberto

2013-01-01

Evidence suggests that the observation of an action induces in the observers an enhancement of motor evoked potentials (MEPs) recorded by the observer's muscles corresponding to those involved in the observed action. Although this is a well-studied phenomenon, it remains still unclear how the viewer's motor facilitation is influenced by the social…

Myelin Loss and Axonal Ion Channel Adaptations Associated with Gray Matter Neuronal Hyperexcitability

PubMed Central

Hamada, Mustafa S.

2015-01-01

Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that βIV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, βIV-spectrin, and the ion channel expression were maintained. Structure–function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons. PMID:25948275

Upper stimulation threshold for retinal ganglion cell activation.

PubMed

Meng, Kevin; Fellner, Andreas; Rattay, Frank; Ghezzi, Diego; Meffin, Hamish; Ibbotson, Michael R; Kameneva, Tatiana

2018-08-01

The existence of an upper threshold in electrically stimulated retinal ganglion cells (RGCs) is of interest because of its relevance to the development of visual prosthetic devices, which are designed to restore partial sight to blind patients. The upper threshold is defined as the stimulation level above which no action potentials (direct spikes) can be elicited in electrically stimulated retina. We collected and analyzed in vitro recordings from rat RGCs in response to extracellular biphasic (anodic-cathodic) pulse stimulation of varying amplitudes and pulse durations. Such responses were also simulated using a multicompartment model. We identified the individual cell variability in response to stimulation and the phenomenon known as upper threshold in all but one of the recorded cells (n  =  20/21). We found that the latencies of spike responses relative to stimulus amplitude had a characteristic U-shape. In silico, we showed that the upper threshold phenomenon was observed only in the soma. For all tested biphasic pulse durations, electrode positions, and pulse amplitudes above lower threshold, a propagating action potential was observed in the distal axon. For amplitudes above the somatic upper threshold, the axonal action potential back-propagated in the direction of the soma, but the soma's low level of hyperpolarization prevented action potential generation in the soma itself. An upper threshold observed in the soma does not prevent spike conductance in the axon.

A physical action potential generator: design, implementation and evaluation.

PubMed

Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

2015-01-01

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury

DTIC Science & Technology

2013-05-14

enzymes . At sufficiently high doses of glutamate, this process culminates in excitogenic cell death [1]. Treatments to mitigate neuronal damage during...To evaluate the potential for therapeutic screening, we assessed the effect of several small molecule antagonists on excitotoxicity in a moderate...C. Current clamp recordings showing repeated overshooting action potentials are evoked by injection of a 75 pA current. D. Voltage-clamp recordings

Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate.

PubMed

Tyzio, Roman; Allene, Camille; Nardou, Romain; Picardo, Michel A; Yamamoto, Sumii; Sivakumaran, Sudhir; Caiati, Maddalena D; Rheims, Sylvain; Minlebaev, Marat; Milh, Mathieu; Ferré, Pascal; Khazipov, Rustem; Romette, Jean-Louis; Lorquin, Jean; Cossart, Rosa; Khalilov, Ilgam; Nehlig, Astrid; Cherubini, Enrico; Ben-Ari, Yehezkel

2011-01-05

GABA depolarizes immature neurons because of a high [Cl(-)](i) and orchestrates giant depolarizing potential (GDP) generation. Zilberter and coworkers (Rheims et al., 2009; Holmgren et al., 2010) showed recently that the ketone body metabolite DL-3-hydroxybutyrate (DL-BHB) (4 mM), lactate (4 mM), or pyruvate (5 mM) shifted GABA actions to hyperpolarizing, suggesting that the depolarizing effects of GABA are attributable to inadequate energy supply when glucose is the sole energy source. We now report that, in rat pups (postnatal days 4-7), plasma D-BHB, lactate, and pyruvate levels are 0.9, 1.5, and 0.12 mM, respectively. Then, we show that DL-BHB (4 mM) and pyruvate (200 μM) do not affect (i) the driving force for GABA(A) receptor-mediated currents (DF(GABA)) in cell-attached single-channel recordings, (2) the resting membrane potential and reversal potential of synaptic GABA(A) receptor-mediated responses in perforated patch recordings, (3) the action potentials triggered by focal GABA applications, or (4) the GDPs determined with electrophysiological recordings and dynamic two-photon calcium imaging. Only very high nonphysiological concentrations of pyruvate (5 mM) reduced DF(GABA) and blocked GDPs. Therefore, DL-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect. There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain.

Electrically evoked compound action potentials recorded from the sheep spinal cord.

PubMed

Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Laird, James; Gorman, Robert B; Ladd, Leigh A; Cousins, Michael J

2013-01-01

The study aims to characterize the electrical response of dorsal column axons to depolarizing stimuli to help understand the mechanisms of spinal cord stimulation (SCS) for the relief of chronic pain. We recorded electrically evoked compound action potentials (ECAPs) during SCS in 10 anesthetized sheep using stimulating and recording electrodes on the same epidural SCS leads. A novel stimulating and recording system allowed artifact contamination of the ECAP to be minimized. The ECAP in the sheep spinal cord demonstrates a triphasic morphology, with P1, N1, and P2 peaks. The amplitude of the ECAP varies along the length of the spinal cord, with minimum amplitudes recorded from electrodes positioned over each intervertebral disc, and maximum amplitudes recorded in the midvertebral positions. This anatomically correlated depression of ECAP also correlates with the areas of the spinal cord with the highest thresholds for stimulation; thus regions of weakest response invariably had least sensitivity to stimulation by as much as a factor of two. The choice of stimulating electrode location can therefore have a profound effect on the power consumption for an implanted stimulator for SCS. There may be optimal positions for stimulation in the sheep, and this observation may translate to humans. Almost no change in conduction velocity (∼100 ms) was observed with increasing currents from threshold to twice threshold, despite increased Aβ fiber recruitment. Amplitude of sheep Aβ fiber potentials during SCS exhibit dependence on electrode location, highlighting potential optimization of Aβ recruitment and power consumption in SCS devices. © 2013 International Neuromodulation Society.

Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

PubMed

Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

2015-05-01

Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

PubMed

Yang, Li-Zhen; Zhu, Yi-Chun

2015-07-05

We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues.

PubMed

Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M

2013-08-01

Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D for the first time using macroporous nanoelectronic scaffolds that are analogous to synthetic tissue scaffold and the extracellular matrix in tissue. Free-standing 3D nanoelectronic scaffolds were cultured with neurons, cardiomyocytes and smooth muscle cells to yield electronically-innervated synthetic or 'cyborg' tissues. Measurements demonstrate that innervated tissues exhibit similar cell viability as with conventional tissue scaffolds, and importantly, demonstrate that the real-time response to drugs and pH changes can be mapped in 3D through the tissues. These results open up a new field of research, wherein nanoelectronics are merged with biological systems in 3D thereby providing broad opportunities, ranging from a nanoelectronic/tissue platform for real-time pharmacological screening in 3D to implantable 'cyborg' tissues enabling closed-loop monitoring and treatment of diseases. Furthermore, the capability of high density scale-up of the above extra- and intracellular nanoscopic probes for action potential recording provide important tools for large-scale high spatio-temporal resolution electrical neural activity mapping in both 2D and 3D, which promises to have a profound impact on many research areas, including the mapping of activity within the brain.

Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues

PubMed Central

Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M.

2013-01-01

Summary Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signals with high signal-to-noise ratio and temporal resolution from cultured neurons, cultured cardiomyocytes, acute brain slices and whole animal hearts. Measurements made with modulation-doped nanoscale active channel SiNW FETs demonstrate that signals recorded from cardiomyocytes are highly localized and have improved time resolution compared to larger planar detectors. In addition, several novel three-dimensional (3D) transistor probes, which were realized using advanced nanowire synthesis methods, have been implemented for intracellular recording. These novel probes include (i) flexible 3D kinked nanowire FETs, (ii) branched intracellular nanotube SiNW FETs, and (iii) active silicon nanotube FETs. Following phospholipid modification of the probes to mimic the cell membrane, the kinked nanowire, branched intracellular nanotube and active silicon nanotube FET probes recorded full-amplitude intracellular action potentials from spontaneously firing cardiomyocytes. Moreover, these probes demonstrated the capability of reversible, stable, and long-term intracellular recording, thus indicating the minimal invasiveness of the new nanoscale structures and suggesting biomimetic internalization via the phospholipid modification. Simultaneous, multi-site intracellular recording from both single cells and cell networks were also readily achieved by interfacing independently addressable nanoprobe devices with cells. Finally, electronic and biological systems have been seamlessly merged in 3D for the first time using macroporous nanoelectronic scaffolds that are analogous to synthetic tissue scaffold and the extracellular matrix in tissue. Free-standing 3D nanoelectronic scaffolds were cultured with neurons, cardiomyocytes and smooth muscle cells to yield electronically-innervated synthetic or ‘cyborg’ tissues. Measurements demonstrate that innervated tissues exhibit similar cell viability as with conventional tissue scaffolds, and importantly, demonstrate that the real-time response to drugs and pH changes can be mapped in 3D through the tissues. These results open up a new field of research, wherein nanoelectronics are merged with biological systems in 3D thereby providing broad opportunities, ranging from a nanoelectronic/tissue platform for real-time pharmacological screening in 3D to implantable ‘cyborg’ tissues enabling closed-loop monitoring and treatment of diseases. Furthermore, the capability of high density scale-up of the above extra- and intracellular nanoscopic probes for action potential recording provide important tools for large-scale high spatio-temporal resolution electrical neural activity mapping in both 2D and 3D, which promises to have a profound impact on many research areas, including the mapping of activity within the brain. PMID:24073014

Decreased afferent excitability contributes to synaptic depression during high-frequency stimulation in hippocampal area CA1

PubMed Central

Kim, Eunyoung; Owen, Benjamin; Holmes, William R.

2012-01-01

Long-term potentiation (LTP) is often induced experimentally by continuous high-frequency afferent stimulation (HFS), typically at 100 Hz for 1 s. Induction of LTP requires postsynaptic depolarization and voltage-dependent calcium influx. Induction is more effective if the same number of stimuli are given as a series of short bursts rather than as continuous HFS, in part because excitatory postsynaptic potentials (EPSPs) become strongly depressed during HFS, reducing postsynaptic depolarization. In this study, we examined mechanisms of EPSP depression during HFS in area CA1 of rat hippocampal brain slices. We tested for presynaptic terminal vesicle depletion by examining minimal stimulation-evoked excitatory postsynaptic currents (EPSCs) during 100-Hz HFS. While transmission failures increased, consistent with vesicle depletion, EPSC latencies also increased during HFS, suggesting a decrease in afferent excitability. Extracellular recordings of Schaffer collateral fiber volleys confirmed a decrease in afferent excitability, with decreased fiber volley amplitudes and increased latencies during HFS. To determine the mechanism responsible for fiber volley changes, we recorded antidromic action potentials in single CA3 pyramidal neurons evoked by stimulating Schaffer collateral axons. During HFS, individual action potentials decreased in amplitude and increased in latency, and these changes were accompanied by a large increase in the probability of action potential failure. Time derivative and phase-plane analyses indicated decreases in both axon initial segment and somato-dendritic components of CA3 neuron action potentials. Our results indicate that decreased presynaptic axon excitability contributes to depression of excitatory synaptic transmission during HFS at synapses between Schaffer collaterals and CA1 pyramidal neurons. PMID:22773781

Double peak sensory nerve action potentials to single stimuli in nerve conduction studies.

PubMed

Leote, Joao; Pereira, Pedro; Valls-Sole, Josep

2017-05-01

In humans, sensory nerve action potentials (SNAPs) can show 2 separate deflections, i.e., double peak potentials (DPp), which necessarily means that 1 peak is delayed with respect to the other. DPps may have various origins and be due to either physical or physiological properties. We review the nature of commonly encountered DPps in clinical practice, provide the most likely interpretations for their physiological origin, and assess their reproducibility and clinical utility. We classified the DPps into 3 categories: (1) simultaneous anodal and cathodal stimulation. (2) simultaneous recording from 2 different nerves at the same site, and (3) SNAP desynchronization. Although the recording of DPps is not a standardized neurophysiological method, their study brings interesting cues about the physiology of nerve stimulation and paves the way for clinical application of such an observation. Muscle Nerve 55: 619-625, 2017. © 2016 Wiley Periodicals, Inc.

Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues.

PubMed

Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M

2016-09-01

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

Three-dimensional mapping and regulation of action potential propagation in nanoelectronics innervated tissues

PubMed Central

Dai, Xiaochuan; Zhou, Wei; Gao, Teng; Liu, Jia; Lieber, Charles M.

2016-01-01

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could impact broadly fundamental scientific and clinical studies, yet realization lacks effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and sub-millisecond time-resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues, and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multi-site stimulation and mapping to manipulate actively the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics. PMID:27347837

Sodium and potassium conductance changes during a membrane action potential.

PubMed

Bezanilla, F; Rojas, E; Taylor, R E

1970-12-01

1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential.

Subliminal display of action words interferes with motor planning: a combined EEG and kinematic study.

PubMed

Boulenger, Véronique; Silber, Beata Y; Roy, Alice C; Paulignan, Yves; Jeannerod, Marc; Nazir, Tatjana A

2008-01-01

Recent evidence has shown that processing action-related language and motor action share common neural representations to a point that the two processes can interfere when performed concurrently. To support the assumption that language-induced motor activity contributes to action word understanding, the present study aimed at ruling out that this activity results from mental imagery of the movements depicted by the words. For this purpose, we examined cross-talk between action word processing and an arm reaching movement, using words that were presented too fast to be consciously perceived (subliminally). Encephalogram (EEG) and movement kinematics were recorded. EEG recordings of the "Readiness potential" ("RP", indicator of motor preparation) revealed that subliminal displays of action verbs during movement preparation reduced the RP and affected the subsequent reaching movement. The finding that motor processes were modulated by language processes despite the fact that words were not consciously perceived, suggests that cortical structures that serve the preparation and execution of motor actions are indeed part of the (action) language processing network.

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dexterous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

DTIC Science & Technology

2016-10-01

isolated action potentials or multi-action potential activity from residual peripheral nerve while patient intends movements of amputated hand/arm...Subtask 3.1: Mapping of neural activity (Months 4 – 36) • Patients will be asked to intend a number of individual finger and multiple finger flexion...during these intended movements. We will map the different intended movements onto the neural activity recorded on the electrodes of the micro-electrode

Ionotropic glutamate receptor GluA4 and T-type calcium channel Cav 3.1 subunits control key aspects of synaptic transmission at the mouse L5B-POm giant synapse.

PubMed

Seol, Min; Kuner, Thomas

2015-12-01

The properties and molecular determinants of synaptic transmission at giant synapses connecting layer 5B (L5B) neurons of the somatosensory cortex (S1) with relay neurons of the posteriomedial nucleus (POm) of the thalamus have not been investigated in mice. We addressed this by using direct electrical stimulation of fluorescently labelled single corticothalamic terminals combined with molecular perturbations and whole-cell recordings from POm relay neurons. Consistent with their function as drivers, we found large-amplitude excitatory postsynaptic currents (EPSCs) and multiple postsynaptic action potentials triggered by a single presynaptic action potential. To study the molecular basis of these two features, ionotropic glutamate receptors and low voltage-gated T-type calcium channels were probed by virus-mediated genetic perturbation. Loss of GluA4 almost abolished the EPSC amplitude, strongly delaying the onset of action potential generation, but maintaining the number of action potentials generated per presynaptic action potential. In contrast, knockdown of the Cav 3.1 subunit abrogated the driver function of the synapse at a typical resting membrane potential of -70 mV. However, when depolarizing the membrane potential to -60 mV, the synapse relayed single action potentials. Hence, GluA4 subunits are required to produce an EPSC sufficiently large to trigger postsynaptic action potentials within a defined time window after the presynaptic action potential, while Cav 3.1 expression is essential to establish the driver function of L5B-POm synapses at hyperpolarized membrane potentials. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Development of Action Monitoring through Adolescence into Adulthood: ERP and Source Localization

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Dahl, Ronald E.; Carter, Cameron S.

2007-01-01

In this study we examined the development of three action monitoring event-related potentials (ERPs)--the error-related negativity (ERN/Ne), error positivity (P[subscript E]) and the N2--and estimated their neural sources. These ERPs were recorded during a flanker task in the following groups: early adolescents (mean age = 12 years), late…

Neural correlates of action perception at the onset of functional grasping

PubMed Central

Daum, Moritz M.; Handl, Andrea; Gredebäck, Gustaf

2015-01-01

Event-related potentials were recorded while infants observe congruent or incongruent grasping actions at the age when organized grasping first emerges (4–6 months of age). We demonstrate that the event-related potential component P400 encodes the congruency of power grasps at the age of 6 months (Experiment 1) and in 5-month-old infants that have developed the ability to use power grasps (Experiment 2). This effect does not extend to precision grasps, which infants cannot perform (Experiment 3). Our findings suggest that infants’ encoding of the relationship between an object and a grasping hand (the action–perception link) is highly specialized to actions and manual configurations of actions that infants are able to perform. PMID:25193947

Na and Ca components of action potentials in amphioxus muscle cells

PubMed Central

Hagiwara, S.; Kidokoro, Y.

1971-01-01

1. The ionic mechanism of the action potential produced in lamella-like muscle cells of amphioxus, Branchiostoma californiense, was investigated with intracellular recording and polarization techniques. 2. The resting potential and action potential overshoot in normal saline are -53±5 mV (S.D.) and +29±10 mV (S.D.) respectively. 3. The action potential is eliminated by tetrodotoxin (3 μM) and by replacing NaCl in the saline with Tris-chloride but maintained by replacing Na with Li. 4. After elimination of the normal action potential by tetrodotoxin or replacing Na with Tris, the addition of procaine (7·3 mM) to the external saline makes the membrane capable of producing a regenerative potential change. 5. The peak potential of the regenerative response depends on external Ca concentration in a manner predicted by the Nernst equation with Ca concentrations close to normal. 6. The Ca dependent response is reversibly suppressed by Co or La ions. 7. Similar regenerative responses are obtained when Ca is substituted with Sr or Ba. 8. It is concluded that two independent mechanisms of ionic permeability increase occur in the membrane of amphioxus muscle cell, one to Na and the other to Ca. PMID:5158595

Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

PubMed

Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

2014-01-01

Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Short infrared laser pulses block action potentials in neurons

NASA Astrophysics Data System (ADS)

Walsh, Alex J.; Tolstykh, Gleb P.; Martens, Stacey L.; Ibey, Bennett L.; Beier, Hope T.

2017-02-01

Short infrared laser pulses have many physiological effects on cells including the ability to stimulate action potentials in neurons. Here we show that short infrared laser pulses can also reversibly block action potentials. Primary rat hippocampal neurons were transfected with the Optopatch2 plasmid, which contains both a blue-light activated channel rhodopsin (CheRiff) and a red-light fluorescent membrane voltage reporter (QuasAr2). This optogenetic platform allows robust stimulation and recording of action potential activity in neurons in a non-contact, low noise manner. For all experiments, QuasAr2 was imaged continuously on a wide-field fluorescent microscope using a Krypton laser (647 nm) as the excitation source and an EMCCD camera operating at 1000 Hz to collect emitted fluorescence. A co-aligned Argon laser (488 nm, 5 ms at 10Hz) provided activation light for CheRiff. A 200 mm fiber delivered infrared light locally to the target neuron. Reversible action potential block in neurons was observed following a short infrared laser pulse (0.26-0.96 J/cm2; 1.37-5.01 ms; 1869 nm), with the block persisting for more than 1 s with exposures greater than 0.69 J/cm2. Action potential block was sustained for 30 s with the short infrared laser pulsed at 1-7 Hz. Full recovery of neuronal activity was observed 5-30s post-infrared exposure. These results indicate that optogenetics provides a robust platform for the study of action potential block and that short infrared laser pulses can be used for non-contact, reversible action potential block.

Examination of a demyelinated fiber by action-potential-encoded second harmonic generation

NASA Astrophysics Data System (ADS)

Chen, Xin-guang; Luo, Zhi-hui; Yang, Hong-qin; Huang, Yi-mei; Xie, Shu-sen

2012-03-01

Axonal demyelination is a common phenomenon in the nervous system in human. Conventional measured approaches such as surface recording electrode and diffusion tensor imaging, are hard to fast and accurately determine the demyelinated status of a fiber. In this study, we first presented a mathematical model of nerve fiber demyelination, and it was combined with second harmonic generation(SHG) technique to study the characteristics of action-potential-encoded SHG and analyze the sensitivity of SHG signals responded to membrane potential. And then, we used this approach to fast examine the injured myelin sheaths resulted from demyelination. Each myelin sheath of a fiber was examined simultaneously by this approach. The results showed that fiber demyelination led to observable attenuation of action potential amplitude. The delay of action potential conduction would be markedly observed when the fiber demyelination was more than 80%. Furthermore, the normal and injured myelin sheaths of a myelinated fiber could be distinguished via the changes of SHG signals, which revealed the possibility of SHG technique in the examination of a demyelinated fiber. Our study shows that this approach may have potential application values in clinic.

[Effect of pulse magnetic field on distribution of neuronal action potential].

PubMed

Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

2014-08-25

The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

ELECTRIC IMPEDANCE OF NITELLA DURING ACTIVITY

PubMed Central

Cole, Kenneth S.; Curtis, Howard J.

1938-01-01

The changes in the alternating current impedance which occur during activity of cells of the fresh water plant Nitella have been measured with the current flow normal to the cell axis, at eight frequencies from 0.05 to 20 kilocycles per second, and with simultaneous records of the action potential under the impedance electrodes. At each frequency the resting cell was balanced in a Wheatstone bridge with a cathode ray oscillograph, and after electrical stimulation at one end of the cell, the changes in the complex impedance were determined from the bridge unbalance recorded by motion pictures of the oscillograph figure. An extension of the previous technique of interpretation of the transverse impedance shows that the normal membrane capacity of 0.9 µf./cm.2 decreases about 15 per cent without change of phase angle, while the membrane resistance decreases from 105 ohm cm.2 to about 500 ohm cm.2 during the passage of the excitation wave. This membrane change occurs during the latter part of the rising phase of the action potential, and it is shown that the membrane electromotive force remains unchanged until nearly the same time. The part of the action potential preceding these membrane changes is probably a passive fall of potential ahead of a partial short circuit. PMID:19873091

The pacemaker activity generating the intrinsic myogenic contraction of the dorsal vessel of Tenebrio molitor (Coleoptera).

PubMed

Markou, T; Theophilidis, G

2000-11-01

Combined intracellular and extracellular recordings from various parts of the isolated dorsal vessel of Tenebrio molitor revealed some of the following electrophysiological properties of the heart and the aorta. (i) The wave of depolarization causing forward pulsation of the dorsal vessel was always transmitted from posterior to anterior, with a conduction velocity of 0.014 m s(-1) in the heart and 0.001 m s(-1) in the aorta when the heart rate was 60 beats min(-1). (ii) There was no pacemaker activity in the aorta. (iii) The duration of the compound action potential in the aortic muscle depended on the duration of the pacemaker action potential generated in the heart. (iv) Isolated parts of the heart continued to contract rhythmically for hours, indicating powerful pacemaker activity in individual cardiac segments. (v) There was a direct relationship between action potential duration and the length of the preceding diastolic interval. (vi) The rhythmic wave of depolarization was dependent on the influx of Ca(2+). (vii) The recovery of the electrical properties of myocardial cells that had been disrupted by sectioning was rapid. (viii) In hearts sectioned into two halves, the rhythmic pacemaker action potentials recorded simultaneously from the two isolated halves eventually drifted out of phase, but they had the same intrinsic frequency. In the light of these data, we discuss two alternative models for the generation of spontaneous rhythmic pumping movements of the heart and aorta.

Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

PubMed

Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

2017-04-01

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

PubMed Central

Saung, Wint Thu; Foskett, J. Kevin

2017-01-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells.

PubMed

Ma, Zhongming; Saung, Wint Thu; Foskett, J Kevin

2017-05-01

Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na + currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na + and K + channels but contributed modestly to the kinetics of action potentials. Copyright © 2017 the American Physiological Society.

A feasibility study of multi-site,intracellular recordings from mammalian neurons by extracellular gold mushroom-shaped microelectrodes.

PubMed

Ojovan, Silviya M; Rabieh, Noha; Shmoel, Nava; Erez, Hadas; Maydan, Eilon; Cohen, Ariel; Spira, Micha E

2015-09-14

The development of multi-electrode array platforms for large scale recording of neurons is at the forefront of neuro-engineering research efforts. Recently we demonstrated, at the proof-of-concept level, a breakthrough neuron-microelectrode interface in which cultured Aplysia neurons tightly engulf gold mushroom-shaped microelectrodes (gMμEs). While maintaining their extracellular position, the gMμEs record synaptic- and action-potentials with characteristic features of intracellular recordings. Here we examined the feasibility of using gMμEs for intracellular recordings from mammalian neurons. To that end we experimentally examined the innate size limits of cultured rat hippocampal neurons to engulf gMμEs and measured the width of the "extracellular" cleft formed between the neurons and the gold surface. Using the experimental results we next analyzed the expected range of gMμEs-neuron electrical coupling coefficients. We estimated that sufficient electrical coupling levels to record attenuated synaptic- and action-potentials can be reached using the gMμE-neuron configuration. The definition of the engulfment limits of the gMμEs caps diameter at ≤2-2.5 μm and the estimated electrical coupling coefficients from the simulations pave the way for rational development and application of the gMμE based concept for in-cell recordings from mammalian neurons.

Recording and assessment of evoked potentials with electrode arrays.

PubMed

Miljković, N; Malešević, N; Kojić, V; Bijelić, G; Keller, T; Popović, D B

2015-09-01

In order to optimize procedure for the assessment of evoked potentials and to provide visualization of the flow of action potentials along the motor systems, we introduced array electrodes for stimulation and recording and developed software for the analysis of the recordings. The system uses a stimulator connected to an electrode array for the generation of evoked potentials, an electrode array connected to the amplifier, A/D converter and computer for the recording of evoked potentials, and a dedicated software application. The method has been tested for the assessment of the H-reflex on the triceps surae muscle in six healthy humans. The electrode array with 16 pads was positioned over the posterior aspect of the thigh, while the recording electrode array with 16 pads was positioned over the triceps surae muscle. The stimulator activated all the pads of the stimulation electrode array asynchronously, while the signals were recorded continuously at all the recording sites. The results are topography maps (spatial distribution of evoked potentials) and matrices (spatial visualization of nerve excitability). The software allows the automatic selection of the lowest stimulation intensity to achieve maximal H-reflex amplitude and selection of the recording/stimulation pads according to predefined criteria. The analysis of results shows that the method provides rich information compared with the conventional recording of the H-reflex with regard the spatial distribution.

Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact.

PubMed

Kent, A R; Grill, W M

2012-06-01

The clinical efficacy of deep brain stimulation (DBS) for the treatment of movement disorders depends on the identification of appropriate stimulation parameters. Since the mechanisms of action of DBS remain unclear, programming sessions can be time consuming, costly and result in sub-optimal outcomes. Measurement of electrically evoked compound action potentials (ECAPs) during DBS, generated by activated neurons in the vicinity of the stimulating electrode, could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulation parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1000 to 5000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 µs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters.

Label-free optical detection of action potential in mammalian neurons (Conference Presentation)

NASA Astrophysics Data System (ADS)

Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra K.; Davé, Digant P.

2017-02-01

Electrophysiology techniques are the gold standard in neuroscience for studying functionality of a single neuron to a complex neuronal network. However, electrophysiology techniques are not flawless, they are invasive nature, procedures are cumbersome to implement with limited capability of being used as a high-throughput recording system. Also, long term studies of neuronal functionality with aid of electrophysiology is not feasible. Non-invasive stimulation and detection of neuronal electrical activity has been a long standing goal in neuroscience. Introduction of optogenetics has ushered in the era of non-invasive optical stimulation of neurons, which is revolutionizing neuroscience research. Optical detection of neuronal activity that is comparable to electro-physiology is still elusive. A number of optical techniques have been reported recording of neuronal electrical activity but none is capable of reliably measuring action potential spikes that is comparable to electro-physiology. Optical detection of action potential with voltage sensitive fluorescent reporters are potential alternatives to electrophysiology techniques. The heavily rely on secondary reporters, which are often toxic in nature with background fluorescence, with slow response and low SNR making them far from ideal. The detection of one shot (without averaging)-single action potential in a true label-free way has been elusive so far. In this report, we demonstrate the optical detection of single neuronal spike in a cultured mammalian neuronal network without using any exogenous labels. To the best of our knowledge, this is the first demonstration of label free optical detection of single action potentials in a mammalian neuronal network, which was achieved using a high-speed phase sensitive interferometer. We have carried out stimulation and inhibition of neuronal firing using Glutamate and Tetrodotoxin respectively to demonstrate the different outcome (stimulation and inhibition) revealed in optical signal. We hypothesize that the interrogating optical beam is modulated during neuronal firing by electro-motility driven membrane fluctuation in conjunction with electrical wave propagation in cellular system.

Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

PubMed

Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

2017-07-01

Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na + and K + channel function could reliably reproduce the observed increase in action potential firing and altered action potential waveform. These results, in conjunction with our prior findings on L5 neurons, suggest that principal neurons in the circuitry of the medial prefrontal cortex are altered in distinct ways in the fmr1 -/y mouse and may contribute to dysfunctional prefrontal cortex processing in fragile X syndrome. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

PubMed

Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

2012-01-01

Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

The Direct Detection of a Single Evoked Action Potential with Magnetic Resonance Spectroscopy in Lumbricus Terrestris

PubMed Central

Poplawsky, Alexander J.; Dingledine, Raymond

2011-01-01

Functional MRI (fMRI) indirectly measures neural activity by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In the present study, we used magnetic resonance to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free-induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of [-1.2 ± 0.3] ×10-5 radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase due to a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using magnetic resonance. PMID:21728204

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

PubMed

Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Sodium and potassium conductance changes during a membrane action potential

PubMed Central

Bezanilla, Francisco; Rojas, Eduardo; Taylor, Robert E.

1970-01-01

1. A method for turning a membrane potential control system on and off in less than 10 μsec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential. 2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential. 3. The total membrane conductance taken from these current—voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939). 4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin—Huxley equations. 5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

PubMed Central

Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

2010-01-01

Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

Presynaptic and postsynaptic effects of local cathodal DC polarization within the spinal cord in anaesthetized animal preparations

PubMed Central

Bolzoni, F; Jankowska, E

2015-01-01

The present study aimed to compare presynaptic and postsynaptic actions of direct current polarization in the spinal cord, focusing on DC effects on primary afferents and motoneurons. To reduce the directly affected spinal cord region, a weak polarizing direct current (0.1–0.3 μA) was applied locally in deeply anaesthetized cats and rats; within the hindlimb motor nuclei in the caudal lumbar segments, or in the dorsal horn within the terminal projection area of low threshold skin afferents. Changes in the excitability of primary afferents activated by intraspinal stimuli (20–50 μA) were estimated using increases or decreases in compound action potentials recorded from the dorsal roots or peripheral nerves as their measure. Changes in the postsynaptic actions of the afferents were assessed from intracellularly recorded monosynaptic EPSPs in hindlimb motoneurons and monosynaptic extracellular field potentials (evoked by group Ia afferents in motor nuclei, or by low threshold cutaneous afferents in the dorsal horn). The excitability of motoneurons activated by intraspinal stimuli was assessed using intracellular records or motoneuronal discharges recorded from a ventral root or a muscle nerve. Cathodal polarization was found to affect motoneurons and afferents providing input to them to a different extent. The excitability of both was markedly increased during DC application, although post-polarization facilitation was found to involve presynaptic afferents and some of their postsynaptic actions, but only negligibly motoneurons themselves. Taken together, these results indicate that long-lasting post-polarization facilitation of spinal activity induced by locally applied cathodal current primarily reflects the facilitation of synaptic transmission. PMID:25416625

Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

PubMed Central

Guo, Tianruo; Al Abed, Amr; Lovell, Nigel H.; Dokos, Socrates

2013-01-01

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation. PMID:23710254

Electrical signaling and photosynthesis: can they co-exist together?

PubMed

Pavlovič, Andrej; Mancuso, Stefano

2011-06-01

Mechanical irritation of trigger hairs and subsequent generation of action potentials have significant impact on photosynthesis and respiration in carnivorous Venus flytrap (Dionaea muscipula). Action potential-mediated inhibition of photosynthesis and stimulation of respiration is confined only to the trap and was not recorded in adjacent photosynthetic lamina. We showed that the main primary target of electrical signals on assimilation is in the dark enzymatic reaction of photosynthesis. Without doubt, the electrical signaling is costly, and the possible co-existence of such type of signals and photosynthesis in plant cell is discussed.

Optical transmembrane potential measurements during defibrillation-strength shocks in perfused rabbit hearts.

PubMed

Zhou, X; Ideker, R E; Blitchington, T F; Smith, W M; Knisley, S B

1995-09-01

To study the optical transmembrane potential change (delta F) induced during shocks, optical recordings were obtained in 15 isolated perfused rabbit hearts treated with the potentiometric dye di-4-ANEPPS and diacetyl monoxime. Shock electrodes were sutured on the right and left ventricles. A laser beam 30 microns in diameter was used to optically excite di-4-ANEPPS. Fluorescence from a region 150 microns in diameter was recorded during a shock. In the macroscopic study (six animals), there were nine recording spots that were 3 mm apart between the two shock electrodes. In the microscopic study, there were three recording regions that were 3 mm away from either shock electrode and midway between them, with nine recording spots that were 30 microns (three animals), 100 microns (three animals), and 300 microns (three animals) apart in each region. After 20 S1 stimuli, a 10-ms truncated exponential S2 shock of defibrillation-threshold strength was given during the plateau of the last S1 action potential. In the microscopic study, shocks were also given during diastole, with delta F recordings at the three recording regions. Shocks of both polarities were tested. delta F during the shock was expressed as a percentage of the fluorescence change during the S1 upstroke action potential amplitude (the S1 Fapa), ie, delta F/Fapa%. In the macroscopic study, the magnitudes of delta F/Fapa% from recording spots 1 to 9, numbered from the left to the right ventricular electrodes, were 77 +/- 41%, 46 +/- 32%, 32 +/- 27%, 28 +/- 20%, 37 +/- 25%, 24 +/- 20%, 33 +/- 22%, 37 +/- 25%, and 59 +/- 29%, respectively (P < .05 among the nine spots). Depolarization or hyperpolarization could occur near either shock electrode with both shock polarities, but the magnitude of hyperpolarization was 1.8 +/- 0.9 times that of depolarization at the same recording spot when the shock polarity was reversed (P < .01). In the microscopic study, the change in delta F/Fapa% varied significantly over the microscopic regions examined. The maximum values of delta F/Fapa% for hyperpolarizing shocks during diastole reached only 7 +/- 10% of those for shocks during the plateau (P < .01). During diastole, the time until a new action potential occurred after the beginning of the shock was shorter when the membrane was depolarized (1.1 +/- 0.5 ms) than when it was hyperpolarized (12.8 +/- 9.1 ms, P < .01). Conclusions are as follows: (1) A shock can induce either hyperpolarization or depolarization. (2) Hyperpolarization or depolarization during a shock can occur near either the anodal or cathodal shock electrode. (3) Variation of delta F/Fapa% exists within a microscopic region.(ABSTRACT TRUNCATED AT 400 WORDS)

Naturalistic stimulation changes the dynamic response of action potential encoding in a mechanoreceptor

PubMed Central

Pfeiffer, Keram; French, Andrew S.

2015-01-01

Naturalistic signals were created from vibrations made by locusts walking on a Sansevieria plant. Both naturalistic and Gaussian noise signals were used to mechanically stimulate VS-3 slit-sense mechanoreceptor neurons of the spider, Cupiennius salei, with stimulus amplitudes adjusted to give similar firing rates for either stimulus. Intracellular microelectrodes recorded action potentials, receptor potential, and receptor current, using current clamp and voltage clamp. Frequency response analysis showed that naturalistic stimulation contained relatively more power at low frequencies, and caused increased neuronal sensitivity to higher frequencies. In contrast, varying the amplitude of Gaussian stimulation did not change neuronal dynamics. Naturalistic stimulation contained less entropy than Gaussian, but signal entropy was higher than stimulus in the resultant receptor current, indicating addition of uncorrelated noise during transduction. The presence of added noise was supported by measuring linear information capacity in the receptor current. Total entropy and information capacity in action potentials produced by either stimulus were much lower than in earlier stages, and limited to the maximum entropy of binary signals. We conclude that the dynamics of action potential encoding in VS-3 neurons are sensitive to the form of stimulation, but entropy and information capacity of action potentials are limited by firing rate. PMID:26578975

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

PubMed

Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

2016-01-01

Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance

PubMed Central

Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

2016-01-01

Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents. PMID:27525414

Effect of ischaemia on somatosensory evoked potentials in diabetic patients.

PubMed Central

López-Alburquerque, T; García Miguel, A; Ruiz Ezquerro, J J; de Portugal Alvarez, J

1987-01-01

The nerve action potential at the elbow and somatosensory evoked potentials (SEPs) at the scalp were recorded over 30 minutes of tourniquet-induced limb ischaemia in 10 diabetic patients and 10 controls. According to the SEP changes, an increased resistance to nerve ischaemia in diabetic patients was observed. The pathways involved in SEP conduction are discussed. PMID:3585354

A double-sided microscope to realize whole-ganglion imaging of membrane potential in the medicinal leech

PubMed Central

Wagenaar, Daniel A

2017-01-01

Studies of neuronal network emergence during sensory processing and motor control are greatly facilitated by technologies that allow us to simultaneously record the membrane potential dynamics of a large population of neurons in single cell resolution. To achieve whole-brain recording with the ability to detect both small synaptic potentials and action potentials, we developed a voltage-sensitive dye (VSD) imaging technique based on a double-sided microscope that can image two sides of a nervous system simultaneously. We applied this system to the segmental ganglia of the medicinal leech. Double-sided VSD imaging enabled simultaneous recording of membrane potential events from almost all of the identifiable neurons. Using data obtained from double-sided VSD imaging, we analyzed neuronal dynamics in both sensory processing and generation of behavior and constructed functional maps for identification of neurons contributing to these processes. PMID:28944754

Current-Induced Transistor Sensorics with Electrogenic Cells

PubMed Central

Fromherz, Peter

2016-01-01

The concepts of transistor recording of electroactive cells are considered, when the response is determined by a current-induced voltage in the electrolyte due to cellular activity. The relationship to traditional transistor recording, with an interface-induced response due to interactions with the open gate oxide, is addressed. For the geometry of a cell-substrate junction, the theory of a planar core-coat conductor is described with a one-compartment approximation. The fast electrical relaxation of the junction and the slow change of ion concentrations are pointed out. On that basis, various recording situations are considered and documented by experiments. For voltage-gated ion channels under voltage clamp, the effects of a changing extracellular ion concentration and the enhancement/depletion of ion conductances in the adherent membrane are addressed. Inhomogeneous ion conductances are crucial for transistor recording of neuronal action potentials. For a propagating action potential, the effects of an axon-substrate junction and the surrounding volume conductor are distinguished. Finally, a receptor-transistor-sensor is described, where the inhomogeneity of a ligand–activated ion conductance is achieved by diffusion of the agonist and inactivation of the conductance. Problems with regard to a development of reliable biosensors are mentioned. PMID:27120627

Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery.

PubMed

Shigematsu, Hideki; Kawaguchi, Masahiko; Hayashi, Hironobu; Takatani, Tsunenori; Iwata, Eiichiro; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Tanaka, Yuu; Tanaka, Yasuhito

2017-10-01

During spine surgery, the spinal cord is electrophysiologically monitored via transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) to prevent injury. Transcranial electrical stimulation of motor-evoked potential involves the use of either constant-current or constant-voltage stimulation; however, there are few comparative data available regarding their ability to adequately elicit compound motor action potentials. We hypothesized that the success rates of TES-MEP recordings would be similar between constant-current and constant-voltage stimulations in patients undergoing spine surgery. The objective of this study was to compare the success rates of TES-MEP recordings between constant-current and constant-voltage stimulation. This is a prospective, within-subject study. Data from 100 patients undergoing spinal surgery at the cervical, thoracic, or lumbar level were analyzed. The success rates of the TES-MEP recordings from each muscle were examined. Transcranial electrical stimulation with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions (international "10-20" system) was applied to each patient. Compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles. The success rates of the TES-MEP recordings from the right Del, right APB, bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using constant-voltage stimulation than those using constant-current stimulation. The overall success rates with constant-voltage and constant-current stimulations were 86.3% and 68.8%, respectively (risk ratio 1.25 [95% confidence interval: 1.20-1.31]). The success rates of TES-MEP recordings were higher using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.

PubMed

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-12-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of approximately 5 m s(-1) and approximately 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus

PubMed Central

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-01-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s−1 and ∼0.7 m s−1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+] ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials. PMID:18832425

Motor resonance facilitates movement execution: an ERP and kinematic study

PubMed Central

Ménoret, Mathilde; Curie, Aurore; des Portes, Vincent; Nazir, Tatjana A.; Paulignan, Yves

2013-01-01

Action observation, simulation and execution share neural mechanisms that allow for a common motor representation. It is known that when these overlapping mechanisms are simultaneously activated by action observation and execution, motor performance is influenced by observation and vice versa. To understand the neural dynamics underlying this influence and to measure how variations in brain activity impact the precise kinematics of motor behavior, we coupled kinematics and electrophysiological recordings of participants while they performed and observed congruent or non-congruent actions or during action execution alone. We found that movement velocities and the trajectory deviations of the executed actions increased during the observation of congruent actions compared to the observation of non-congruent actions or action execution alone. This facilitation was also discernible in the motor-related potentials of the participants; the motor-related potentials were transiently more negative in the congruent condition around the onset of the executed movement, which occurred 300 ms after the onset of the observed movement. This facilitation seemed to depend not only on spatial congruency but also on the optimal temporal relationship of the observation and execution events. PMID:24133437

An Emotion-Enriched Context Influences the Effect of Action Observation on Cortical Excitability.

PubMed

Lagravinese, Giovanna; Bisio, Ambra; De Ferrari, Alessia Raffo; Pelosin, Elisa; Ruggeri, Piero; Bove, Marco; Avanzino, Laura

2017-01-01

Observing other people in action activates the "mirror neuron system" that serves for action comprehension and prediction. Recent evidence suggests that this function requires a high level codification triggered not only by components of motor behavior, but also by the environment where the action is embedded. An overlooked component of action perceiving is the one related to the emotional information provided by the context where the observed action takes place. Indeed, whether valence and arousal associated to an emotion might exert an influence on motor system activation during action observation has not been assessed so far. Here, cortico-spinal excitability of the left motor cortex was recorded in three groups of subjects. In the first condition, motor-evoked potential (MEPs) were recorded from a muscle involved in the grasping movement (i.e., abductor pollicis brevis, APB) while participants were watching the same reach-to-grasp movement embedded in contexts with negative emotional valence, but different levels of arousal: sadness (low arousal), and disgust (high arousal) ("Context plus Movement-APB" condition). In the second condition, MEPs were recorded from APB muscle while participants were observing static images representing the contexts in which the movement observed by participants in "Context plus Movement-APB" condition took place ("Context Only-APB" condition). Finally, in the third condition, MEPS were recorded from a muscle not involved in the grasping action, i.e., abductor digiti minimi, ADM, while participants were watching the same videos shown during the "Context plus Movement-APB" condition ("Context plus Movement-ADM" condition). Results showed a greater increase of cortical excitability only during the observation of the hand moving in the context eliciting disgust, and these changes were specific for the muscle involved in the observed action. Our findings show that the emotional context in which a movement occurs modulates motor resonance and that the combination of negative valence/high arousal drives the greater response in the observer's mirror neuron system in a strictly muscle specific fashion.

Electrophysiologic and functional evaluations of regenerated facial nerve defects with a tube containing dental pulp cells in rats.

PubMed

Sasaki, Ryo; Matsumine, Hajime; Watanabe, Yorikatsu; Takeuchi, Yuichi; Yamato, Masayuki; Okano, Teruo; Miyata, Mariko; Ando, Tomohiro

2014-11-01

Dental pulp tissue contains Schwann and neural progenitor cells. Tissue-engineered nerve conduits with dental pulp cells promote facial nerve regeneration in rats. However, no nerve functional or electrophysiologic evaluations were performed. This study investigated the compound muscle action potential recordings and facial functional analysis of dental pulp cell regenerated nerve in rats. A silicone tube containing rat dental pulp cells in type I collagen gel was transplanted into a 7-mm gap of the buccal branch of the facial nerve in Lewis rats; the same defect was created in the marginal mandibular branch, which was ligatured. Compound muscle action potential recordings of vibrissal muscles and facial functional analysis with facial palsy score of the nerve were performed. Tubulation with dental pulp cells showed significantly lower facial palsy scores than the autograft group between 3 and 10 weeks postoperatively. However, the dental pulp cell facial palsy scores showed no significant difference from those of autograft after 11 weeks. Amplitude and duration of compound muscle action potentials in the dental pulp cell group showed no significant difference from those of the intact and autograft groups, and there was no significant difference in the latency of compound muscle action potentials between the groups at 13 weeks postoperatively. However, the latency in the dental pulp cell group was prolonged more than that of the intact group. Tubulation with dental pulp cells could recover facial nerve defects functionally and electrophysiologically, and the recovery became comparable to that of nerve autografting in rats.

Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

PubMed

Chen, Y; Sun, X D; Herness, S

1996-02-01

1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the use of calcium-free bathing solution. It was most obvious at more depolarized holding potentials that inactivated much of the transient and sustained outward currents. 5. Potassium currents contribute to both the repolarization and afterhyperpolarization phases of the action potential. These currents were blocked by bath application of tetraethylammonium, which also substantially broadened the action potential. Application of 4-aminopyridine was able to selectively block transient potassium currents without affecting sustained currents. This also broadened the action potential as well as eliminated the afterhyperpolarization. 6. A second type of action potential was observed that differed in duration. These slow action potentials had t1/2 durations of 9.6 ms compared with 1.4 ms for fast action potentials. Input resistances of the two groups were indistinguishable. Approximately one-fourth of the cells eliciting action potentials were of the slow type. 7. Cells eliciting fast action potentials had large outward currents capable of producing a quick repolarization, whereas cells with slow action potentials had small outward currents by comparison. The average values of fast cells were 2,563 pA and 1.4 ms compared with 373 pA and 9.6 ms for slow cells. Current and duration values were related exponentially. No significant difference was noted for inward currents. 8. These results suggest that many taste receptor cells conduct action potentials, which may be classified broadly into two groups on the basis of action potential duration and potassium current magnitude. These groups may be related to cell turnover. The physiological role of action potentials remains to be elucidated but may be important for communication within the taste bud as well as to the afferent nerve.

Extracellular NAD+ Suppresses Adrenergic Effects in the Atrial Myocardium of Rats during the Early Postnatal Ontogeny.

PubMed

Pustovit, K B; Ivanova, A D; Kuz'min, V S

2018-05-01

The effects of sympathetic cotransmitter NAD+ (10 μM) on bioelectric activity of the heart under conditions of adrenergic stimulation were studied on isolated spontaneously contracting preparations (without stimulation) of the right atrium from 2-7-day-old rats. Action potentials were recorded in the working myocardium using standard microelectrode technique. Perfusion of the right atrium with norepinephrine solution (1 μM) altered the configuration and significantly lengthened the action potentials. NAD + against the background of norepinephrine stimulation significantly decreased the duration of action potentials, in particular, at 25% repolarization. The effect of purine compounds NAD + , ATP, and adenosine on bioelectrical activity of the heart of newborn rats was studied under basal conditions (without norepinephrine stimulation). The effect of NAD + against the background of adrenergic stimulation was more pronounced than under basal conditions and was probably determined by suppression of I CaL , which can be the main mechanism of NAD + action on rat heart.

A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals.

PubMed

Srinivasan, Akhil; Tipton, John; Tahilramani, Mayank; Kharbouch, Adel; Gaupp, Eric; Song, Chao; Venkataraman, Poornima; Falcone, Jessica; Lacour, Stéphanie P; Stanley, Garrett B; English, Arthur W; Bellamkonda, Ravi V

2016-02-01

Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

PubMed

Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

2017-01-01

The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers

PubMed Central

2011-01-01

This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug. The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm. In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized. PMID:21569639

Axonal propagation of simple and complex spikes in cerebellar Purkinje neurons.

PubMed

Khaliq, Zayd M; Raman, Indira M

2005-01-12

In cerebellar Purkinje neurons, the reliability of propagation of high-frequency simple spikes and spikelets of complex spikes is likely to regulate inhibition of Purkinje target neurons. To test the extent to which a one-to-one correspondence exists between somatic and axonal spikes, we made dual somatic and axonal recordings from Purkinje neurons in mouse cerebellar slices. Somatic action potentials were recorded with a whole-cell pipette, and the corresponding axonal signals were recorded extracellularly with a loose-patch pipette. Propagation of spontaneous and evoked simple spikes was highly reliable. At somatic firing rates of approximately 200 spikes/sec, <10% of spikes failed to propagate, with failures becoming more frequent only at maximal somatic firing rates (approximately 260 spikes/sec). Complex spikes were elicited by climbing fiber stimulation, and their somatic waveforms were modulated by tonic current injection, as well as by paired stimulation to depress the underlying EPSCs. Across conditions, the mean number of propagating action potentials remained just above two spikes per climbing fiber stimulation, but the instantaneous frequency of the propagating spikes changed, from approximately 375 Hz during somatic hyperpolarizations that silenced spontaneous firing to approximately 150 Hz during spontaneous activity. The probability of propagation of individual spikelets could be described quantitatively as a saturating function of spikelet amplitude, rate of rise, or preceding interspike interval. The results suggest that ion channels of Purkinje axons are adapted to produce extremely short refractory periods and that brief bursts of forward-propagating action potentials generated by complex spikes may contribute transiently to inhibition of postsynaptic neurons.

In vitro assessment of induced phrenic nerve cryothermal injury.

PubMed

Goff, Ryan P; Bersie, Stephanie M; Iaizzo, Paul A

2014-10-01

Phrenic nerve injury, both left and right, is considered a significant complication of cryoballoon ablation for treatment of drug-refractory atrial fibrillation, and functional recovery of the phrenic nerve can take anywhere from hours to months. The purpose of this study was to focus on short periods of cooling to determine the minimal amount of cooling that may terminate nerve function related to cryo ablation. Left and/or right phrenic nerves were dissected from the pericardium and connective tissue of swine (n = 35 preparations). Nerves were placed in a recording chamber modified with a thermocouple array. This apparatus was placed in a digital water bath to maintain an internal chamber temperature of 37°C. Nerves were stimulated proximally with a 1-V, 0.1-ms square wave. Bipolar compound action potentials were recorded proximal and distal to the site of ablation both before and after ablation, then analyzed to determine changes in latency, amplitude, and duration. Temperatures were recorded at a rate of 5 Hz, and maximum cooling rates were calculated. Phrenic nerves were found to elicit compound action potentials upon stimulation for periods up to 4 hours minimum. Average conduction velocity was 56.7 ± 14.7 m/s preablation and 49.8 ± 16.6 m/s postablation (P = .17). Cooling to mild subzero temperatures ceased production of action potentials for >1 hour. Taking into account the data presented here, previous publications, and a conservative stance, during cryotherapy applications, cooling of the nerve to below 4°C should be avoided whenever possible. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Development of hypersynchrony in the cortical network during chemoconvulsant-induced epileptic seizures in vivo.

PubMed

Cymerblit-Sabba, Adi; Schiller, Yitzhak

2012-03-01

The prevailing view of epileptic seizures is that they are caused by increased hypersynchronous activity in the cortical network. However, this view is based mostly on electroencephalography (EEG) recordings that do not directly monitor neuronal synchronization of action potential firing. In this study, we used multielectrode single-unit recordings from the hippocampus to investigate firing of individual CA1 neurons and directly monitor synchronization of action potential firing between neurons during the different ictal phases of chemoconvulsant-induced epileptic seizures in vivo. During the early phase of seizures manifesting as low-amplitude rhythmic β-electrocorticography (ECoG) activity, the firing frequency of most neurons markedly increased. To our surprise, the average overall neuronal synchronization as measured by the cross-correlation function was reduced compared with control conditions with ~60% of neuronal pairs showing no significant correlated firing. However, correlated firing was not uniform and a minority of neuronal pairs showed a high degree of correlated firing. Moreover, during the early phase of seizures, correlated firing between 9.8 ± 5.1% of all stably recorded pairs increased compared with control conditions. As seizures progressed and high-frequency ECoG polyspikes developed, the firing frequency of neurons further increased and enhanced correlated firing was observed between virtually all neuronal pairs. These findings indicated that epileptic seizures represented a hyperactive state with widespread increase in action potential firing. Hypersynchrony also characterized seizures. However, it initially developed in a small subset of neurons and gradually spread to involve the entire cortical network only in the later more intense ictal phases.

Immunoglobulinfree light chains reduce in an antigen-specific manner the rate of rise of action potentials of mouse non-nociceptive dorsal root ganglion neurons.

PubMed

Rijnierse, Anneke; Kraneveld, Aletta D; Salemi, Arezo; Zwaneveld, Sandra; Goumans, Aleida P H; Rychter, Jakub W; Thio, Marco; Redegeld, Frank A; Westerink, Remco H S; Kroese, Alfons B A

2013-11-15

Plasma B cells secrete immunoglobulinfree light chains (IgLC) which by binding to mast cells can mediate hypersensitivity responses and are involved in several immunological disorders. To investigate the effects of antigen-specific IgLC activation, intracellular recordings were made from cultured murine dorsal root ganglion (DRG) neurons, which can specifically bind IgLC. The neurons were sensitized with IgLC for 90min and subsequently activated by application of the corresponding antigen (DNP-HSA). Antigen application induced a decrease in the rate of rise of the action potentials of non-nociceptive neurons (MANOVA, p=2.10(-6)), without affecting the resting membrane potential or firing threshold. The action potentials of the nociceptive neurons (p=0.57) and the electrical excitability of both types of neurons (p>0.35) were not affected. We conclude that IgLC can mediate antigen-specific responses by reducing the rate of rise of action potentials in non-nociceptive murine DRG neurons. We suggest that antigen-specific activation of IgLC-sensitized non-nociceptive DRG neurons may contribute to immunological hypersensitivity responses and neuroinflammation. © 2013.

An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

PubMed

Fatehi, M; Rowan, E G; Harvey, A L

2002-01-01

The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-12-01

Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and triangulation of epicardial action potential.

Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma.

PubMed

Michalikova, Martina; Remme, Michiel W H; Kempter, Richard

2017-01-01

Spikelets are small spike-like depolarizations that can be measured in somatic intracellular recordings. Their origin in pyramidal neurons remains controversial. To explain spikelet generation, we propose a novel single-cell mechanism: somato-dendritic input generates action potentials at the axon initial segment that may fail to activate the soma and manifest as somatic spikelets. Using mathematical analysis and numerical simulations of compartmental neuron models, we identified four key factors controlling spikelet generation: (1) difference in firing threshold, (2) impedance mismatch, and (3) electrotonic separation between the soma and the axon initial segment, as well as (4) input amplitude. Because spikelets involve forward propagation of action potentials along the axon while they avoid full depolarization of the somato-dendritic compartments, we conjecture that this mode of operation saves energy and regulates dendritic plasticity while still allowing for a read-out of results of neuronal computations.

Conditional Outlier Detection for Clinical Alerting

PubMed Central

Hauskrecht, Milos; Valko, Michal; Batal, Iyad; Clermont, Gilles; Visweswaran, Shyam; Cooper, Gregory F.

2010-01-01

We develop and evaluate a data-driven approach for detecting unusual (anomalous) patient-management actions using past patient cases stored in an electronic health record (EHR) system. Our hypothesis is that patient-management actions that are unusual with respect to past patients may be due to a potential error and that it is worthwhile to raise an alert if such a condition is encountered. We evaluate this hypothesis using data obtained from the electronic health records of 4,486 post-cardiac surgical patients. We base the evaluation on the opinions of a panel of experts. The results support that anomaly-based alerting can have reasonably low false alert rates and that stronger anomalies are correlated with higher alert rates. PMID:21346986

Conditional outlier detection for clinical alerting.

PubMed

Hauskrecht, Milos; Valko, Michal; Batal, Iyad; Clermont, Gilles; Visweswaran, Shyam; Cooper, Gregory F

2010-11-13

We develop and evaluate a data-driven approach for detecting unusual (anomalous) patient-management actions using past patient cases stored in an electronic health record (EHR) system. Our hypothesis is that patient-management actions that are unusual with respect to past patients may be due to a potential error and that it is worthwhile to raise an alert if such a condition is encountered. We evaluate this hypothesis using data obtained from the electronic health records of 4,486 post-cardiac surgical patients. We base the evaluation on the opinions of a panel of experts. The results support that anomaly-based alerting can have reasonably low false alert rates and that stronger anomalies are correlated with higher alert rates.

Large-scale recording of neuronal ensembles.

PubMed

Buzsáki, György

2004-05-01

How does the brain orchestrate perceptions, thoughts and actions from the spiking activity of its neurons? Early single-neuron recording research treated spike pattern variability as noise that needed to be averaged out to reveal the brain's representation of invariant input. Another view is that variability of spikes is centrally coordinated and that this brain-generated ensemble pattern in cortical structures is itself a potential source of cognition. Large-scale recordings from neuronal ensembles now offer the opportunity to test these competing theoretical frameworks. Currently, wire and micro-machined silicon electrode arrays can record from large numbers of neurons and monitor local neural circuits at work. Achieving the full potential of massively parallel neuronal recordings, however, will require further development of the neuron-electrode interface, automated and efficient spike-sorting algorithms for effective isolation and identification of single neurons, and new mathematical insights for the analysis of network properties.

Effects of acetylcholine and noradrenalin on action potentials of isolated rabbit sinoatrial and atrial myocytes.

PubMed

Verkerk, Arie O; Geuzebroek, Guillaume S C; Veldkamp, Marieke W; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1-1000 nM, while a clear-cut frequency dependence in the range of 1-4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins.

Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

PubMed Central

Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

2012-01-01

The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

A role for N-methyl-D-aspartate receptors in norepinephrine-induced long-lasting potentiation in the dentate gyrus.

PubMed

Stanton, P K; Mody, I; Heinemann, U

1989-01-01

Mechanisms of action of norepinephrine (NE) on dentate gyrus granule cells were studied in rat hippocampal slices using extra- and intracellular recordings and measurements of stimulus and amino acid-induced changes in extracellular Ca2+ and K+ concentration. Bath application of NE (10-50 microM) induced long-lasting potentiation of perforant path evoked potentials, and markedly enhanced high-frequency stimulus-induced Ca2+ influx and K+ efflux, actions blocked by beta-receptor antagonists and mimicked by beta agonists. Enhanced Ca2+ influx was primarily postsynaptic, since presynaptic delta [Ca2+]o in the stratum moleculare synaptic field was not altered by NE. Interestingly, the potentiation of both ionic fluxes and evoked population potentials were antagonized by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). Furthermore, NE selectively enhanced the delta [Ca2+]o delta [K+]o and extracellular slow negative field potentials elicited by iontophoretically applied NMDA, but not those induced by the excitatory amino acid quisqualate. These results suggest that granule cell influx of Ca2+ through NMDA ionophores is enhanced by NE via beta-receptor activation. In intracellular recordings, NE depolarized granule cells (4.8 +/- 1.1 mV), and increased input resistance (RN) by 34 +/- 6.5%. These actions were also blocked by either the beta-antagonist propranolol or specific beta 1-blocker metoprolol. Moreover, the depolarization and RN increase persisted for long periods (93 +/- 12 min) after NE washout. In contrast, while NE, in the presence of APV, still depolarized granule cells and increased RN, APV made these actions quickly reversible upon NE washout (16 +/- 9 min). This suggested that NE induction of long-term, but not short-term, plasticity in the dentate gyrus requires NMDA receptor activation. NE may be enhancing granule cell firing by some combination of blockade on the late Ca2+-activated K+ conductance and depolarization of granule cells, both actions that can bring granule cells into a voltage range where NMDA receptors are more easily activated. Furthermore, NE also elicited activity-independent long-lasting depolarization and RN increases, which required functional NMDA receptors to persist.

REVIEW OF SIGNAL DISTORTION THROUGH METAL MICROELECTRODE RECORDING CIRCUITS AND FILTERS

PubMed Central

NELSON, Matthew J.; POUGET, Pierre; NILSEN, Erik A.; PATTEN, Craig D.; SCHALL, Jeffrey D.

2008-01-01

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase-shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data. PMID:18242715

Review of signal distortion through metal microelectrode recording circuits and filters.

PubMed

Nelson, Matthew J; Pouget, Pierre; Nilsen, Erik A; Patten, Craig D; Schall, Jeffrey D

2008-03-30

Interest in local field potentials (LFPs) and action potential shape has increased markedly. The present work describes distortions of these signals that occur for two reasons. First, the microelectrode recording circuit operates as a voltage divider producing frequency-dependent attenuation and phase shifts when electrode impedance is not negligible relative to amplifier input impedance. Because of the much higher electrode impedance at low frequencies, this occurred over frequency ranges of LFPs measured by neurophysiologists for one head-stage tested. Second, frequency-dependent phase shifts are induced by subsequent filters. Thus, we report these effects and the resulting amplitude envelope delays and distortion of waveforms recorded through a commercial data acquisition system and a range of tungsten microelectrodes. These distortions can be corrected, but must be accounted for when interpreting field potential and spike shape data.

Tympanal mechanics and neural responses in the ears of a noctuid moth

NASA Astrophysics Data System (ADS)

Ter Hofstede, Hannah M.; Goerlitz, Holger R.; Montealegre-Z, Fernando; Robert, Daniel; Holderied, Marc W.

2011-12-01

Ears evolved in many groups of moths to detect the echolocation calls of predatory bats. Although the neurophysiology of bat detection has been intensively studied in moths for decades, the relationship between sound-induced movement of the noctuid tympanic membrane and action potentials in the auditory sensory cells (A1 and A2) has received little attention. Using laser Doppler vibrometry, we measured the velocity and displacement of the tympanum in response to pure tone pulses for moths that were intact or prepared for neural recording. When recording from the auditory nerve, the displacement of the tympanum at the neural threshold remained constant across frequencies, whereas velocity varied with frequency. This suggests that the key biophysical parameter for triggering action potentials in the sensory cells of noctuid moths is tympanum displacement, not velocity. The validity of studies on the neurophysiology of moth hearing rests on the assumption that the dissection and recording procedures do not affect the biomechanics of the ear. There were no consistent differences in tympanal velocity or displacement when moths were intact or prepared for neural recordings for sound levels close to neural threshold, indicating that this and other neurophysiological studies provide good estimates of what intact moths hear at threshold.

Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells.

PubMed

Tait, Luke; Wedgwood, Kyle; Tsaneva-Atanasova, Krasimira; Brown, Jon T; Goodfellow, Marc

2018-07-14

The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer's disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4-12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Direct negative chronotropic action of desflurane on sinoatrial node pacemaker activity in the guinea pig heart.

PubMed

Kojima, Akiko; Ito, Yuki; Kitagawa, Hirotoshi; Matsuura, Hiroshi; Nosaka, Shuichi

2014-06-01

Desflurane inhalation is associated with sympathetic activation and concomitant increase in heart rate in humans and experimental animals. There is, however, little information concerning the direct effects of desflurane on electrical activity of sinoatrial node pacemaker cells that determines the intrinsic heart rate. Whole-cell patch-clamp experiments were conducted on guinea pig sinoatrial node pacemaker cells to record spontaneous action potentials and ionic currents contributing to sinoatrial node automaticity, namely, hyperpolarization-activated cation current (If), T-type and L-type Ca currents (ICa,T and ICa,L, respectively), Na/Ca exchange current (INCX), and rapidly and slowly activating delayed rectifier K currents (IKr and IKs, respectively). Electrocardiograms were recorded from ex vivo Langendorff-perfused hearts and in vivo hearts. Desflurane at 6 and 12% decreased spontaneous firing rate of sinoatrial node action potentials by 15.9% (n = 11) and 27.6% (n = 10), respectively, which was associated with 20.4% and 42.5% reductions in diastolic depolarization rate, respectively. Desflurane inhibited If, ICa,T, ICa,L, INCX, and IKs but had little effect on IKr. The negative chronotropic action of desflurane was reasonably well reproduced in sinoatrial node computer model. Desflurane reduced the heart rate in Langendorff-perfused hearts. High concentration (12%) of desflurane inhalation was associated with transient tachycardia, which was totally abolished by pretreatment with the β-adrenergic blocker propranolol. Desflurane has a direct negative chronotropic action on sinoatrial node pacemaking activity, which is mediated by its inhibitory action on multiple ionic currents. This direct inhibitory action of desflurane on sinoatrial node automaticity seems to be counteracted by sympathetic activation associated with desflurane inhalation in vivo.

Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

NASA Technical Reports Server (NTRS)

Cochran, S. L.

1995-01-01

The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the vertebrate neuromuscular junction. The major differences between these two synapses are the neurotransmitters and the higher resting release rate and higher sensitivity of release to increased K+ concentrations of the hair cells over that of motor nerve terminals. These differences reflect the functional roles of the two synapses: the motor nerve terminal response in an all-or-nothing signal consequent from action potential invasion, while the hair cell releases transmitter in a graded fashion, proportionate to the extent of stereocilial deflection. Despite these differences between the two junctions, the similar actions of these elemental cations upon synaptic function at each implies that these ions may participate similarly in the operations of other synapses, independent of the neurotransmitter type.(ABSTRACT TRUNCATED AT 400 WORDS).

The action of chlorphenesin carbamate on the frog spinal cord.

PubMed

Aihara, H; Kurachi, M; Nakane, S; Sasajima, M; Ohzeki, M

1980-02-01

Studies were carried out to elucidate the mechanism of action of chlorphenesin carbamate (CPC) and to compare the effect of the drug with that of mephenesin on the isolated bullfrog spinal cord. Ventral and dorsal root potentials were recorded by means of the sucrose-gap method. CPC caused marked hyperpolarizations and depressed spontaneous activities in both of the primary afferent terminals (PAT) and motoneurons (MN). These hyperpolarizations were observed even in high-Mg2+ and Ca2+-free Ringer's solution, suggesting that CPC has direct actions on PAT and MN. Various reflex potentials (dorsal and ventral root potentials elicited by stimulating dorsal and ventral root, respectively) tended to be depressed by CPC as well as by mephenesin. Excitatory amino acids (L-aspartic acid and L-glutamic acid) caused marked depolarizations in PAT and MN, and increased the firing rate in MN. CPC did not modify the depolarization but abolished the motoneuron firing induced by these amino acids. However, mephenesin reduced both the depolarization and the motoneuron firing. The dorsal and ventral root potentials evoked by tetanic stimulation (40 Hz) of the dorsal root were depressed by the drugs. These results indicate that CPC has an apparent depressing action on the spinal neuron, and this action may be ascribed to the slight hyperpolarization and/or the prolongation of refractory period.

Planar Diamond-Based Multiarrays to Monitor Neurotransmitter Release and Action Potential Firing: New Perspectives in Cellular Neuroscience.

PubMed

Carabelli, Valentina; Marcantoni, Andrea; Picollo, Federico; Battiato, Alfio; Bernardi, Ettore; Pasquarelli, Alberto; Olivero, Paolo; Carbone, Emilio

2017-02-15

High biocompatibility, outstanding electrochemical responsiveness, inertness, and transparency make diamond-based multiarrays (DBMs) first-rate biosensors for in vitro detection of electrochemical and electrical signals from excitable cells together, with potential for in vivo applications as neural interfaces and prostheses. Here, we will review the electrochemical and physical properties of various DBMs and how these devices have been employed for recording released neurotransmitter molecules and all-or-none action potentials from living cells. Specifically, we will overview how DBMs can resolve localized exocytotic events from subcellular compartments using high-density microelectrode arrays (MEAs), or monitoring oxidizable neurotransmitter release from populations of cells in culture and tissue slices using low-density MEAs. Interfacing DBMs with excitable cells is currently leading to the promising opportunity of recording electrical signals as well as creating neuronal interfaces through the same device. Given the recent increasingly growing development of newly available DBMs of various geometries to monitor electrical activity and neurotransmitter release in a variety of excitable and neuronal tissues, the discussion will be limited to planar DBMs.

Organic electronics for high-resolution electrocorticography of the human brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Zhao, Zifang; Yeh, Malcolm; Long, Michael; Greenlee, Jeremy D; Doyle, Werner; Devinsky, Orrin; Buzsáki, György

2016-11-01

Localizing neuronal patterns that generate pathological brain signals may assist with tissue resection and intervention strategies in patients with neurological diseases. Precise localization requires high spatiotemporal recording from populations of neurons while minimizing invasiveness and adverse events. We describe a large-scale, high-density, organic material-based, conformable neural interface device ("NeuroGrid") capable of simultaneously recording local field potentials (LFPs) and action potentials from the cortical surface. We demonstrate the feasibility and safety of intraoperative recording with NeuroGrids in anesthetized and awake subjects. Highly localized and propagating physiological and pathological LFP patterns were recorded, and correlated neural firing provided evidence about their local generation. Application of NeuroGrids to brain disorders, such as epilepsy, may improve diagnostic precision and therapeutic outcomes while reducing complications associated with invasive electrodes conventionally used to acquire high-resolution and spiking data.

Connexin36 vs. connexin32, "miniature" neuronal gap junctions, and limited electrotonic coupling in rodent suprachiasmatic nucleus.

PubMed

Rash, J E; Olson, C O; Pouliot, W A; Davidson, K G V; Yasumura, T; Furman, C S; Royer, S; Kamasawa, N; Nagy, J I; Dudek, F E

2007-10-26

Suprachiasmatic nucleus (SCN) neurons generate circadian rhythms, and these neurons normally exhibit loosely-synchronized action potentials. Although electrotonic coupling has long been proposed to mediate this neuronal synchrony, ultrastructural studies have failed to detect gap junctions between SCN neurons. Nevertheless, it has been proposed that neuronal gap junctions exist in the SCN; that they consist of connexin32 or, alternatively, connexin36; and that connexin36 knockout eliminates neuronal coupling between SCN neurons and disrupts circadian rhythms. We used confocal immunofluorescence microscopy and freeze-fracture replica immunogold labeling to examine the distributions of connexin30, connexin32, connexin36, and connexin43 in rat and mouse SCN and used whole-cell recordings to re-assess electrotonic and tracer coupling. Connexin32-immunofluorescent puncta were essentially absent in SCN but connexin36 was relatively abundant. Fifteen neuronal gap junctions were identified ultrastructurally, all of which contained connexin36 but not connexin32, whereas nearby oligodendrocyte gap junctions contained connexin32. In adult SCN, one neuronal gap junction was >600 connexons, whereas 75% were smaller than 50 connexons, which may be below the limit of detectability by fluorescence microscopy and thin-section electron microscopy. Whole-cell recordings in hypothalamic slices revealed tracer coupling with neurobiotin in <5% of SCN neurons, and paired recordings (>40 pairs) did not reveal obvious electrotonic coupling or synchronized action potentials, consistent with few neurons possessing large gap junctions. However, most neurons had partial spikes or spikelets (often <1 mV), which remained after QX-314 [N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide] had blocked sodium-mediated action potentials within the recorded neuron, consistent with spikelet transmission via small gap junctions. Thus, a few "miniature" gap junctions on most SCN neurons appear to mediate weak electrotonic coupling between limited numbers of neuron pairs, thus accounting for frequent detection of partial spikes and hypothetically providing the basis for "loose" electrical or metabolic synchronization of electrical activity commonly observed in SCN neuronal populations during circadian rhythms.

A PDA-based system for online recording and analysis of concurrent events in complex behavioral processes.

PubMed

Held, Jürgen; Manser, Tanja

2005-02-01

This article outlines how a Palm- or Newton-based PDA (personal digital assistant) system for online event recording was used to record and analyze concurrent events. We describe the features of this PDA-based system, called the FIT-System (flexible interface technique), and its application to the analysis of concurrent events in complex behavioral processes--in this case, anesthesia work processes. The patented FIT-System has a unique user interface design allowing the user to design an interface template with a pencil and paper or using a transparency film. The template usually consists of a drawing or sketch that includes icons or symbols that depict the observer's representation of the situation to be observed. In this study, the FIT-System allowed us to create a design for fast, intuitive online recording of concurrent events using a set of 41 observation codes. An analysis of concurrent events leads to a description of action density, and our results revealed a characteristic distribution of action density during the administration of anesthesia in the operating room. This distribution indicated the central role of the overlapping operations in the action sequences of medical professionals as they deal with the varying requirements of this complex task. We believe that the FIT-System for online recording of concurrent events in complex behavioral processes has the potential to be useful across a broad spectrum of research areas.

The Impact of Experience on Affective Responses during Action Observation.

PubMed

Kirsch, Louise P; Snagg, Arielle; Heerey, Erin; Cross, Emily S

2016-01-01

Perceiving others in action elicits affective and aesthetic responses in observers. The present study investigates the extent to which these responses relate to an observer's general experience with observed movements. Facial electromyographic (EMG) responses were recorded in experienced dancers and non-dancers as they watched short videos of movements performed by professional ballet dancers. Responses were recorded from the corrugator supercilii (CS) and zygomaticus major (ZM) muscles, both of which show engagement during the observation of affect-evoking stimuli. In the first part of the experiment, participants passively watched the videos while EMG data were recorded. In the second part, they explicitly rated how much they liked each movement. Results revealed a relationship between explicit affective judgments of the movements and facial muscle activation only among those participants who were experienced with the movements. Specifically, CS activity was higher for disliked movements and ZM activity was higher for liked movements among dancers but not among non-dancers. The relationship between explicit liking ratings and EMG data in experienced observers suggests that facial muscles subtly echo affective judgments even when viewing actions that are not intentionally emotional in nature, thus underscoring the potential of EMG as a method to examine subtle shifts in implicit affective responses during action observation.

Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes

NASA Astrophysics Data System (ADS)

Jayant, Krishna; Hirtz, Jan J.; Plante, Ilan Jen-La; Tsai, David M.; de Boer, Wieteke D. A. M.; Semonche, Alexa; Peterka, Darcy S.; Owen, Jonathan S.; Sahin, Ozgur; Shepard, Kenneth L.; Yuste, Rafael

2017-05-01

Dendritic spines are the primary site of excitatory synaptic input onto neurons, and are biochemically isolated from the parent dendritic shaft by their thin neck. However, due to the lack of direct electrical recordings from spines, the influence that the neck resistance has on synaptic transmission, and the extent to which spines compartmentalize voltage, specifically excitatory postsynaptic potentials, albeit critical, remains controversial. Here, we use quantum-dot-coated nanopipette electrodes (tip diameters ∼15-30 nm) to establish the first intracellular recordings from targeted spine heads under two-photon visualization. Using simultaneous somato-spine electrical recordings, we find that back propagating action potentials fully invade spines, that excitatory postsynaptic potentials are large in the spine head (mean 26 mV) but are strongly attenuated at the soma (0.5-1 mV) and that the estimated neck resistance (mean 420 MΩ) is large enough to generate significant voltage compartmentalization. Nanopipettes can thus be used to electrically probe biological nanostructures.

Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes

PubMed Central

Jayant, Krishna; Hirtz, Jan J.; Plante, Ilan Jen-La; Tsai, David M.; De Boer, Wieteke D. A. M.; Semonche, Alexa; Peterka, Darcy S.; Owen, Jonathan S.; Sahin, Ozgur; Shepard, Kenneth L.; Yuste, Rafael

2017-01-01

Dendritic spines are the primary site of excitatory synaptic input onto neurons, and are biochemically isolated from the parent dendritic shaft by their thin neck. However, due to the lack of direct electrical recordings from spines, the influence that the neck resistance has on synaptic transmission, and the extent to which spines compartmentalize voltage, specifically excitatory postsynaptic potentials, albeit critical, remains controversial. Here, we use quantum-dot-coated nanopipette electrodes (tip diameters ~15–30 nm) to establish the first intracellular recordings from targeted spine heads under two-photon visualization. Using simultaneous somato-spine electrical recordings, we find that back propagating action potentials fully invade spines, that excitatory postsynaptic potentials are large in the spine head (mean 26 mV) but are strongly attenuated at the soma (0.5–1 mV) and that the estimated neck resistance (mean 420 MΩ) is large enough to generate significant voltage compartmentalization. Nanopipettes can thus be used to electrically probe biological nanostructures. PMID:27941898

Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes.

PubMed

Jayant, Krishna; Hirtz, Jan J; Plante, Ilan Jen-La; Tsai, David M; De Boer, Wieteke D A M; Semonche, Alexa; Peterka, Darcy S; Owen, Jonathan S; Sahin, Ozgur; Shepard, Kenneth L; Yuste, Rafael

2017-05-01

Dendritic spines are the primary site of excitatory synaptic input onto neurons, and are biochemically isolated from the parent dendritic shaft by their thin neck. However, due to the lack of direct electrical recordings from spines, the influence that the neck resistance has on synaptic transmission, and the extent to which spines compartmentalize voltage, specifically excitatory postsynaptic potentials, albeit critical, remains controversial. Here, we use quantum-dot-coated nanopipette electrodes (tip diameters ∼15-30 nm) to establish the first intracellular recordings from targeted spine heads under two-photon visualization. Using simultaneous somato-spine electrical recordings, we find that back propagating action potentials fully invade spines, that excitatory postsynaptic potentials are large in the spine head (mean 26 mV) but are strongly attenuated at the soma (0.5-1 mV) and that the estimated neck resistance (mean 420 MΩ) is large enough to generate significant voltage compartmentalization. Nanopipettes can thus be used to electrically probe biological nanostructures.

Combination of High-density Microelectrode Array and Patch Clamp Recordings to Enable Studies of Multisynaptic Integration.

PubMed

Jäckel, David; Bakkum, Douglas J; Russell, Thomas L; Müller, Jan; Radivojevic, Milos; Frey, Urs; Franke, Felix; Hierlemann, Andreas

2017-04-20

We present a novel, all-electric approach to record and to precisely control the activity of tens of individual presynaptic neurons. The method allows for parallel mapping of the efficacy of multiple synapses and of the resulting dynamics of postsynaptic neurons in a cortical culture. For the measurements, we combine an extracellular high-density microelectrode array, featuring 11'000 electrodes for extracellular recording and stimulation, with intracellular patch-clamp recording. We are able to identify the contributions of individual presynaptic neurons - including inhibitory and excitatory synaptic inputs - to postsynaptic potentials, which enables us to study dendritic integration. Since the electrical stimuli can be controlled at microsecond resolution, our method enables to evoke action potentials at tens of presynaptic cells in precisely orchestrated sequences of high reliability and minimum jitter. We demonstrate the potential of this method by evoking short- and long-term synaptic plasticity through manipulation of multiple synaptic inputs to a specific neuron.

Burst and Principal Components Analyses of MEA Data Separates Chemicals by Class

EPA Science Inventory

Microelectrode arrays (MEAs) detect drug and chemical induced changes in action potential "spikes" in neuronal networks and can be used to screen chemicals for neurotoxicity. Analytical "fingerprinting," using Principal Components Analysis (PCA) on spike trains recorded from prim...

Synaptic potentials recorded by the sucrosegap method from the rabbit superior cervical ganglion

PubMed Central

Kosterlitz, H. W.; Lees, G. M.; Wallis, D. I.

1970-01-01

1. Compound ganglionic potentials evoked by stimulation of the preganglionic nerves to the superior cervical ganglion of the rabbit were recorded by the sucrose-gap method. 2. When the distal part of the ganglion was bathed in flowing isotonic sucrose solution or sodium-deficient solutions, ganglionic action potentials were no longer evoked, only large synaptic potentials. 3. The compound synaptic potential, which remained unaltered for more than 1 h, originated in a population of cells at the interface between the Krebs and sucrose solutions. Hexamethonium reduced the size but did not alter the time course of the synaptic potential. 4. It is suggested that a higher concentration of sodium ions is required for the generation of ganglionic action potentials than for either conduction in the postganglionic axons or production of synaptic potentials. 5. When lithium replaced sodium in the solution bathing the distal part of the ganglion, the synaptic potential was greatly reduced in amplitude. Impulse propagation in the postganglionic axons was only slightly impaired when lithium replaced sodium in the solution bathing the axons. 6. A quantitative assessment of the potency of the ganglion-blocking drugs nicotine, pentolinium, hexamethonium and pempidine was made by measuring the depression of the synaptic potentials produced by bathing the distal part of the ganglion in flowing isotonic sucrose solution. The concentrations which produced a 50% depression were 8·1 μM nicotine, 26·5 μM pentolinium, 111 μM hexamethonium and 22·2 μM pempidine. PMID:5492898

Report of the Tape Recorder Action Plan Committee, 21 March 1972

NASA Technical Reports Server (NTRS)

1972-01-01

A NASA/AF Tape Recorder Action Plan Committee was formed in January 1972 to investigate tape recorder problems and to recommend an action plan to NASA management. The committee collected data on tape recorder failure history, pinpointed problem areas, discussed needed technical and management changes, and proposed an action plan for the recommended approaches.

Superfund record of decision (EPA Region 4): Paducah Gaseous Diffusion Plant (USDOE), Operable Unit 15, Paducah, KY, August 10, 1998

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1998-12-01

This decision document presents the remedial action for the Solid Waste Management Unit (SWMU) 91 of the Waste Area Group (WAG) 27 at the Paducah Gaseous Diffusion Plant (PGDP) near Paducah, Kentucky. The primary objective of this remedial action is to reduce the level of TCE-contaminated soil thereby reducing the potential future concentrations in ground water that could pose a threat to human health and the environment at the POE (i.e., the DOE property boundary). The potential for migration of the contamination from the soil of the off-site aquifer is the concern associated with the SWMU.

Diminished A-type potassium current and altered firing properties in presympathetic PVN neurones in renovascular hypertensive rats

PubMed Central

Sonner, Patrick M; Filosa, Jessica A; Stern, Javier E

2008-01-01

Accumulating evidence supports a contribution of the hypothalamic paraventricular nucleus (PVN) to sympathoexcitation and elevated blood pressure in renovascular hypertension. However, the underlying mechanisms resulting in altered neuronal function in hypertensive rats remain largely unknown. Here, we aimed to address whether the transient outward potassium current (IA) in identified rostral ventrolateral medulla (RVLM)-projecting PVN neurones is altered in hypertensive rats, and whether such changes affected single and repetitive action potential properties and associated changes in intracellular Ca2+ levels. Patch-clamp recordings obtained from PVN-RVLM neurons showed a reduction in IA current magnitude and single channel conductance, and an enhanced steady-state current inactivation in hypertensive rats. Morphometric reconstructions of intracellularly labelled PVN-RVLM neurons showed a diminished dendritic surface area in hypertensive rats. Consistent with a diminished IA availability, action potentials in PVN-RVLM neurons in hypertensive rats were broader, decayed more slowly, and were less sensitive to the K+ channel blocker 4-aminopyridine. Simultaneous patch clamp recordings and confocal Ca2+ imaging demonstrated enhanced action potential-evoked intracellular Ca2+ transients in hypertensive rats. Finally, spike broadening during repetitive firing discharge was enhanced in PVN-RVLM neurons from hypertensive rats. Altogether, our results indicate that diminished IA availability constitutes a contributing mechanism underlying aberrant central neuronal function in renovascular hypertension. PMID:18238809

Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice.

PubMed

Vanacker, Charlotte; Moya, Manuel Ricu; DeFazio, R Anthony; Johnson, Michael L; Moenter, Suzanne M

2017-10-01

Pulsatile release of gonadotropin-releasing hormone (GnRH) is key to fertility. Pulse frequency is modulated by gonadal steroids and likely arises subsequent to coordination of GnRH neuron firing activity. The source of rhythm generation and the site of steroid feedback remain critical unanswered questions. Arcuate neurons that synthesize kisspeptin, neurokinin B, and dynorphin (KNDy) may be involved in both of these processes. We tested the hypotheses that action potential firing in KNDy neurons is episodic and that gonadal steroids regulate this pattern. Targeted extracellular recordings were made of green fluorescent protein-identified KNDy neurons in brain slices from adult male mice that were intact, castrated, or castrated and treated with estradiol or dihydrotestosterone (DHT). KNDy neurons exhibited marked peaks and nadirs in action potential firing activity during recordings lasting 1 to 3.5 hours. Peaks, identified by Cluster analysis, occurred more frequently in castrated than intact mice, and either estradiol or DHT in vivo or blocking neurokinin type 3 receptor in vitro restored peak frequency to intact levels. The frequency of peaks in firing rate and estradiol regulation of this frequency is similar to that observed for GnRH neurons, whereas DHT suppressed firing in KNDy but not GnRH neurons. We further examined the patterning of action potentials to identify bursts that may be associated with increased neuromodulator release. Burst frequency and duration are increased in castrated compared with intact and steroid-treated mice. The observation that KNDy neurons fire in an episodic manner that is regulated by steroid feedback is consistent with a role for these neurons in GnRH pulse generation and regulation. Copyright © 2017 Endocrine Society.

Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

PubMed

Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

2017-05-24

Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of cellular output to the locations that receive most input: the dendrites. In thalamocortical and thalamic reticular nucleus neurons, the site of AP generation and the true extent of backpropagation remain unknown. Using patch-clamp recordings, this study measures dendritic propagation of APs directly in these neurons. In either cell type, high-frequency low-threshold spike burst or lower-frequency tonic APs undergo substantial voltage attenuation as they spread into the dendritic tree. Therefore, backpropagating spikes in these cells can only influence signaling in the proximal part of the dendritic tree. Copyright © 2017 Connelly et al.

A novel framework for feature extraction in multi-sensor action potential sorting.

PubMed

Wu, Shun-Chi; Swindlehurst, A Lee; Nenadic, Zoran

2015-09-30

Extracellular recordings of multi-unit neural activity have become indispensable in neuroscience research. The analysis of the recordings begins with the detection of the action potentials (APs), followed by a classification step where each AP is associated with a given neural source. A feature extraction step is required prior to classification in order to reduce the dimensionality of the data and the impact of noise, allowing source clustering algorithms to work more efficiently. In this paper, we propose a novel framework for multi-sensor AP feature extraction based on the so-called Matched Subspace Detector (MSD), which is shown to be a natural generalization of standard single-sensor algorithms. Clustering using both simulated data and real AP recordings taken in the locust antennal lobe demonstrates that the proposed approach yields features that are discriminatory and lead to promising results. Unlike existing methods, the proposed algorithm finds joint spatio-temporal feature vectors that match the dominant subspace observed in the two-dimensional data without needs for a forward propagation model and AP templates. The proposed MSD approach provides more discriminatory features for unsupervised AP sorting applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimulus-dependent deliberation process leading to a specific motor action demonstrated via a multi-channel EEG analysis

PubMed Central

Henz, Sonja; Kutz, Dieter F.; Werner, Jana; Hürster, Walter; Kolb, Florian P.; Nida-Ruemelin, Julian

2015-01-01

The aim of the study was to determine whether a deliberative process, leading to a motor action, is detectable in high density EEG recordings. Subjects were required to press one of two buttons. In a simple motor task the subject knew which button to press, whilst in a color-word Stroop task subjects had to press the right button with the right index finger when meaning and color coincided, or the left button with the left index finger when meaning and color were disparate. EEG recordings obtained during the simple motor task showed a sequence of positive (P) and negative (N) cortical potentials (P1-N1-P2) which are assumed to be related to the processing of the movement. The sequence of cortical potentials was similar in EEG recordings of subjects having to deliberate over how to respond, but the above sequence (P1-N1-P2) was preceded by slowly increasing negativity (N0), with N0 being assumed to represent the end of the deliberation process. Our data suggest the existence of neurophysiological correlates of deliberative processes. PMID:26190987

Challenges of Identifying Clinically Actionable Genetic Variants for Precision Medicine

PubMed Central

2016-01-01

Advances in genomic medicine have the potential to change the way we treat human disease, but translating these advances into reality for improving healthcare outcomes depends essentially on our ability to discover disease- and/or drug-associated clinically actionable genetic mutations. Integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a big data infrastructure can provide an efficient and effective way to identify clinically actionable genetic variants for personalized treatments and reduce healthcare costs. We review bioinformatics processing of next-generation sequencing (NGS) data, bioinformatics infrastructures for implementing precision medicine, and bioinformatics approaches for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs. PMID:27195526

A Low-Cost Multielectrode System for Data Acquisition Enabling Real-Time Closed-Loop Processing with Rapid Recovery from Stimulation Artifacts

PubMed Central

Rolston, John D.; Gross, Robert E.; Potter, Steve M.

2009-01-01

Commercially available data acquisition systems for multielectrode recording from freely moving animals are expensive, often rely on proprietary software, and do not provide detailed, modifiable circuit schematics. When used in conjunction with electrical stimulation, they are prone to prolonged, saturating stimulation artifacts that prevent the recording of short-latency evoked responses. Yet electrical stimulation is integral to many experimental designs, and critical for emerging brain-computer interfacing and neuroprosthetic applications. To address these issues, we developed an easy-to-use, modifiable, and inexpensive system for multielectrode neural recording and stimulation. Setup costs are less than US$10,000 for 64 channels, an order of magnitude lower than comparable commercial systems. Unlike commercial equipment, the system recovers rapidly from stimulation and allows short-latency action potentials (<1 ms post-stimulus) to be detected, facilitating closed-loop applications and exposing neural activity that would otherwise remain hidden. To illustrate this capability, evoked activity from microstimulation of the rodent hippocampus is presented. System noise levels are similar to existing platforms, and extracellular action potentials and local field potentials can be recorded simultaneously. The system is modular, in banks of 16 channels, and flexible in usage: while primarily designed for in vivo use, it can be combined with commercial preamplifiers to record from in vitro multielectrode arrays. The system's open-source control software, NeuroRighter, is implemented in C#, with an easy-to-use graphical interface. As C# functions in a managed code environment, which may impact performance, analysis was conducted to ensure comparable speed to C++ for this application. Hardware schematics, layout files, and software are freely available. Since maintaining wired headstage connections with freely moving animals is difficult, we describe a new method of electrode-headstage coupling using neodymium magnets. PMID:19668698

Action potential broadening in a presynaptic channelopathy

NASA Astrophysics Data System (ADS)

Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

2016-07-01

Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

Bio-amplifier with Driven Shield Inputs to Reduce Electrical Noise and its Application to Laboratory Teaching of Electrophysiology

PubMed Central

Matsuzaka, Yoshiya; Ichihara, Toshiaki; Abe, Toshihiko; Mushiake, Hajime

2012-01-01

We describe a custom-designed bio-amplifier and its use in teaching neurophysiology to undergraduate students. The amplifier has the following features: 1) differential amplification with driven shield inputs, which makes it workable even in electrically unshielded environments, 2) high input impedance to allow recordings of small signals through high signal source impedance, 3) dual fixed frequency bandpass filters (1–340Hz for surface EMG, EEG, local field potential etc and 320Hz – 3.4kHz for neuronal action potential recording) and independent gain controllers (up to x107,000) to allow the recording of different signals from the same source (e.g., local field potential and spiking activity of neurons), and 4) printed circuit board technology for easy replication with consistent quality. We compared its performance with a commercial amplifier in an electrically noisy environment. Even without any electrostatic shield, it recorded clear electromyographic activity with little interference from other electric appliances. In contrast, the commercial amplifier’s performance severely deteriorated under the same condition. We used this amplifier to build a computer-controlled stimulation and measurement system for electroencephalographic recordings by undergraduate students. The students successfully recorded various sensory evoked potentials with clarity that otherwise would have required costly instruments. This amplifier is a low-cost yet reliable instrument for electro-physiological recording both in education and research. PMID:23504543

Extracellular K+ in the supraoptic nucleus of the rat during reflex bursting activity by oxytocin neurones.

PubMed Central

Coles, J A; Poulain, D A

1991-01-01

1. We have investigated changes in extracellular potassium concentration [K+]o in the supraoptic nucleus of lactating rats and in particular those that occur during the intense burst of firing by the oxytocin neurones involved in the milk ejection reflex. 2. Double-barrelled K(+)-selective microelectrodes containing a highly selective sensor based on valinomycin were lowered through the exposed cortex towards the supraoptic nucleus (SON) of female rats anaesthetized with urethane. The mean resting [K+]o in the hypothalami of five rats was 2.4 mM, S.D. = 0.3 mM. 3. Where the reference barrel recorded extracellular action potentials from an oxytocin cell, the reflex burst of firing (4 s, typical maximum 50 Hz) was accompanied by a mean increase in [K+]o (delta[K+]o) of 0.22 mM (S.E.M. = 0.02 mM, fifty-seven bursts in eight cells in seven rats). The rise in [K+]o did not begin more than 0.1 s before the onset of the burst, and began to fall from its maximum during the burst. Slow field potentials, indicative of spatial buffering of K+, were undetectable (less than 50 microV). When the electrode was advanced in steps, the amplitudes of both delta[K+]o and the action potential declined steeply to about 10% over a distance of 20 microns: K+ from oxytocin cells appears to be prevented from dispersing freely through the extracellular space of the SON. 4. When the electrode recorded action potentials from a vasopressin cell, delta[K+]o during an oxytocin cell burst was very small: 0.021 mM (S.E.M. = 0.005 mM). At other sites in the SON, where antidromic stimulation evoked a field potential but no action potential, delta[K+]o was 0.047 +/- 0.005 mM. We conclude that the reason oxytocin bursts do not affect vasopressin cells is that [K+]o rises very little around vasopressin cells. A fortiori, since the increases in [K+]o were very small except where action potentials from oxytocin cells were recorded, they can make no significant contribution to synchronizing the onsets of bursts in oxytocin cells that are not contiguous. 5. A standard antidromic stimulation from the pituitary stalk, at 40 Hz for 4 s, which stimulated both oxytocin neurones and vasopressin neurones, caused a delta[K+]o of 0.17-1.8 mM, the variation being mainly from rat to rat. The larger delta[K+]o values were accompanied by slow negative potentials of up to 1.5 mV, there was a gradient in delta[K+]o decreasing towards the pia at the inferior limit of the SON, and there was a slow increase in [K+] in the subarachnoid space.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1895242

48 CFR 1450.101-3 - Records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Records. 1450.101-3... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.101-3 Records. The records of actions taken under FAR Part 50 shall be maintained by the Director, PAM. ...

48 CFR 1450.101-3 - Records.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Records. 1450.101-3... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.101-3 Records. The records of actions taken under FAR Part 50 shall be maintained by the Director, PAM. ...

48 CFR 1450.101-3 - Records.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Records. 1450.101-3... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.101-3 Records. The records of actions taken under FAR Part 50 shall be maintained by the Director, PAM. ...

48 CFR 1450.101-3 - Records.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Records. 1450.101-3... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.101-3 Records. The records of actions taken under FAR Part 50 shall be maintained by the Director, PAM. ...

Action prediction based on anticipatory brain potentials during simulated driving.

PubMed

Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R

2015-12-01

The ability of an automobile to infer the driver's upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver's intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by 'Start'/'Stop' cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a 'Red' traffic light) versus events that do not require such action (No-go condition; e.g. a 'Yellow' light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. We show for the first time the feasibility of predicting the driver's intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.

2005-04-15

The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na{sub v}) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na{sub v} channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons,more » P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na{sub v} currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na{sub v} channel gating, observed clinically in response to ciguatera poisoning.« less

Electrically evoked compound action potentials are different depending on the site of cochlear stimulation.

PubMed

van de Heyning, Paul; Arauz, Santiago L; Atlas, Marcus; Baumgartner, Wolf-Dieter; Caversaccio, Marco; Chester-Browne, Ronel; Estienne, Patricia; Gavilan, Javier; Godey, Benoit; Gstöttner, Wolfgang; Han, Demin; Hagen, Rudolph; Kompis, Martin; Kuzovkov, Vlad; Lassaletta, Luis; Lefevre, Franc; Li, Yongxin; Müller, Joachim; Parnes, Lorne; Kleine Punte, Andrea; Raine, Christopher; Rajan, Gunesh; Rivas, Adriana; Rivas, José Antonio; Royle, Nicola; Sprinzl, Georg; Stephan, Kurt; Walkowiak, Adam; Yanov, Yuri; Zimmermann, Kim; Zorowka, Patrick; Skarzynski, Henryk

2016-11-01

One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEX SOFT electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties.

A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology

PubMed Central

Márton, Gergely; Orbán, Gábor; Kiss, Marcell; Fiáth, Richárd; Pongrácz, Anita; Ulbert, István

2015-01-01

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks. PMID:26683306

The science of neural interface systems.

PubMed

Hatsopoulos, Nicholas G; Donoghue, John P

2009-01-01

The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.

A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology.

PubMed

Márton, Gergely; Orbán, Gábor; Kiss, Marcell; Fiáth, Richárd; Pongrácz, Anita; Ulbert, István

2015-01-01

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks.

Influence of asymmetric attenuation of single and paired dendritic inputs on summation of synaptic potentials and initiation of action potentials.

PubMed

Fortier, Pierre A; Bray, Chelsea

2013-04-16

Previous studies revealed mechanisms of dendritic inputs leading to action potential initiation at the axon initial segment and backpropagation into the dendritic tree. This interest has recently expanded toward the communication between different parts of the dendritic tree which could preprocess information before reaching the soma. This study tested for effects of asymmetric voltage attenuation between different sites in the dendritic tree on summation of synaptic inputs and action potential initiation using the NEURON simulation environment. Passive responses due to the electrical equivalent circuit of the three-dimensional neuron architecture with leak channels were examined first, followed by the responses after adding voltage-gated channels and finally synaptic noise. Asymmetric attenuation of voltage, which is a function of asymmetric input resistance, was seen between all pairs of dendritic sites but the transfer voltages (voltage recorded at the opposite site from stimulation among a pair of dendritic sites) were equal and also summed linearly with local voltage responses during simultaneous stimulation of both sites. In neurons with voltage-gated channels, we reproduced the observations where a brief stimulus to the proximal ascending dendritic branch of a pyramidal cell triggers a local action potential but a long stimulus triggers a somal action potential. Combined stimulation of a pair of sites in this proximal dendrite did not alter this pattern. The attraction of the action potential onset toward the soma with a long stimulus in the absence of noise was due to the higher density of voltage-gated sodium channels at the axon initial segment. This attraction was, however, negligible at the most remote distal dendritic sites and was replaced by an effect due to high input resistance. Action potential onset occurred at the dendritic site of higher input resistance among a pair of remote dendritic sites, irrespective of which of these two sites received the synaptic input. Exploration of the parameter space showed how the gradient of voltage-gated channel densities and input resistances along a dendrite could draw the action potential onset away from the stimulation site. The attraction of action potential onset toward the higher density of voltage-gated channels in the soma during stimulation of the proximal dendrite was, however, reduced after the addition of synaptic noise. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Long term in vitro stability of fully integrated wireless neural interfaces based on Utah slant electrode array

NASA Astrophysics Data System (ADS)

Sharma, Asha; Rieth, Loren; Tathireddy, Prashant; Harrison, Reid; Solzbacher, Florian

2010-02-01

We herein report in vitro functional stability and recording longevity of a fully integrated wireless neural interface (INI). The INI uses biocompatible Parylene-C as an encapsulation layer, and was immersed in phosphate buffered saline (PBS) for a period of over 150 days. The full functionality (wireless radio-frequency power, command, and signal transmission) and the ability of INI to record artificial action potentials even after 150 days of PBS soaking without any change in signal/noise amplitude constitutes a major milestone in long term stability, and evaluate the encapsulation reliability, functional stability, and potential usefulness for future chronic implants.

41 CFR 60-2.32 - Affirmative action records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Affirmative action records. 60-2.32 Section 60-2.32 Public Contracts and Property Management Other Provisions Relating to... OF LABOR 2-AFFIRMATIVE ACTION PROGRAMS Miscellaneous § 60-2.32 Affirmative action records. The...

41 CFR 60-2.32 - Affirmative action records.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 41 Public Contracts and Property Management 1 2011-07-01 2009-07-01 true Affirmative action records. 60-2.32 Section 60-2.32 Public Contracts and Property Management Other Provisions Relating to... OF LABOR 2-AFFIRMATIVE ACTION PROGRAMS Miscellaneous § 60-2.32 Affirmative action records. The...

Spatial variability in T-tubule and electrical remodeling of left ventricular epicardium in mouse hearts with transgenic Gαq overexpression-induced pathological hypertrophy

PubMed Central

Tao, Wen; Shi, Jianjian; Dorn, Gerald W.; Wei, Lei; Rubart, Michael

2012-01-01

Pathological left ventricular hypertrophy (LVH) is consistently associated with prolongation of the ventricular action potentials. A number of previous studies, employing various experimental models of hypertrophy, have revealed marked differences in the effects of hypertrophy on action potential duration (APD) between myocytes from endocardial and epicardial layers of the LV free wall. It is not known, however, whether pathological LVH is also accompanied by redistribution of APD among myocytes from the same layer in the LV free wall. In the experiments here, LV epicardial action potential remodeling was examined in a mouse model of decompensated LVH, produced by cardiac-restricted transgenic Gαq overexpression. Confocal linescanning-based optical recordings of propagated action potentials from individual in situ cardiomyocytes across the outer layer of the anterior LV epicardium demonstrated spatially non-uniform action potential prolongation in transgenic hearts, giving rise to alterations in spatial dispersion of epicardial repolarization. Local density and distribution of anti-Cx43 mmune reactivity in Gαq hearts were unchanged compared to wild-type hearts, suggesting preservation of intercellular coupling. Confocal microscopy also revealed heterogeneous disorganization of T-tubules in epicardial cardiomyocytes in situ. These data provide evidence of the existence of significant electrical and structural heterogeneity within the LV epicardial layer of hearts with transgenic Gαq overexpression-induced hypertrophy, and further support the notion that a small portion of electrically well connected LV tissue can maintain dispersion of action potential duration through heterogeneity in the activities of sarcolemmal ionic currents that control repolarization. It remains to be examined whether other experimental models of pathological LVH, including pressure overload LVH, similarly exhibit alterations in T-tubule organization and/or dispersion of repolarization within distinct layers of LV myocardium. PMID:22728217

Voltage-gated currents in identified rat olfactory receptor neurons.

PubMed

Trombley, P Q; Westbrook, G L

1991-02-01

Whole-cell recording techniques were used to characterize voltage-gated membrane currents in neonatal rat olfactory receptor neurons (ORNs) in cell culture. Mature ORNs were identified in culture by their characteristic bipolar morphology, by retrograde labeling techniques, and by olfactory marker protein (OMP) immunoreactivity. ORNs did not have spontaneous activity, but fired action potentials to depolarizing current pulses. Action potentials were blocked by tetrodotoxin (TTX), which contrasts with the TTX-resistant action potentials in salamander olfactory receptor cells (e.g., Firestein and Werblin, 1987). Prolonged, suprathreshold current pulses evoked only a single action potential; however, repetitive firing up to 35 Hz could be elicited by a series of brief depolarizing pulses. Under voltage clamp, the TTX-sensitive sodium current had activation and inactivation properties similar to other excitable cells. In TTX and 20 mM barium, sustained inward current were evoked by voltage steps positive to -30 mV. This current was blocked by Cd (100 microM) and by nifedipine (IC50 = 368 nM) consistent with L-type calcium channels in other neurons. No T-type calcium current was observed. Voltage steps positive to -20 mV also evoked an outward current that did not inactivate during 100-msec depolarizations. Tail current analysis of this current was consistent with a selective potassium conductance. The outward current was blocked by external tetraethylammonium but was unaffected by Cd or 4-aminopyridine (4-AP) or by removal of external calcium. A transient outward current was not observed. The 3 voltage-dependent conductances in cultured rat ORNs appear to be sufficient for 2 essential functions: action potential generation and transmitter release. As a single odorant-activated channel can trigger an action potential (e.g., Lynch and Barry, 1989), the repetitive firing seen with brief depolarizing pulses suggests that ORNs do not integrate sensory input, but rather act as high-fidelity relays such that each opening of an odorant-activated channel reaches the olfactory bulb glomeruli as an action potential.

Modulation of the Intracortical LFP during Action Execution and Observation

PubMed Central

Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N.; Kraskov, Alexander

2015-01-01

The activity of mirror neurons in macaque ventral premotor cortex (PMv) and primary motor cortex (M1) is modulated by the observation of another's movements. This modulation could underpin well documented changes in EEG/MEG activity indicating the existence of a mirror neuron system in humans. Because the local field potential (LFP) represents an important link between macaque single neuron and human noninvasive studies, we focused on mirror properties of intracortical LFPs recorded in the PMv and M1 hand regions in two macaques while they reached, grasped and held different objects, or observed the same actions performed by an experimenter. Upper limb EMGs were recorded to control for covert muscle activity during observation. The movement-related potential (MRP), investigated as intracortical low-frequency LFP activity (<9 Hz), was modulated in both M1 and PMv, not only during action execution but also during action observation. Moreover, the temporal LFP modulations during execution and observation were highly correlated in both cortical areas. Beta power in both PMv and M1 was clearly modulated in both conditions. Although the MRP was detected only during dynamic periods of the task (reach/grasp/release), beta decreased during dynamic and increased during static periods (hold). Comparison of LFPs for different grasps provided evidence for partially nonoverlapping networks being active during execution and observation, which might be related to different inputs to motor areas during these conditions. We found substantial information about grasp in the MRP corroborating its suitability for brain–machine interfaces, although information about grasp was generally low during action observation. PMID:26041914

Characterization of Early Cortical Neural Network Development in Multiwell Microelectrode Array Plates

EPA Science Inventory

We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentiall...

Understanding approach and avoidance in verbal descriptions of everyday actions: An ERP study.

PubMed

Marrero, Hipólito; Urrutia, Mabel; Beltrán, David; Gámez, Elena; Díaz, José M

2017-06-01

Understanding verbal descriptions of everyday actions could involve the neural representation of action direction (avoidance and approach) toward persons and things. We recorded the electrophysiological activity of participants while they were reading approach/avoidance action sentences that were directed toward a target: a thing/a person (i.e., "Petra accepted/rejected Ramón in her group"/ "Petra accepted/rejected the receipt of the bank"). We measured brain potentials time locked to the target word. In the case of things, we found a N400-like component with right frontal distribution modulated by approach/avoidance action. This component was more negative in avoidance than in approach sentences. In the case of persons, a later negative event-related potential (545-750 ms) with left frontal distribution was sensitive to verb direction, showing more negative amplitude for approach than avoidance actions. In addition, more negativity in approach-person sentences was associated with fear avoidance trait, whereas less negativity in avoidance-person sentences was associated with a greater approach trait. Our results support that verbal descriptions of approach/avoidance actions are encoded differently depending on whether the target is a thing or a person. Implications of these results for a social, emotional and motivational understanding of action language are discussed.

A two-channel action-potential generator for testing neurophysiologic data acquisition/analysis systems.

PubMed

Lisiecki, R S; Voigt, H F

1995-08-01

A 2-channel action-potential generator system was designed for use in testing neurophysiologic data acquisition/analysis systems. The system consists of a personal computer controlling an external hardware unit. This system is capable of generating 2 channels of simulated action potential (AP) waveshapes. The AP waveforms are generated from the linear combination of 2 principal-component template functions. Each channel generates randomly occurring APs with a specified rate ranging from 1 to 200 events per second. The 2 trains may be independent of one another or the second channel may be made to be excited or inhibited by the events from the first channel with user-specified probabilities. A third internal channel may be made to excite or inhibit events in both of the 2 output channels with user-specified rate parameters and probabilities. The system produces voltage waveforms that may be used to test neurophysiologic data acquisition systems for recording from 2 spike trains simultaneously and for testing multispike-train analysis (e.g., cross-correlation) software.

Nobody Is Perfect: ERP Effects Prior to Performance Errors in Musicians Indicate Fast Monitoring Processes

PubMed Central

Maidhof, Clemens; Rieger, Martina; Prinz, Wolfgang; Koelsch, Stefan

2009-01-01

Background One central question in the context of motor control and action monitoring is at what point in time errors can be detected. Previous electrophysiological studies investigating this issue focused on brain potentials elicited after erroneous responses, mainly in simple speeded response tasks. In the present study, we investigated brain potentials before the commission of errors in a natural and complex situation. Methodology/Principal Findings Expert pianists bimanually played scales and patterns while the electroencephalogram (EEG) was recorded. Event-related potentials (ERPs) were computed for correct and incorrect performances. Results revealed differences already 100 ms prior to the onset of a note (i.e., prior to auditory feedback). We further observed that erroneous keystrokes were delayed in time and pressed more slowly. Conclusions Our data reveal neural mechanisms in musicians that are able to detect errors prior to the execution of erroneous movements. The underlying mechanism probably relies on predictive control processes that compare the predicted outcome of an action with the action goal. PMID:19337379

Activity-dependent modulation of the axonal conduction of action potentials along rat hippocampal mossy fibers.

PubMed

Chida, Kuniaki; Kaneko, Kenya; Fujii, Satoshi; Yamazaki, Yoshihiko

2015-01-01

The axonal conduction of action potentials in the nervous system is generally considered to be a stable signal for the relaying of information, and its dysfunction is involved in impairment of cognitive function. Recent evidence suggests that the conduction properties and excitability of axons are more variable than traditionally thought. To investigate possible changes in the conduction of action potentials along axons in the central nervous system, we recorded action potentials from granule cells that were evoked and conducted antidromically along unmyelinated mossy fibers in the rat hippocampus. To evaluate changes in axons by eliminating any involvement of changes in the somata, two latency values were obtained by stimulating at two different positions and the latency difference between the action potentials was measured. A conditioning electrical stimulus of 20 pulses at 1 Hz increased the latency difference and this effect, which lasted for approximately 30 s, was inhibited by the application of an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist or a GluK1-containing kainate receptor antagonist, but not by an AMPA receptor-selective antagonist or an N-methyl-d-aspartate receptor antagonist. These results indicated that axonal conduction in mossy fibers is modulated in an activity-dependent manner through the activation of GluK1-containing kainate receptors. These dynamic changes in axonal conduction may contribute to the physiology and pathophysiology of the brain. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

48 CFR 50.101-3 - Records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Records. 50.101-3 Section... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.101-3 Records. Agencies shall maintain complete records of all actions taken under this Subpart 50.1. For each request for...

48 CFR 50.101-3 - Records.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Records. 50.101-3 Section... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.101-3 Records. Agencies shall maintain complete records of all actions taken under this Subpart 50.1. For each request for...

48 CFR 50.101-3 - Records.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Records. 50.101-3 Section... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.101-3 Records. Agencies shall maintain complete records of all actions taken under this Subpart 50.1. For each request for...

48 CFR 50.101-3 - Records.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Records. 50.101-3 Section... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.101-3 Records. Agencies shall maintain complete records of all actions taken under this Subpart 50.1. For each request for...

The effects of substance P on smooth muscle cells and on neuro-effector transmission in the guinea-pig ileum

PubMed Central

Fujisawa, Kazuaki; Ito, Yushi

1982-01-01

1 The effects of substance P (SP) on the membrane and contractile properties of the smooth muscle cell, or on neuro-effector transmission in the guinea-pig ileum were observed by means of microelectrodes, double sucrose gap and tension recording. 2 SP (10-13-10-10M) induced a phasic contraction of longitudinal muscle strips, but did not change the muscle tone of circular muscle strips, in concentrations up to 10-8M. 3 SP (10-10-10-8M) evoked three different membrane responses in longitudinal muscle cells: (i) bursts of spike discharges with no significant change in the membrane potential and input membrane resistance; (ii) bursts of spike discharges with a small but clear depolarization of the membrane and increase in the input membrane resistance; (iii) slow waves with no change in the membrane potential. 4 In the circular muscle cells, low concentrations of SP (<10-8M) did not affect the membrane potential or the spikes, but SP (10-7M) increased the spike discharges with no significant change in the membrane potential. 5 SP (10-10M) reduced the threshold depolarization required for the generation of action potentials with no change in membrane potential of the longitudinal muscle cells. 6 Pretreatment with atropine (5 × 10-6M), tetrodotoxin (TTX 10-6M) or baclofen (4.7 × 10-6M) had no effect on the excitatory actions of SP on the smooth muscle cells of longitudinal and circular muscle strips. 7 Excitatory actions of SP on the membrane potential or spike activities of longitudinal muscle cells were preserved in NaCl but not in Ca-deficient solution. 8 SP (10-10-10-9M) enhanced the amplitude of the excitatory junction potentials (e.j.ps) evoked by electrical field stimulation in longitudinal muscle cells with no change in the membrane potential and input resistance. SP (10-10-10-9M), however, did not change the amplitude of inhibitory junction potentials (i.j.ps) recorded from the circular muscle cells. 9 These results indicate that SP in relatively low concentrations acts on both smooth muscle cells and on excitatory neuro-effector transmission in the longitudinal muscle; the main site of the action of SP is probably the muscle membrane. PMID:6178458

Axonal GABAA receptors.

PubMed

Trigo, Federico F; Marty, Alain; Stell, Brandon M

2008-09-01

Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

A four-component model of the action potential in mouse detrusor smooth muscle cell

PubMed Central

Brain, Keith L.; Young, John S.; Manchanda, Rohit

2018-01-01

Background and hypothesis Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known. To address these questions, the basic components which constitute the sAPs were investigated. We hypothesized that linear combinations of scaled versions of these basic components can produce sAP shapes observed in the syncytium. Methods and results The basic components were identified as spontaneous evoked junction potentials (sEJP), native AP (nAP), slow after hyperpolarization (sAHP) and very slow after hyperpolarization (vsAHP). The experimental recordings were grouped into two sets: a training data set and a testing data set. A training set was used to estimate the components, and a test set to evaluate the efficiency of the estimated components. We found that a linear combination of the identified components when appropriately amplified and time shifted replicated various AP shapes to a high degree of similarity, as quantified by the root mean square error (RMSE) measure. Conclusions We conclude that the four basic components—sEJP, nAP, sAHP, and vsAHP—identified and isolated in this work are necessary and sufficient to replicate all varieties of the sAPs recorded experimentally in DSMCs. This model has the potential to generate testable hypotheses that can help identify the physiological processes underlying various features of the sAPs. Further, this model also provides a means to classify the sAPs into various shape classes. PMID:29351282

A four-component model of the action potential in mouse detrusor smooth muscle cell.

PubMed

Padmakumar, Mithun; Brain, Keith L; Young, John S; Manchanda, Rohit

2018-01-01

Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known. To address these questions, the basic components which constitute the sAPs were investigated. We hypothesized that linear combinations of scaled versions of these basic components can produce sAP shapes observed in the syncytium. The basic components were identified as spontaneous evoked junction potentials (sEJP), native AP (nAP), slow after hyperpolarization (sAHP) and very slow after hyperpolarization (vsAHP). The experimental recordings were grouped into two sets: a training data set and a testing data set. A training set was used to estimate the components, and a test set to evaluate the efficiency of the estimated components. We found that a linear combination of the identified components when appropriately amplified and time shifted replicated various AP shapes to a high degree of similarity, as quantified by the root mean square error (RMSE) measure. We conclude that the four basic components-sEJP, nAP, sAHP, and vsAHP-identified and isolated in this work are necessary and sufficient to replicate all varieties of the sAPs recorded experimentally in DSMCs. This model has the potential to generate testable hypotheses that can help identify the physiological processes underlying various features of the sAPs. Further, this model also provides a means to classify the sAPs into various shape classes.

Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

PubMed

Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

2016-05-01

High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS-toxic concentrations, lidocaine unmasked in thalamocortical neurons evoked HT action potentials mediated by the L-type Ca current while substantially suppressing Na-dependent excitability. On the basis of the known role of an increase in intracellular Ca in the pathogenesis of local anesthetic neurotoxicity, this novel action represents a plausible contributing candidate mechanism for lidocaine's CNS toxicity in vivo.

Nanostructured cavity devices for extracellular stimulation of HL-1 cells

NASA Astrophysics Data System (ADS)

Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

2015-05-01

Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network. Electronic supplementary information (ESI) available: Comparison of non-filtered and Savitzky-Golay filtered action potential recordings, electrical signals and corresponding optical signals. See DOI: 10.1039/c5nr01690h

Corrective Action Investigation Plan for Corrective Action Unit 516: Septic Systems and Discharge Points, Nevada Test Site, Nevada, Rev. 0, Including Record of Technical Change No. 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

This Corrective Action Investigation Plan (CAIP) contains the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Sites Office's (NNSA/NSO's) approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 516, Septic Systems and Discharge Points, Nevada Test Site (NTS), Nevada, under the Federal Facility Agreement and Consent Order. CAU 516 consists of six Corrective Action Sites: 03-59-01, Building 3C-36 Septic System; 03-59-02, Building 3C-45 Septic System; 06-51-01, Sump Piping, 06-51-02, Clay Pipe and Debris; 06-51-03, Clean Out Box and Piping; and 22-19-04, Vehicle Decontamination Area. Located in Areasmore » 3, 6, and 22 of the NTS, CAU 516 is being investigated because disposed waste may be present without appropriate controls, and hazardous and/or radioactive constituents may be present or migrating at concentrations and locations that could potentially pose a threat to human health and the environment. Existing information and process knowledge on the expected nature and extent of contamination of CAU 516 are insufficient to select preferred corrective action alternatives; therefore, additional information will be obtained by conducting a corrective action investigation. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document. Record of Technical Change No. 1 is dated 3/2004.« less

Ionic channels underlying the ventricular action potential in zebrafish embryo.

PubMed

Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

2014-06-01

Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson's disease.

PubMed

Melloni, Margherita; Sedeño, Lucas; Hesse, Eugenia; García-Cordero, Indira; Mikulan, Ezequiel; Plastino, Angelo; Marcotti, Aida; López, José David; Bustamante, Catalina; Lopera, Francisco; Pineda, David; García, Adolfo M; Manes, Facundo; Trujillo, Natalia; Ibáñez, Agustín

2015-07-08

Impairments of action language have been documented in early stage Parkinson's disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies.

Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons.

PubMed

Brown, Maile R; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H; Kaczmarek, Leonard K

2016-07-01

Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express "high threshold" voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders. Copyright © 2016 the American Physiological Society.

Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons

PubMed Central

Brown, Maile R.; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H.

2016-01-01

Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express “high threshold” voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders. PMID:27052580

Measuring Dynamic Kidney Function in an Undergraduate Physiology Laboratory

ERIC Educational Resources Information Center

Medler, Scott; Harrington, Frederick

2013-01-01

Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on…

Real-time estimation and biofeedback of single-neuron firing rates using local field potentials

PubMed Central

Hall, Thomas M.; Nazarpour, Kianoush; Jackson, Andrew

2014-01-01

The long-term stability and low-frequency composition of local field potentials (LFPs) offer important advantages for robust and efficient neuroprostheses. However, cortical LFPs recorded by multi-electrode arrays are often assumed to contain only redundant information arising from the activity of large neuronal populations. Here we show that multichannel LFPs in monkey motor cortex each contain a slightly different mixture of distinctive slow potentials that accompany neuronal firing. As a result, the firing rates of individual neurons can be estimated with surprising accuracy. We implemented this method in a real-time biofeedback brain–machine interface, and found that monkeys could learn to modulate the activity of arbitrary neurons using feedback derived solely from LFPs. These findings provide a principled method for monitoring individual neurons without long-term recording of action potentials. PMID:25394574

25 CFR 700.273 - Request for notification of existence of records: Action on.

Code of Federal Regulations, 2010 CFR

2010-04-01

... records were compiled in reasonable anticipation of a civil action or proceeding or (ii) the system of.... (2) If the records were compiled in reasonable anticipation of a civil action or proceeding or the...

36 CFR 1008.12 - Requests for notification of existence of records: Action on.

Code of Federal Regulations, 2010 CFR

2010-07-01

...: (i) The records were compiled in reasonable anticipation of a civil action or proceeding; or (ii) The... rulemaking. (2) If the records were compiled in reasonable anticipation of a civil action or proceeding or...

Leptin alters somatosensory thalamic networks by decreasing gaba release from reticular thalamic nucleus and action potential frequency at ventrobasal neurons.

PubMed

Perissinotti, Paula P; Rivero-Echeto, María Celeste; Garcia-Rill, Edgar; Bisagno, Verónica; Urbano, Francisco J

2018-06-01

Leptin is an adipose-derived hormone that controls appetite and energy expenditure. Leptin receptors are expressed on extra-hypothalamic ventrobasal (VB) and reticular thalamic (RTN) nuclei from embryonic stages. Here, we studied the effects of pressure-puff, local application of leptin on both synaptic transmission and action potential properties of thalamic neurons in thalamocortical slices. We used whole-cell patch-clamp recordings of thalamocortical VB neurons from wild-type (WT) and leptin-deficient obese (ob/ob) mice. We observed differences in VB neurons action potentials and synaptic currents kinetics when comparing WT vs. ob/ob. Leptin reduced GABA release onto VB neurons throughout the activation of a JAK2-dependent pathway, without affecting excitatory glutamate transmission. We observed a rapid and reversible reduction by leptin of the number of action potentials of VB neurons via the activation of large conductance Ca 2+ -dependent potassium channels. These leptin effects were observed in thalamocortical slices from up to 5-week-old WT but not in leptin-deficient obese mice. Results described here suggest the existence of a leptin-mediated trophic modulation of thalamocortical excitability during postnatal development. These findings could contribute to a better understanding of leptin within the thalamocortical system and sleep deficits in obesity.

Electrophysiological evidence of doubly innervated branched muscle fibers in the human brachioradialis muscle.

PubMed

Lateva, Zoia C; McGill, Kevin C

2007-12-01

Motor-unit action potentials (MUAPs) with unstable satellite (late-latency) components are found in EMG signals from the brachioradialis muscles of normal subjects. We analyzed the morphology and blocking behavior of these MUAPs to determine their anatomical origin. EMG signals were recorded from the brachioradialis muscles of 5 normal subjects during moderate-level isometric contractions. MUAP waveforms, discharge patterns, and blocking were determined using computer-aided EMG decomposition. Twelve MUAPs with unstable satellite potentials were detected, always two together in the same signal. Each MUAP also had a second unstable component associated with its main spike. The blocking behavior of the unstable components depended on how close together the two MUAPs were when they discharged. The latencies and blocking behavior indicate that the unstable components came from branched muscle fibers innervated by two different motoneurons. The satellite potentials were due to action potentials that traveled to the branching point along one branch and back along the other. The blockings were due to action-potential collisions when both motoneurons discharged close together in time. Animal studies suggest that branched muscle fibers may be a normal characteristic of series-fibered muscles. This study adds to our understanding of these muscles in humans.

Origin and Properties of Striatal Local Field Potential Responses to Cortical Stimulation: Temporal Regulation by Fast Inhibitory Connections

PubMed Central

Galiñanes, Gregorio L.; Braz, Barbara Y.; Murer, Mario Gustavo

2011-01-01

Evoked striatal field potentials are seldom used to study corticostriatal communication in vivo because little is known about their origin and significance. Here we show that striatal field responses evoked by stimulating the prelimbic cortex in mice are reduced by more than 90% after infusing the AMPA receptor antagonist CNQX close to the recording electrode. Moreover, the amplitude of local field responses and dPSPs recorded in striatal medium spiny neurons increase in parallel with increasing stimulating current intensity. Finally, the evoked striatal fields show several of the basic known properties of corticostriatal transmission, including paired pulse facilitation and topographical organization. As a case study, we characterized the effect of local GABAA receptor blockade on striatal field and multiunitary action potential responses to prelimbic cortex stimulation. Striatal activity was recorded through a 24 channel silicon probe at about 600 µm from a microdialysis probe. Intrastriatal administration of the GABAA receptor antagonist bicuculline increased by 65±7% the duration of the evoked field responses. Moreover, the associated action potential responses were markedly enhanced during bicuculline infusion. Bicuculline enhancement took place at all the striatal sites that showed a response to cortical stimulation before drug infusion, but sites showing no field response before bicuculline remained unresponsive during GABAA receptor blockade. Thus, the data demonstrate that fast inhibitory connections exert a marked temporal regulation of input-output transformations within spatially delimited striatal networks responding to a cortical input. Overall, we propose that evoked striatal fields may be a useful tool to study corticostriatal synaptic connectivity in relation to behavior. PMID:22163020

Use of genetic algorithm for the selection of EEG features

NASA Astrophysics Data System (ADS)

Asvestas, P.; Korda, A.; Kostopoulos, S.; Karanasiou, I.; Ouzounoglou, A.; Sidiropoulos, K.; Ventouras, E.; Matsopoulos, G.

2015-09-01

Genetic Algorithm (GA) is a popular optimization technique that can detect the global optimum of a multivariable function containing several local optima. GA has been widely used in the field of biomedical informatics, especially in the context of designing decision support systems that classify biomedical signals or images into classes of interest. The aim of this paper is to present a methodology, based on GA, for the selection of the optimal subset of features that can be used for the efficient classification of Event Related Potentials (ERPs), which are recorded during the observation of correct or incorrect actions. In our experiment, ERP recordings were acquired from sixteen (16) healthy volunteers who observed correct or incorrect actions of other subjects. The brain electrical activity was recorded at 47 locations on the scalp. The GA was formulated as a combinatorial optimizer for the selection of the combination of electrodes that maximizes the performance of the Fuzzy C Means (FCM) classification algorithm. In particular, during the evolution of the GA, for each candidate combination of electrodes, the well-known (Σ, Φ, Ω) features were calculated and were evaluated by means of the FCM method. The proposed methodology provided a combination of 8 electrodes, with classification accuracy 93.8%. Thus, GA can be the basis for the selection of features that discriminate ERP recordings of observations of correct or incorrect actions.

Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

PubMed

Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

2014-03-05

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

Heteromeric Kv7.2/7.3 Channels Differentially Regulate Action Potential Initiation and Conduction in Neocortical Myelinated Axons

PubMed Central

Battefeld, Arne; Tran, Baouyen T.; Gavrilis, Jason; Cooper, Edward C.

2014-01-01

Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of Kv7 potassium channels and voltage-gated sodium (Nav) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these Kv7 channels and the functional impact of colocalization with Nav channels remain poorly understood. Here, we quantitatively examined Kv7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. Kv7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ∼12 (proximal) to 150 pS μm−2 (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by Kv7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (∼15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic Kv7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal Kv7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains Kv7.2/7.3 channels were found to increase Nav channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, Kv7 clustering near axonal Nav channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential. PMID:24599470

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

DOE PAGES

Qian, Fang; Huang, Chao; Lin, Yi-Dong; ...

2017-04-18

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Fang; Huang, Chao; Lin, Yi-Dong

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions andmore » under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.« less

Future of electronic health records: implications for decision support.

PubMed

Rothman, Brian; Leonard, Joan C; Vigoda, Michael M

2012-01-01

The potential benefits of the electronic health record over traditional paper are many, including cost containment, reductions in errors, and improved compliance by utilizing real-time data. The highest functional level of the electronic health record (EHR) is clinical decision support (CDS) and process automation, which are expected to enhance patient health and healthcare. The authors provide an overview of the progress in using patient data more efficiently and effectively through clinical decision support to improve health care delivery, how decision support impacts anesthesia practice, and how some are leading the way using these systems to solve need-specific issues. Clinical decision support uses passive or active decision support to modify clinician behavior through recommendations of specific actions. Recommendations may reduce medication errors, which would result in considerable savings by avoiding adverse drug events. In selected studies, clinical decision support has been shown to decrease the time to follow-up actions, and prediction has proved useful in forecasting patient outcomes, avoiding costs, and correctly prompting treatment plan modifications by clinicians before engaging in decision-making. Clinical documentation accuracy and completeness is improved by an electronic health record and greater relevance of care data is delivered. Clinical decision support may increase clinician adherence to clinical guidelines, but educational workshops may be equally effective. Unintentional consequences of clinical decision support, such as alert desensitization, can decrease the effectiveness of a system. Current anesthesia clinical decision support use includes antibiotic administration timing, improved documentation, more timely billing, and postoperative nausea and vomiting prophylaxis. Electronic health record implementation offers data-mining opportunities to improve operational, financial, and clinical processes. Using electronic health record data in real-time for decision support and process automation has the potential to both reduce costs and improve the quality of patient care. © 2012 Mount Sinai School of Medicine.

Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic Calcium Transients in the Frog Optic Tectum Layer 6 Neurons.

PubMed

Svirskis, Gytis; Baranauskas, Gytis; Svirskiene, Natasa; Tkatch, Tatiana

2015-01-01

The superior colliculus in mammals or the optic tectum in amphibians is a major visual information processing center responsible for generation of orientating responses such as saccades in monkeys or prey catching avoidance behavior in frogs. The conserved structure function of the superior colliculus the optic tectum across distant species such as frogs, birds monkeys permits to draw rather general conclusions after studying a single species. We chose the frog optic tectum because we are able to perform whole-cell voltage-clamp recordings fluorescence imaging of tectal neurons while they respond to a visual stimulus. In the optic tectum of amphibians most visual information is processed by pear-shaped neurons possessing long dendritic branches, which receive the majority of synapses originating from the retinal ganglion cells. Since the first step of the retinal input integration is performed on these dendrites, it is important to know whether this integration is enhanced by active dendritic properties. We demonstrate that rapid calcium transients coinciding with the visual stimulus evoked action potentials in the somatic recordings can be readily detected up to the fine branches of these dendrites. These transients were blocked by calcium channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via voltage-activated L-type calcium channels. The high speed of calcium transient propagation, >300 μm in <10 ms, is consistent with the notion that action potentials, actively propagating along dendrites, open voltage-gated L-type calcium channels causing rapid calcium concentration transients in the dendrites. We conclude that such activation by somatic action potentials of the dendritic voltage gated calcium channels in the close vicinity to the synapses formed by axons of the retinal ganglion cells may facilitate visual information processing in the principal neurons of the frog optic tectum.

Accuracy assessment of a surface electromyogram decomposition system in human first dorsal interosseus muscle

NASA Astrophysics Data System (ADS)

Hu, Xiaogang; Rymer, William Z.; Suresh, Nina L.

2014-04-01

Objective. The aim of this study is to assess the accuracy of a surface electromyogram (sEMG) motor unit (MU) decomposition algorithm during low levels of muscle contraction. Approach. A two-source method was used to verify the accuracy of the sEMG decomposition system, by utilizing simultaneous intramuscular and surface EMG recordings from the human first dorsal interosseous muscle recorded during isometric trapezoidal force contractions. Spike trains from each recording type were decomposed independently utilizing two different algorithms, EMGlab and dEMG decomposition algorithms. The degree of agreement of the decomposed spike timings was assessed for three different segments of the EMG signals, corresponding to specified regions in the force task. A regression analysis was performed to examine whether certain properties of the sEMG and force signal can predict the decomposition accuracy. Main results. The average accuracy of successful decomposition among the 119 MUs that were common to both intramuscular and surface records was approximately 95%, and the accuracy was comparable between the different segments of the sEMG signals (i.e., force ramp-up versus steady state force versus combined). The regression function between the accuracy and properties of sEMG and force signals revealed that the signal-to-noise ratio of the action potential and stability in the action potential records were significant predictors of the surface decomposition accuracy. Significance. The outcomes of our study confirm the accuracy of the sEMG decomposition algorithm during low muscle contraction levels and provide confidence in the overall validity of the surface dEMG decomposition algorithm.

The climate mitigation gap: education and government recommendations miss the most effective individual actions

NASA Astrophysics Data System (ADS)

Wynes, Seth; Nicholas, Kimberly A.

2017-07-01

Current anthropogenic climate change is the result of greenhouse gas accumulation in the atmosphere, which records the aggregation of billions of individual decisions. Here we consider a broad range of individual lifestyle choices and calculate their potential to reduce greenhouse gas emissions in developed countries, based on 148 scenarios from 39 sources. We recommend four widely applicable high-impact (i.e. low emissions) actions with the potential to contribute to systemic change and substantially reduce annual personal emissions: having one fewer child (an average for developed countries of 58.6 tonnes CO2-equivalent (tCO2e) emission reductions per year), living car-free (2.4 tCO2e saved per year), avoiding airplane travel (1.6 tCO2e saved per roundtrip transatlantic flight) and eating a plant-based diet (0.8 tCO2e saved per year). These actions have much greater potential to reduce emissions than commonly promoted strategies like comprehensive recycling (four times less effective than a plant-based diet) or changing household lightbulbs (eight times less). Though adolescents poised to establish lifelong patterns are an important target group for promoting high-impact actions, we find that ten high school science textbooks from Canada largely fail to mention these actions (they account for 4% of their recommended actions), instead focusing on incremental changes with much smaller potential emissions reductions. Government resources on climate change from the EU, USA, Canada, and Australia also focus recommendations on lower-impact actions. We conclude that there are opportunities to improve existing educational and communication structures to promote the most effective emission-reduction strategies and close this mitigation gap.

Optophysiological Approach to Resolve Neuronal Action Potentials with High Spatial and Temporal Resolution in Cultured Neurons

PubMed Central

Pagès, Stéphane; Côté, Daniel; De Koninck, Paul

2011-01-01

Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm). Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs) have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser-scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (>10% of fluorescence change for 100 mV depolarization) and time response (sub millisecond) of the dye allows the robust detection of action potentials (APs) even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive, and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms) resolution and high spatial (μm) resolution. PMID:22016723

25 CFR 62.10 - Action by the Director.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Secretary for final action together with any relevant information or records; the recommendations of the... to the Assistant Secretary for final action together with any relevant information or records; the... record as presented together with such additional information as may be considered pertinent. Any...

Simulation study on compressive laminar optical tomography for cardiac action potential propagation

PubMed Central

Harada, Takumi; Tomii, Naoki; Manago, Shota; Kobayashi, Etsuko; Sakuma, Ichiro

2017-01-01

To measure the activity of tissue at the microscopic level, laminar optical tomography (LOT), which is a microscopic form of diffuse optical tomography, has been developed. However, obtaining sufficient recording speed to determine rapidly changing dynamic activity remains major challenges. For a high frame rate of the reconstructed data, we here propose a new LOT method using compressed sensing theory, called compressive laminar optical tomography (CLOT), in which novel digital micromirror device-based illumination and data reduction in a single reconstruction are applied. In the simulation experiments, the reconstructed volumetric images of the action potentials that were acquired from 5 measured images with random pattern featured a wave border at least to a depth of 2.5 mm. Consequently, it was shown that CLOT has potential for over 200 fps required for the cardiac electrophysiological phenomena. PMID:28736675

Reactive oxygen species alters the electrophysiological properties and raises [Ca2+]i in intracardiac ganglion neurons

PubMed Central

Dyavanapalli, Jhansi; Rimmer, Katrina

2010-01-01

We have investigated the effects of the reactive oxygen species (ROS) donors hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) on the intrinsic electrophysiological characteristics: ganglionic transmission and resting [Ca2+]i in neonate and adult rat intracardiac ganglion (ICG) neurons. Intracellular recordings were made using sharp microelectrodes filled with either 0.5 M KCl or Oregon Green 488 BAPTA-1, allowing recording of electrical properties and measurement of [Ca2+]i. H2O2 and t-BHP both hyperpolarized the resting membrane potential and reduced membrane resistance. In adult ICG neurons, the hyperpolarizing action of H2O2 was reversed fully by Ba2+ and partially by tetraethylammonium, muscarine, and linopirdine. H2O2 and t-BHP reduced the action potential afterhyperpolarization (AHP) amplitude but had no impact on either overshoot or AHP duration. ROS donors evoked an increase in discharge adaptation to long depolarizing current pulses. H2O2 blocked ganglionic transmission in most ICG neurons but did not alter nicotine-evoked depolarizations. By contrast, t-BHP had no significant action on ganglionic transmission. H2O2 and t-BHP increased resting intracellular Ca2+ levels to 1.6 ( ± 0.6, n = 11, P < 0.01) and 1.6 ( ± 0.3, n = 8, P < 0.001), respectively, of control value (1.0, ∼60 nM). The ROS scavenger catalase prevented the actions of H2O2, and this protection extended beyond the period of application. Superoxide dismutase partially shielded against the action of H2O2, but this was limited to the period of application. These data demonstrate that ROS decreases the excitability and ganglionic transmission of ICG neurons, attenuating parasympathetic control of the heart. PMID:20445155

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

PubMed Central

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-01-01

Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

PubMed

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-03-01

To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

Predictive monitoring of actions, EEG recordings in virtual reality.

PubMed

Ozkan, Duru G; Pezzetta, Rachele

2018-04-01

Error-related negativity (ERN) is a signal that is associated with error detection. Joch and colleagues (Joch M, Hegele M, Maurer H, Müller H, Maurer LK. J Neurophysiol 118: 486-495, 2017) successfully separated the ERN as a response to online prediction error from feedback updates. We discuss the role of ERN in action and suggest insights from virtual reality techniques; we consider the potential benefit of self-evaluation in determining the mechanisms of ERN amplitude; finally, we review the oscillatory activity that has been claimed to accompany ERN.

Using Electrically-evoked Compound Action Potentials to Estimate Perceptive Levels in Experienced Adult Cochlear Implant Users.

PubMed

Joly, Charles-Alexandre; Péan, Vincent; Hermann, Ruben; Seldran, Fabien; Thai-Van, Hung; Truy, Eric

2017-10-01

The cochlear implant (CI) fitting level prediction accuracy of electrically-evoked compound action potential (ECAP) should be enhanced by the addition of demographic data in models. No accurate automated fitting of CI based on ECAP has yet been proposed. We recorded ECAP in 45 adults who had been using MED-EL CIs for more than 11 months and collected the most comfortable loudness level (MCL) used for CI fitting (prog-MCL), perception thresholds (meas-THR), and MCL (meas-MCL) measured with the stimulation used for ECAP recording. Linear mixed models taking into account cochlear site factors were computed to explain prog-MCL, meas-MCL, and meas-THR. Cochlear region and ECAP threshold were predictors of the three levels. In addition, significant predictors were the ECAP amplitude for the prog-MCL and the duration of deafness for the prog-MCL and the meas-THR. Estimations were more accurate for the meas-THR, then the meas-MCL, and finally the prog-MCL. These results show that 1) ECAP thresholds are more closely related to perception threshold than to comfort level, 2) predictions are more accurate when the inter-subject and cochlear regions variations are considered, and 3) differences between the stimulations used for ECAP recording and for CI fitting make it difficult to accurately predict the prog-MCL from the ECAP recording. Predicted prog-MCL could be used as bases for fitting but should be used with care to avoid any uncomfortable or painful stimulation.

Excitability is increased in hippocampal CA1 pyramidal cells of Fmr1 knockout mice

PubMed Central

Luque, M. Angeles; Beltran-Matas, Pablo; Marin, M. Carmen; Torres, Blas

2017-01-01

Fragile X syndrome (FXS) is caused by a failure of neuronal cells to express the gene encoding the fragile mental retardation protein (FMRP). Clinical features of the syndrome include intellectual disability, learning impairment, hyperactivity, seizures and anxiety. Fmr1 knockout (KO) mice do not express FMRP and, as a result, reproduce some FXS behavioral abnormalities. While intrinsic and synaptic properties of excitatory cells in various part of the brain have been studied in Fmr1 KO mice, a thorough analysis of action potential characteristics and input-output function of CA1 pyramidal cells in this model is lacking. With a view to determining the effects of the absence of FMRP on cell excitability, we studied rheobase, action potential duration, firing frequency–current intensity relationship and action potential after-hyperpolarization (AHP) in CA1 pyramidal cells of the hippocampus of wild type (WT) and Fmr1 KO male mice. Brain slices were prepared from 8- to 12-week-old mice and the electrophysiological properties of cells recorded. Cells from both groups had similar resting membrane potentials. In the absence of FMRP expression, cells had a significantly higher input resistance, while voltage threshold and depolarization voltage were similar in WT and Fmr1 KO cell groups. No changes were observed in rheobase. The action potential duration was longer in the Fmr1 KO cell group, and the action potential firing frequency evoked by current steps of the same intensity was higher. Moreover, the gain (slope) of the relationship between firing frequency and injected current was 1.25-fold higher in the Fmr1 KO cell group. Finally, AHP amplitude was significantly reduced in the Fmr1 KO cell group. According to these data, FMRP absence increases excitability in hippocampal CA1 pyramidal cells. PMID:28931075

Towards a magnetoresistive platform for neural signal recording

NASA Astrophysics Data System (ADS)

Sharma, P. P.; Gervasoni, G.; Albisetti, E.; D'Ercoli, F.; Monticelli, M.; Moretti, D.; Forte, N.; Rocchi, A.; Ferrari, G.; Baldelli, P.; Sampietro, M.; Benfenati, F.; Bertacco, R.; Petti, D.

2017-05-01

A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

47 CFR 0.285 - Record of actions taken.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMISSION ORGANIZATION Delegations of Authority Chief, Media Bureau § 0.285 Record of actions taken. The history card, the station file, and other appropriate files are designated to be the official records of action taken by the Chief of the Media Bureau. The...

Neurotransmitter Release Can Be Stabilized by a Mechanism That Prevents Voltage Changes Near the End of Action Potentials from Affecting Calcium Currents

PubMed Central

Clarke, Stephen G.; Scarnati, Matthew S.

2016-01-01

At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating. In support of this, presynaptic calcium entry is affected by afterpotentials after standard instant voltage jumps. Here, we used the mouse calyx of Held synapse, which allows simultaneous presynaptic and postsynaptic patch-clamp recording, to show that the postsynaptic response is affected significantly by presynaptic afterpotentials after voltage jumps. We therefore tested the effects of presynaptic afterpotentials using simultaneous presynaptic and postsynaptic recordings and AP waveforms or real APs. Surprisingly, presynaptic afterpotentials after AP stimuli did not alter calcium channel responses or neurotransmitter release appreciably. We show that the AP repolarization time course causes afterpotential-induced changes in calcium driving force and changes in calcium channel gating to effectively cancel each other out. This mechanism, in which electrical driving force is balanced by channel gating, prevents changes in calcium influx from occurring at the end of the AP and therefore acts to stabilize synaptic transmission. In addition, this mechanism can act to stabilize neurotransmitter release when the presynaptic resting potential changes. SIGNIFICANCE STATEMENT The shape of presynaptic action potentials (APs), particularly the falling phase, affects calcium entry and small changes in calcium influx can produce large changes in postsynaptic responses. We hypothesized that afterpotentials, which often follow APs, affect calcium entry and neurotransmitter release. We tested this in calyx of Held nerve terminals, which allow simultaneous recording of presynaptic calcium currents and postsynaptic responses. Surprisingly, presynaptic afterpotentials did not alter calcium current or neurotransmitter release. We show that the AP falling phase causes afterpotential-induced changes in electrical driving force and calcium channel gating to cancel each other out. This mechanism regulates calcium entry at the end of APs and therefore stabilizes synaptic transmission. This also stabilizes responses when the presynaptic resting potential changes. PMID:27911759

Neurotransmitter Release Can Be Stabilized by a Mechanism That Prevents Voltage Changes Near the End of Action Potentials from Affecting Calcium Currents.

PubMed

Clarke, Stephen G; Scarnati, Matthew S; Paradiso, Kenneth G

2016-11-09

At chemical synapses, presynaptic action potentials (APs) activate voltage-gated calcium channels, allowing calcium to enter and trigger neurotransmitter release. The duration, peak amplitude, and shape of the AP falling phase alter calcium entry, which can affect neurotransmitter release significantly. In many neurons, APs do not immediately return to the resting potential, but instead exhibit a period of depolarization or hyperpolarization referred to as an afterpotential. We hypothesized that presynaptic afterpotentials should alter neurotransmitter release by affecting the electrical driving force for calcium entry and calcium channel gating. In support of this, presynaptic calcium entry is affected by afterpotentials after standard instant voltage jumps. Here, we used the mouse calyx of Held synapse, which allows simultaneous presynaptic and postsynaptic patch-clamp recording, to show that the postsynaptic response is affected significantly by presynaptic afterpotentials after voltage jumps. We therefore tested the effects of presynaptic afterpotentials using simultaneous presynaptic and postsynaptic recordings and AP waveforms or real APs. Surprisingly, presynaptic afterpotentials after AP stimuli did not alter calcium channel responses or neurotransmitter release appreciably. We show that the AP repolarization time course causes afterpotential-induced changes in calcium driving force and changes in calcium channel gating to effectively cancel each other out. This mechanism, in which electrical driving force is balanced by channel gating, prevents changes in calcium influx from occurring at the end of the AP and therefore acts to stabilize synaptic transmission. In addition, this mechanism can act to stabilize neurotransmitter release when the presynaptic resting potential changes. The shape of presynaptic action potentials (APs), particularly the falling phase, affects calcium entry and small changes in calcium influx can produce large changes in postsynaptic responses. We hypothesized that afterpotentials, which often follow APs, affect calcium entry and neurotransmitter release. We tested this in calyx of Held nerve terminals, which allow simultaneous recording of presynaptic calcium currents and postsynaptic responses. Surprisingly, presynaptic afterpotentials did not alter calcium current or neurotransmitter release. We show that the AP falling phase causes afterpotential-induced changes in electrical driving force and calcium channel gating to cancel each other out. This mechanism regulates calcium entry at the end of APs and therefore stabilizes synaptic transmission. This also stabilizes responses when the presynaptic resting potential changes. Copyright © 2016 the authors 0270-6474/16/3611559-14$15.00/0.

Flexible microelectrode array for interfacing with the surface of neural ganglia

NASA Astrophysics Data System (ADS)

Sperry, Zachariah J.; Na, Kyounghwan; Parizi, Saman S.; Chiel, Hillel J.; Seymour, John; Yoon, Euisik; Bruns, Tim M.

2018-06-01

Objective. The dorsal root ganglia (DRG) are promising nerve structures for sensory neural interfaces because they provide centralized access to primary afferent cell bodies and spinal reflex circuitry. In order to harness this potential, new electrode technologies are needed which take advantage of the unique properties of DRG, specifically the high density of neural cell bodies at the dorsal surface. Here we report initial in vivo results from the development of a flexible non-penetrating polyimide electrode array interfacing with the surface of ganglia. Approach. Multiple layouts of a 64-channel iridium electrode (420 µm2) array were tested, with pitch as small as 25 µm. The buccal ganglia of invertebrate sea slug Aplysia californica were used to develop handling and recording techniques with ganglionic surface electrode arrays (GSEAs). We also demonstrated the GSEA’s capability to record single- and multi-unit activity from feline lumbosacral DRG related to a variety of sensory inputs, including cutaneous brushing, joint flexion, and bladder pressure. Main results. We recorded action potentials from a variety of Aplysia neurons activated by nerve stimulation, and units were observed firing simultaneously on closely spaced electrode sites. We also recorded single- and multi-unit activity associated with sensory inputs from feline DRG. We utilized spatial oversampling of action potentials on closely-spaced electrode sites to estimate the location of neural sources at between 25 µm and 107 µm below the DRG surface. We also used the high spatial sampling to demonstrate a possible spatial sensory map of one feline’s DRG. We obtained activation of sensory fibers with low-amplitude stimulation through individual or groups of GSEA electrode sites. Significance. Overall, the GSEA has been shown to provide a variety of information types from ganglia neurons and to have significant potential as a tool for neural mapping and interfacing.

Voltage-dependent dynamic FRET signals from the transverse tubules in mammalian skeletal muscle fibers.

PubMed

DiFranco, Marino; Capote, Joana; Quiñonez, Marbella; Vergara, Julio L

2007-12-01

Two hybrid voltage-sensing systems based on fluorescence resonance energy transfer (FRET) were used to record membrane potential changes in the transverse tubular system (TTS) and surface membranes of adult mice skeletal muscle fibers. Farnesylated EGFP or ECFP (EGFP-F and ECFP-F) were used as immobile FRET donors, and either non-fluorescent (dipicrylamine [DPA]) or fluorescent (oxonol dye DiBAC(4)(5)) lipophilic anions were used as mobile energy acceptors. Flexor digitorum brevis (FDB) muscles were transfected by in vivo electroporation with pEGFP-F and pECFP-F. Farnesylated fluorescent proteins were efficiently expressed in the TTS and surface membranes. Voltage-dependent optical signals resulting from resonance energy transfer from fluorescent proteins to DPA were named QRET transients, to distinguish them from FRET transients recorded using DiBAC(4)(5). The peak DeltaF/F of QRET transients elicited by action potential stimulation is twice larger in fibers expressing ECFP-F as those with EGFP-F (7.1% vs. 3.6%). These data provide a unique experimental demonstration of the importance of the spectral overlap in FRET. The voltage sensitivity of QRET and FRET signals was demonstrated to correspond to the voltage-dependent translocation of the charged acceptors, which manifest as nonlinear components in current records. For DPA, both electrical and QRET data were predicted by radial cable model simulations in which the maximal time constant of charge translocation was 0.6 ms. FRET signals recorded in response to action potentials in fibers stained with DiBAC(4)(5) exhibit DeltaF/F amplitudes as large as 28%, but their rising phase was slower than those of QRET signals. Model simulations require a time constant for charge translocation of 1.6 ms in order to predict current and FRET data. Our results provide the basis for the potential use of lipophilic ions as tools to test for fast voltage-dependent conformational changes of membrane proteins in the TTS.

A simultaneous multichannel monophasic action potential electrode array for in vivo epicardial repolarization mapping.

PubMed

Sahakian, A V; Peterson, M S; Shkurovich, S; Hamer, M; Votapka, T; Ji, T; Swiryn, S

2001-03-01

While the recording of extracellular monophasic action potentials (MAPs) from single epicardial or endocardial sites has been performed for over a century, we are unaware of any previous successful attempt to record MAPs simultaneously from a large number of sites in vivo. We report here the design and validation of an array of MAP electrodes which records both depolarization and repolarization simultaneously at up to 16 epicardial sites in a square array on the heart in vivo. The array consists of 16 sintered Ag-AgCl electrodes mounted in a common housing with individual suspensions allowing each electrode to exert a controlled pressure on the epicardial surface. The electrodes are arranged in a square array, with each quadrant of four having an additional recessed sintered Ag-AgCl reference electrode at its center. A saline-soaked sponge establishes ionic contact between the reference electrodes and the tissue. The array was tested on six anesthetized open-chested pigs. Simultaneous diagnostic-quality MAP recordings were obtained from up to 13 out of 16 ventricular sites. Ventricular MAPs had amplitudes of 10-40 mV with uniform morphologies and stable baselines for up to 30 min. MAP duration at 90% repolarization was measured and shown to vary as expected with cycle length during sustained pacing. The relationship between MAP duration and effective refractory period was also confirmed. The ability of the array to detect local differences in repolarization was tested in two ways. Placement of the array straddling the atrioventricular (AV) junction yielded simultaneous atrial or ventricular recordings at corresponding sites during 1:1 and 2:1 AV conduction. Localized ischemia via constriction of a coronary artery branch resulted in shortening of the repolarization phase at the ischemic, but not the nonischemic, sites. In conclusion, these results indicate that the simultaneous multichannel MAP electrode array is a viable method for in vivo epicardial repolarization mapping. The array has the potential to be expanded to increase the number of sites and spatial resolution.

Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex

PubMed Central

Major, Sebastian; Pannek, Heinz-Wolfgang; Woitzik, Johannes; Scheel, Michael; Wiesenthal, Dirk; Martus, Peter; Winkler, Maren K.L.; Hartings, Jed A.; Fabricius, Martin; Speckmann, Erwin-Josef; Gorji, Ali

2012-01-01

Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating channels initiates spreading depression of brain activity. In contrast, epileptic seizures show modest ion translocation and sustained depolarization below the inactivation threshold for action potential generating channels. Such modest sustained depolarization allows synchronous, highly frequent neuronal firing; ictal epileptic field potentials being its electrocorticographic and epileptic seizure its clinical correlate. Nevertheless, Leão in 1944 and Van Harreveld and Stamm in 1953 described in animals that silencing of brain activity induced by spreading depolarization changed during minimal electrical stimulations. Eventually, epileptic field potentials were recorded during the period that had originally seen spreading depression of activity. Such spreading convulsions are characterized by epileptic field potentials on the final shoulder of the large slow potential change of spreading depolarization. We here report on such spreading convulsions in monopolar subdural recordings in 2 of 25 consecutive aneurismal subarachnoid haemorrhage patients in vivo and neocortical slices from 12 patients with intractable temporal lobe epilepsy in vitro. The in vitro results suggest that γ-aminobutyric acid-mediated inhibition protects from spreading convulsions. Moreover, we describe arterial pulse artefacts mimicking epileptic field potentials in three patients with subarachnoid haemorrhage that ride on the slow potential peak. Twenty-one of the 25 subarachnoid haemorrhage patients (84%) had 656 spreading depolarizations in contrast to only three patients (12%) with 55 ictal epileptic events isolated from spreading depolarizations. Spreading depolarization frequency and depression periods per 24 h recording episodes showed an early and a delayed peak on Day 7. Patients surviving subarachnoid haemorrhage with poor outcome at 6 months showed significantly higher total and peak numbers of spreading depolarizations and significantly longer total and peak depression periods during the electrocorticographic monitoring than patients with good outcome. In a semi-structured telephone interview 3 years after the initial haemorrhage, 44% of the subarachnoid haemorrhage survivors had developed late post-haemorrhagic seizures requiring anti-convulsant medication. In those patients, peak spreading depolarization number had been significantly higher [15.1 (11.4–30.8) versus 7.0 (0.8–11.2) events per day, P = 0.045]. In summary, monopolar recordings here provided unequivocal evidence of spreading convulsions in patients. Hence, practically all major pathological cortical network events in animals have now been observed in people. Early spreading depolarizations may indicate a risk for late post-haemorrhagic seizures. PMID:22120143

Comparison of the protective effects of ferulic acid and its drug-containing plasma on primary cultured neonatal rat cardiomyocytes with hypoxia/reoxygenation injury

PubMed Central

Ren, Cong; Bao, Yong-rui; Meng, Xian-sheng; Diao, Yun-peng; Kang, Ting-guo

2013-01-01

Backgroud: To simulate the ischemia-reperfusion injury in vivo, hypoxia/reoxygenation injury model was established in vitro and primary cultured neonatal rat cardiomyocytes were underwent hypoxia with hydrosulfite (Na2S2O4) for 1 h followed by 1 h reoxygenation. Materials and Methods: Determination the cell viability by MTT colorimetric assay. We use kit to detect the activity of lactate dehydrogenase (LDH), Na+-K+-ATPase and Ca2+-ATPase. Do research on the effect which ferulic acid and its drug-containing plasma have to self-discipline, conductivity, action potential duration and other electrophysiological phenomena of myocardial cells by direct observation using a microscope and recording method of intracellular action potential. Results: The experimental datum showed that both can reduce the damage hydrosulfite to myocardial cell damage and improve myocardial viability, reduce the amount of LDH leak, increase activity of Na+-K+-ATPase, Ca2+-ATPase, and increase APA (Action potential amplitude), Vmax (Maximum rate of depolarization) and MPD (Maximum potential diastolic). Conclusion: Taken together, therefore, we can get the conclusion that ferulic acid drug-containing plasma has better protective effect injured myocardial cell than ferulic acid. PMID:23930002

Action prediction based on anticipatory brain potentials during simulated driving

NASA Astrophysics Data System (ADS)

Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

2015-12-01

Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

Trial-Type Dependent Frames of Reference for Value Comparison

PubMed Central

Hunt, Laurence T.; Woolrich, Mark W.; Rushworth, Matthew F. S.; Behrens, Timothy E. J.

2013-01-01

A central question in cognitive neuroscience regards the means by which options are compared and decisions are resolved during value-guided choice. It is clear that several component processes are needed; these include identifying options, a value-based comparison, and implementation of actions to execute the decision. What is less clear is the temporal precedence and functional organisation of these component processes in the brain. Competing models of decision making have proposed that value comparison may occur in the space of alternative actions, or in the space of abstract goods. We hypothesized that the signals observed might in fact depend upon the framing of the decision. We recorded magnetoencephalographic data from humans performing value-guided choices in which two closely related trial types were interleaved. In the first trial type, each option was revealed separately, potentially causing subjects to estimate each action's value as it was revealed and perform comparison in action-space. In the second trial type, both options were presented simultaneously, potentially leading to comparison in abstract goods-space prior to commitment to a specific action. Distinct activity patterns (in distinct brain regions) on the two trial types demonstrated that the observed frame of reference used for decision making indeed differed, despite the information presented being formally identical, between the two trial types. This provides a potential reconciliation of conflicting accounts of value-guided choice. PMID:24068906

43 CFR 2.61 - Requests for notification of existence of records: Action on.

Code of Federal Regulations, 2010 CFR

2010-10-01

... contains records pertaining to them unless (i) the records were compiled in reasonable anticipation of a... reasonable anticipation of a civil action or proceeding or the system of records is one which has been...

40 CFR 63.9550 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c..., maintenance, corrective action, report, or record, according to § 63.10(b)(1). You can keep the records...

40 CFR 63.7192 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c..., maintenance, corrective action, report, or record, according to § 63.10(b)(1). You can keep the records...

40 CFR 63.8822 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c..., maintenance, corrective action, report, or record, according to § 63.10(b)(1). You can keep the records...

High-Impact Actions for Individuals to Reduce Greenhouse Gas Emissions

NASA Astrophysics Data System (ADS)

Nicholas, K. A.; Wynes, S. C.

2015-12-01

Climate change is the result of greenhouse gas accumulation in the atmosphere, which records the aggregation of billions of individual decisions. While systemic and structural changes receive great attention for addressing climate change, the contribution that individual citizens can make is often overlooked, especially in developed countries where per-capita emissions are highest. Here we consider a broad range of individual lifestyle choices and calculate their potential to reduce greenhouse gas emissions. We find that four widely applicable high-impact actions have the potential to reduce personal emissions by more than 1 tonne CO2-equivalent per year: having one fewer child (59.2 tonnes of reductions), living car-free (2.3 tonnes), avoiding airplane travel (1.5 tonnes per flight) and eating a plant-based diet (0.82 tonnes). These actions have much greater potential to reduce emissions than commonly promoted strategies like recycling (4 times less effective than a plant-based diet) or changing lightbulbs (8 times). However, high school textbooks from Canada and government resources from the EU, USA, Canada, and Australia largely fail to mention these actions, instead focusing on incremental changes with much smaller potential impact. We conclude that climate policy should focus not only on national and international targets, but also on encouraging responsible behaviour, especially for adolescents who will grow up in the era of climate change and are poised to establish a lifelong pattern of sustainable lifestyle choices.

T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure.

PubMed

Crocini, Claudia; Coppini, Raffaele; Ferrantini, Cecilia; Yan, Ping; Loew, Leslie M; Poggesi, Corrado; Cerbai, Elisabetta; Pavone, Francesco S; Sacconi, Leonardo

2016-09-03

Alterations of the β-adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of β-adrenoceptor activation on local Ca(2+) release in electrically coupled and uncoupled T-tubules in ventricular myocytes from HF rats. We employ an ultrafast random access multi-photon (RAMP) microscope to simultaneously record action potentials and Ca(2+) transients from multiple T-tubules in ventricular cardiomyocytes from a HF rat model of coronary ligation compared to sham-operated rats as a control. We confirmed that β-adrenergic stimulation increases the frequency of Ca(2+) sparks, reduces Ca(2+) transient variability, and hastens the decay of Ca(2+) transients: all these effects are similarly exerted by β-adrenergic stimulation in control and HF cardiomyocytes. Conversely, β-adrenergic stimulation in HF cells accelerates a Ca(2+) rise exclusively in the proximity of T-tubules that regularly conduct the action potential. The delayed Ca(2+) rise found at T-tubules that fail to conduct the action potential is instead not affected by β-adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to β-adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the β-adrenergic signalling may be directly caused by the lack of electrical activity.

29 CFR 1209.06 - Action necessary to close meetings; record of votes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Action necessary to close meetings; record of votes. 1209.06 Section 1209.06 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD PUBLIC OBSERVATION OF NATIONAL MEDIATION BOARD MEETINGS § 1209.06 Action necessary to close meetings; record of votes...

40 CFR 300.820 - Administrative record file for a removal action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SUBSTANCES POLLUTION CONTINGENCY PLAN Administrative Record for Selection of Response Action § 300.820 Administrative record file for a removal action. (a) If, based on the site evaluation, the lead agency determines... public comment. At such time, the lead agency shall publish in a major local newspaper of general...

40 CFR 300.800 - Establishment of an administrative record.

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLLUTION CONTINGENCY PLAN Administrative Record for Selection of Response Action § 300.800 Establishment of... agency for a federal facility. (3) If EPA is involved in the selection of the response action at a... record that contains the documents that form the basis for the selection of a response action. The lead...

40 CFR 300.800 - Establishment of an administrative record.

Code of Federal Regulations, 2010 CFR

2010-07-01

... POLLUTION CONTINGENCY PLAN Administrative Record for Selection of Response Action § 300.800 Establishment of... agency for a federal facility. (3) If EPA is involved in the selection of the response action at a... record that contains the documents that form the basis for the selection of a response action. The lead...

40 CFR 300.800 - Establishment of an administrative record.

Code of Federal Regulations, 2014 CFR

2014-07-01

... POLLUTION CONTINGENCY PLAN Administrative Record for Selection of Response Action § 300.800 Establishment of... agency for a federal facility. (3) If EPA is involved in the selection of the response action at a... record that contains the documents that form the basis for the selection of a response action. The lead...

40 CFR 300.800 - Establishment of an administrative record.

Code of Federal Regulations, 2012 CFR

2012-07-01

... POLLUTION CONTINGENCY PLAN Administrative Record for Selection of Response Action § 300.800 Establishment of... agency for a federal facility. (3) If EPA is involved in the selection of the response action at a... record that contains the documents that form the basis for the selection of a response action. The lead...

40 CFR 300.800 - Establishment of an administrative record.

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTION CONTINGENCY PLAN Administrative Record for Selection of Response Action § 300.800 Establishment of... agency for a federal facility. (3) If EPA is involved in the selection of the response action at a... record that contains the documents that form the basis for the selection of a response action. The lead...

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

PubMed Central

Debanne, D; Guérineau, N C; Gähwiler, B H; Thompson, S M

1996-01-01

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles. PMID:9011608

Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

PubMed Central

Vivekananda, Umesh; Novak, Pavel; Bello, Oscar D.; Korchev, Yuri E.; Krishnakumar, Shyam S.; Volynski, Kirill E.; Kullmann, Dimitri M.

2017-01-01

Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog–digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels. PMID:28193892

Automated patch clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction.

PubMed

Stoelzle, Sonja; Haythornthwaite, Alison; Kettenhofen, Ralf; Kolossov, Eugen; Bohlen, Heribert; George, Michael; Brüggemann, Andrea; Fertig, Niels

2011-09-01

Cardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. Similar to primary cells, in vitro-generated stem cell-derived cardiomyocytes simultaneously express cardiac ion channels. Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. The aim of this study was to determine if stem cell-derived cardiomyocytes are suited for use in an automated patch clamp system. The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell-derived cardiomyocytes. Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system.

Nonlinear Dynamic Modeling of Neuron Action Potential Threshold During Synaptically Driven Broadband Intracellular Activity

PubMed Central

Roach, Shane M.; Song, Dong; Berger, Theodore W.

2012-01-01

Activity-dependent variation of neuronal thresholds for action potential (AP) generation is one of the key determinants of spike-train temporal-pattern transformations from presynaptic to postsynaptic spike trains. In this study, we model the nonlinear dynamics of the threshold variation during synaptically driven broadband intracellular activity. First, membrane potentials of single CA1 pyramidal cells were recorded under physiologically plausible broadband stimulation conditions. Second, a method was developed to measure AP thresholds from the continuous recordings of membrane potentials. It involves measuring the turning points of APs by analyzing the third-order derivatives of the membrane potentials. Four stimulation paradigms with different temporal patterns were applied to validate this method by comparing the measured AP turning points and the actual AP thresholds estimated with varying stimulation intensities. Results show that the AP turning points provide consistent measurement of the AP thresholds, except for a constant offset. It indicates that 1) the variation of AP turning points represents the nonlinearities of threshold dynamics; and 2) an optimization of the constant offset is required to achieve accurate spike prediction. Third, a nonlinear dynamical third-order Volterra model was built to describe the relations between the threshold dynamics and the AP activities. Results show that the model can predict threshold accurately based on the preceding APs. Finally, the dynamic threshold model was integrated into a previously developed single neuron model and resulted in a 33% improvement in spike prediction. PMID:22156947

Toward on-chip, in-cell recordings from cultured cardiomyocytes by arrays of gold mushroom-shaped microelectrodes

PubMed Central

Fendyur, Anna; Spira, Micha E.

2012-01-01

Cardiological research greatly rely on the use of cultured primary cardiomyocytes (CMs). The prime methodology to assess CM network electrophysiology is based on the use of extracellular recordings by substrate-integrated planar Micro-Electrode Arrays (MEAs). Whereas this methodology permits simultaneous, long-term monitoring of the CM electrical activity, it limits the information to extracellular field potentials (FPs). The alternative method of intracellular action potentials (APs) recordings by sharp- or patch-microelectrodes is limited to a single cell at a time. Here, we began to merge the advantages of planar MEA and intracellular microelectrodes. To that end we cultured rat CM on micrometer size protruding gold mushroom-shaped microelectrode (gMμEs) arrays. Cultured CMs engulf the gMμE permitting FPs recordings from individual cells. Local electroporation of a CM converts the extracellular recording configuration to attenuated intracellular APs with shape and duration similar to those recorded intracellularly. The procedure enables to simultaneously record APs from an unlimited number of CMs. The electroporated membrane spontaneously recovers. This allows for repeated recordings from the same CM a number of times (>8) for over 10 days. The further development of CM-gMμE configuration opens up new venues for basic and applied biomedical research. PMID:22936913

40 CFR 63.3931 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c..., maintenance, corrective action, report, or record according to § 63.10(b)(1). You may keep the records off...

40 CFR 63.8645 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c) You..., maintenance, corrective action, report, or record, according to § 63.10(b)(1). You may keep the records...

40 CFR 63.4313 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c..., maintenance, corrective action, report, or record, according to § 63.10(b)(1). You may keep the records off...

40 CFR 63.7843 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c..., maintenance, corrective action, report, or record according to § 63.10(b)(1). You can keep the records offsite...

Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi

Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compoundmore » action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.« less

Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle

PubMed Central

Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L

1999-01-01

We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014

The afterhyperpolarizing potential following a train of action potentials is suppressed in an acute epilepsy model in the rat Cornu Ammonis 1 area.

PubMed

Kernig, K; Kirschstein, T; Würdemann, T; Rohde, M; Köhling, R

2012-01-10

In hippocampal Cornu Ammonis 1 (CA1) neurons, a prolonged depolarization evokes a train of action potentials followed by a prominent afterhyperpolarizing potential (AHP), which critically dampens neuronal excitability. Because it is not known whether epileptiform activity alters the AHP and whether any alteration of the AHP is independent of inhibition, we acutely induced epileptiform activity by bath application of the GABA(A) receptor blocker gabazine (5 μM) in the rat hippocampal slice preparation and studied its impact on the AHP using intracellular recordings. Following 10 min of gabazine wash-in, slices started to develop spontaneous epileptiform discharges. This disinhibition was accompanied by a significant shift of the resting membrane potential of CA1 neurons to more depolarized values. Prolonged depolarizations (600 ms) elicited a train of action potentials, the number of which was not different between baseline and gabazine treatment. However, the AHP following the train of action potentials was significantly reduced after 20 min of gabazine treatment. When the induction of epileptiform activity was prevented by co-application of 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX, 10 μM) and D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 μM) to block α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors, respectively, the AHP was preserved despite of GABA(A) receptor inhibition suggesting that the epileptiform activity was required to suppress the AHP. Moreover, the AHP was also preserved when the slices were treated with the protein kinase blockers H-9 (100 μM) and H-89 (1 μM). These results demonstrate that the AHP following a train of action potentials is rapidly suppressed by acutely induced epileptiform activity due to a phosphorylation process-presumably involving protein kinase A. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

[Site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials and refractory using the Nucleus 24 standard].

PubMed

Ma, R Y; Li, W; Jiang, X J

2016-12-01

Objective: To investigate the correlation between the site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials. Method: Recordings of auditory nerve responses were conducted in 32 prelingual subjects to demonstrate the feasibility of ECAP recordings using the nerve response telemetry(NRT) feature of the Nucleus CI24R(CA) system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Result: Findings of our prelingual children showed significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function hadbeen observed. The refractory time showed an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusion: Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences between prelingual children and adults could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

The ionic bases of the action potential in isolated mouse cardiac Purkinje cell.

PubMed

Vaidyanathan, Ravi; O'Connell, Ryan P; Deo, Makarand; Milstein, Michelle L; Furspan, Philip; Herron, Todd J; Pandit, Sandeep V; Musa, Hassan; Berenfeld, Omer; Jalife, José; Anumonwo, Justus M B

2013-01-01

Collecting electrophysiological and molecular data from the murine conduction system presents technical challenges. Thus, only little advantage has been taken of numerous genetically engineered murine models to study excitation through the cardiac conduction system of the mouse. To develop an approach for isolating murine cardiac Purkinje cells (PCs), to characterize major ionic currents and to use the data to simulate action potentials (APs) recorded from PCs. Light microscopy was used to isolate and identify PCs from apical and septal cells. Current and voltage clamp techniques were used to record APs and whole cell currents. We then simulated a PC AP on the basis of our experimental data. APs recorded from PCs were significantly longer than those recorded from ventricular cells. The prominent plateau phase of the PC AP was very negative (≈-40 mV). Spontaneous activity was observed only in PCs. The inward rectifier current demonstrated no significant differences compared to ventricular myocytes (VMs). However, sodium current density was larger, and the voltage-gated potassium current density was significantly less in PCs compared with myocytes. T-type Ca(2+) currents (I(Ca,T)) were present in PCs but not VMs. Computer simulations suggest that I(Ca,T) and cytosolic calcium diffusion significantly modulate AP profile recorded in PCs, as compared to VMs. Our study provides the first comprehensive ionic profile of murine PCs. The data show unique features of PC ionic mechanisms that govern its excitation process. Experimental data and numerical modeling results suggest that a smaller voltage-gated potassium current and the presence of I(Ca,T) are important determinants of the longer and relatively negative plateau phase of the APs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Fine Tuned Modulation of the Motor System by Adjectives Expressing Positive and Negative Properties

ERIC Educational Resources Information Center

Gough, P. M.; Campione, G. C.; Buccino, G.

2013-01-01

Using transcranial magnetic stimulation (TMS), motor evoked potentials (MEPs) were recorded from two antagonistic muscles, the first dorsal interosseus (FDI) of the hand and the extensor communis digitorum (EC) of the forearm. FDI is involved in grasping actions and EC in releasing. TMS pulses were delivered while participants were reading…

A Case Study of Leadership Development in Action: The UJIA Ashdown Fellowship 2000-2007

ERIC Educational Resources Information Center

Winston, Lira

2009-01-01

Purpose: The United Jewish Israel Appeal Ashdown Fellowship was launched in 2000 with the aim of creating high quality leadership for educational organisations in the British Jewish community. It sought to develop talented and committed people who demonstrated leadership potential. The purpose of this paper is to record the narrative of the…

Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact

PubMed Central

Kent, A R; Grill, W M

2012-01-01

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the selection of stimulus parameters is a clinical burden and often yields sub-optimal outcomes for patients. Measurement of electrically evoked compound action potentials (ECAPs) during DBS could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulus parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1,000 to 5,000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 μs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters. PMID:22510375

On-chip, multisite extracellular and intracellular recordings from primary cultured skeletal myotubes

PubMed Central

Rabieh, Noha; Ojovan, Silviya M.; Shmoel, Nava; Erez, Hadas; Maydan, Eilon; Spira, Micha E.

2016-01-01

In contrast to the extensive use of microelectrode array (MEA) technology in electrophysiological studies of cultured neurons and cardiac muscles, the vast field of skeletal muscle research has yet to adopt the technology. Here we demonstrate an empowering MEA technology for high quality, multisite, long-term electrophysiological recordings from cultured skeletal myotubes. Individual rat skeletal myotubes cultured on micrometer sized gold mushroom-shaped microelectrode (gMμE) based MEA tightly engulf the gMμEs, forming a high seal resistance between the myotubes and the gMμEs. As a consequence, spontaneous action potentials generated by the contracting myotubes are recorded as extracellular field potentials with amplitudes of up to 10 mV for over 14 days. Application of a 10 ms, 0.5–0.9 V voltage pulse through the gMμEs electroporated the myotube membrane, and transiently converted the extracellular to intracellular recording mode for 10–30 min. In a fraction of the cultures stable attenuated intracellular recordings were spontaneously produced. In these cases or after electroporation, subthreshold spontaneous potentials were also recorded. The introduction of the gMμE-MEA as a simple-to-use, high-quality electrophysiological tool together with the progress made in the use of cultured human myotubes opens up new venues for basic and clinical skeletal muscle research, preclinical drug screening, and personalized medicine. PMID:27812002

Ethanol exposure in early adolescence inhibits intrinsic neuronal plasticity via sigma-1 receptor activation in hippocampal CA1 neurons

PubMed Central

Sabeti, Jilla

2011-01-01

Background We demonstrated previously that rats exposed to chronic intermittent ethanol (CIE) vapors in early adolescence show increased magnitudes of long-term potentiation (LTP) of excitatory transmission when recorded at dendritic synapses in hippocampus. Large amplitude LTP following CIE exposure is mediated by sigma-1 receptors; however, not yet addressed is the role of sigma-1 receptors in modulating the intrinsic properties of neurons to alter their action potential firing during LTP. Methods Activity-induced plasticity of spike firing was investigated using rat hippocampal slice recordings to measure changes in both field excitatory postsynaptic potentials (fEPSPs) and population spikes (pop. spikes) concomitantly at dendritic inputs and soma of CA1 pyramidal neurons, respectively. Results We observed unique modifications in plasticity of action potential firing in hippocampal slices from CIE exposed adolescent rats, where the induction of large amplitude LTP by 100 Hz stimulations was accompanied by reduced CA1 neuronal excitability—reflected as decreased pop. spike efficacy and impaired activity-induced fEPSP-to-spike (E-S) potentiation. By contrast, LTP induction in ethanol-naïve control slices resulted in increased spike efficacy and robust E-S potentiation. E-S potentiation impairments emerged at 24 hr after CIE treatment cessation, but not before the alcohol withdrawal period, and were restored with bath-application of the sigma-1 receptor selective antagonist BD1047, but not the NMDA receptor antagonist D-AP5. Further evidence revealed a significantly shortened somatic fEPSP time course in adolescent CIE-withdrawn hippocampal slices during LTP; however, paired-pulse data show no apparent correspondence between E-S dissociation and altered recurrent feedback inhibition. Conclusions Results here suggest that acute withdrawal from adolescent CIE exposure triggers sigma-1 receptors that act to depress the efficacy of excitatory inputs in triggering action potentials during LTP. Such withdrawal-induced depression of E-S plasticity in hippocampus likely entails sigma-1 receptor modulation of one or several voltage-gated ion channels controlling the neuronal input-output dynamics. PMID:21314692

Superfund Record of Decision (EPA Region 8): Anaconda Smelter site, (Operable Unit 11 - Flue Dust), Deer Lodge County, Anaconda, MT. (Second remedial action), September 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-09-23

The 6,000-acre Anaconda Smelter site is a former copper and ore processing facility in Deer Lodge County, Montana. Land use in the area is predominantly residential. The site is bounded on the north and east, respectively, by the Warm Springs Creek and Mill Creek, both of which are potential sources of drinking water. From 1884 until 1980 when activities ceased, the site was used for ore processing and smelting operations. In 1988, EPA conducted an investigation to determine the nature and extent of the flue dust contamination. A 1988 ROD addressed the Mill Creek Operable Unit (OU15) and documented themore » relocation of residents from the community surrounding the smelter site as the selected remedial action. The Record of Decision (ROD) addresses the Flue Dust Operable Unit (OU11). The primary contaminants of concern affecting this site from the flue dust materials are metals including arsenic, cadmium, and lead. The selected remedial action for the site is included.« less

Harm avoiders suppress motor resonance to observed immoral actions

PubMed Central

Candidi, Matteo; Sforza, Anna Laura; Aglioti, Salvatore Maria

2015-01-01

Motor resonance (MR) contingent upon action observation is thought to occur largely automatically. Although recent studies suggest that this process is not completely impervious to top-down modulations, much less is known on the possible role of the moral connotation of observed action goal in modulating MR. Here, we explored whether observing actions with different moral connotations modulates MR and whether any modulation depends on the onlookers’ personality. To this aim, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation from hand muscles of participants who were watching images of a model performing hand actions with the same postures and low-level goals (i.e. grasping an object) but with different moral connotations (‘stealing a wallet’ vs ‘picking up a notepaper’). Participants’ personality traits were measured using the temperament and character inventory. Results show a selective suppression of corticospinal excitability during observation of immoral actions in individuals with high scores in harm avoidance, a personality trait characterized by excessive worrying and fearfulness. Thus, a combination of dispositional (personality traits) and situational (morality of an action) variables appears to influence MR with the observed actions. PMID:24526183

Risk of punishment influences discrete and coordinated encoding of reward-guided actions by prefrontal cortex and VTA neurons

PubMed Central

Park, Junchol

2017-01-01

Actions motivated by rewards are often associated with risk of punishment. Little is known about the neural representation of punishment risk during reward-seeking behavior. We modeled this circumstance in rats by designing a task where actions were consistently rewarded but probabilistically punished. Spike activity and local field potentials were recorded during task performance simultaneously from VTA and mPFC, two reciprocally connected regions implicated in reward-seeking and aversive behaviors. At the single unit level, we found that ensembles of putative dopamine and non-dopamine VTA neurons and mPFC neurons encode the relationship between action and punishment. At the network level, we found that coherent theta oscillations synchronize VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions. This synchrony declined as a function of punishment probability, suggesting that during reward-seeking actions, risk of punishment diminishes VTA-driven neural synchrony between the two regions. PMID:29058673

High-Bandwidth Atomic Force Microscopy Reveals A Mechanical spike Accompanying the Action Potential in mammalian Nerve Terminals

NASA Astrophysics Data System (ADS)

Salzberg, Brian M.

2008-03-01

Information transfer from neuron to neuron within nervous systems occurs when the action potential arrives at a nerve terminal and initiates the release of a chemical messenger (neurotransmitter). In the mammalian neurohypophysis (posterior pituitary), large and rapid changes in light scattering accompany secretion of transmitter-like neuropeptides. In the mouse, these intrinsic optical signals are intimately related to the arrival of the action potential (E-wave) and the release of arginine vasopressin and oxytocin (S-wave). We have used a high bandwidth (20 kHz) atomic force microscope (AFM) to demonstrate that these light scattering signals are associated with changes in nerve terminal volume, detected as nanometer-scale movements of a cantilever positioned on top of the neurohypophysis. The most rapid mechanical response, the ``spike'', has duration comparable to that of the action potential (˜2 ms) and probably reflects an increase in terminal volume due to H2O movement associated with Na^+-influx. Elementary calculations suggest that two H2O molecules accompanying each Na^+-ion could account for the ˜0.5-1.0 å increase in the diameter of each terminal during the action potential. Distinguishable from the mechanical ``spike'', a slower mechanical event, the ``dip'', represents a decrease in nerve terminal volume, depends upon Ca^2+-entry, as well as on intra-terminal Ca^2+-transients, and appears to monitor events associated with secretion. A simple hypothesis is that this ``dip'' reflects the extrusion of the dense core granule that comprises the secretory products. These dynamic high bandwidth AFM recordings are the first to monitor mechanical events in nervous systems and may provide novel insights into the mechanism(s) by which excitation is coupled to secretion at nerve terminals.

(2R,3S,2”R,3”R)-manniflavanone, a new gastrointestinal smooth muscle L-type calcium channel inhibitor, which underlies the spasmolytic properties of Garcinia buchananii stem bark extract

PubMed Central

Balemba, Onesmo B.; Stark, Timo D.; Lösch, Sofie; Patterson, Savannah; McMillan, John S.; Mawe, Gary M.; Hofmann, Thomas

2014-01-01

Garcinia buchananii Baker stem bark extract (GBB) is a traditional medication of diarrhea and dysentery in sub-Saharan Africa. It is believed that GBB causes gastrointestinal smooth muscle relaxation. The aim of this study was to determine whether GBB has spasmolytic actions and identify compounds underlying these actions. Calcium (Ca2+) imaging was used to analyze the effect of GBB on Ca2+ flashes and Ca2+ waves in guinea pig gallbladder and distal colon smooth muscle. Intracellular microelectrode recording was used to determine the effect of GBB, six fractions of GBB, M1–5 and M7, and (2R,3S,2”R,3”R)-manniflavanone, a compound isolated from M3 on action potentials in gallbladder smooth muscle. The technique was also used to analyze the effect of GBB, M3, and (2R,3S,2”R,3”R)-manniflavanone on action potentials in the circular muscle of mouse and guinea pig distal colons, and the effect of GBB and (2R,3S,2”R,3”R)-manniflavanone on slow waves in porcine ileum. GBB inhibited Ca2+ flashes and Ca2+ waves. GBB, M3 and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials. L-type Ca2+ channel activator Bay K 8644 increased the discharge of action potentials in mouse colon but did not trigger or increase action potentials in the presence of GBB and (2R,3S,2”R,3”R)-manniflavanone. GBB and (2R,3S,2”R,3”R)-manniflavanone inhibited action potentials in the presence of Bay K 8644. GBB and (2R,3S,2”R,3”R)-manniflavanone reduced the amplitude but did not alter the frequency of slow waves in the porcine ileum. In conclusion, GBB and (2R,3S,2”R,3”R)-manniflavanone relax smooth muscle by inhibiting L-type Ca2+ channels, thus have potential for use as therapies of gastrointestinal smooth muscle spasms, and arrhythmias. PMID:26081368

Spatial Resolution Requirements for Accurate Identification of Drivers of Atrial Fibrillation

PubMed Central

Roney, Caroline H.; Cantwell, Chris D.; Bayer, Jason D.; Qureshi, Norman A.; Lim, Phang Boon; Tweedy, Jennifer H.; Kanagaratnam, Prapa; Vigmond, Edward J.; Ng, Fu Siong

2017-01-01

Background— Recent studies have demonstrated conflicting mechanisms underlying atrial fibrillation (AF), with the spatial resolution of data often cited as a potential reason for the disagreement. The purpose of this study was to investigate whether the variation in spatial resolution of mapping may lead to misinterpretation of the underlying mechanism in persistent AF. Methods and Results— Simulations of rotors and focal sources were performed to estimate the minimum number of recording points required to correctly identify the underlying AF mechanism. The effects of different data types (action potentials and unipolar or bipolar electrograms) and rotor stability on resolution requirements were investigated. We also determined the ability of clinically used endocardial catheters to identify AF mechanisms using clinically recorded and simulated data. The spatial resolution required for correct identification of rotors and focal sources is a linear function of spatial wavelength (the distance between wavefronts) of the arrhythmia. Rotor localization errors are larger for electrogram data than for action potential data. Stationary rotors are more reliably identified compared with meandering trajectories, for any given spatial resolution. All clinical high-resolution multipolar catheters are of sufficient resolution to accurately detect and track rotors when placed over the rotor core although the low-resolution basket catheter is prone to false detections and may incorrectly identify rotors that are not present. Conclusions— The spatial resolution of AF data can significantly affect the interpretation of the underlying AF mechanism. Therefore, the interpretation of human AF data must be taken in the context of the spatial resolution of the recordings. PMID:28500175

Activation of Ih and TTX-sensitive sodium current at subthreshold voltages during CA1 pyramidal neuron firing

PubMed Central

Yamada-Hanff, Jason

2015-01-01

We used dynamic clamp and action potential clamp techniques to explore how currents carried by tetrodotoxin-sensitive sodium channels and HCN channels (Ih) regulate the behavior of CA1 pyramidal neurons at resting and subthreshold voltages. Recording from rat CA1 pyramidal neurons in hippocampal slices, we found that the apparent input resistance and membrane time constant were strongly affected by both conductances, with Ih acting to decrease apparent input resistance and time constant and sodium current acting to increase both. We found that both Ih and sodium current were active during subthreshold summation of artificial excitatory postsynaptic potentials (EPSPs) generated by dynamic clamp, with Ih dominating at less depolarized voltages and sodium current at more depolarized voltages. Subthreshold sodium current—which amplifies EPSPs—was most effectively recruited by rapid voltage changes, while Ih—which blunts EPSPs—was maximal for slow voltage changes. The combined effect is to selectively amplify rapid EPSPs. We did similar experiments in mouse CA1 pyramidal neurons, doing voltage-clamp experiments using experimental records of action potential firing of CA1 neurons previously recorded in awake, behaving animals as command voltages to quantify flow of Ih and sodium current at subthreshold voltages. Subthreshold sodium current was larger and subthreshold Ih was smaller in mouse neurons than in rat neurons. Overall, the results show opposing effects of subthreshold sodium current and Ih in regulating subthreshold behavior of CA1 neurons, with subthreshold sodium current prominent in both rat and mouse CA1 pyramidal neurons and additional regulation by Ih in rat neurons. PMID:26289465

In vitro Neurons in Mammalian Cortical Layer 4 Exhibit Intrinsic Oscillatory Activity in the 10- to 50-Hz Frequency Range

NASA Astrophysics Data System (ADS)

Llinas, Rodolfo R.; Grace, Anthony A.; Yarom, Yosef

1991-02-01

We report here the presence of fast subthreshold oscillatory potentials recorded in vitro from neurons within layer 4 of the guinea pig frontal cortex. Two types of oscillatory neurons were recorded: (i) One type exhibited subthreshold oscillations whose frequency increased with membrane depolarization and encompassed a range of 10-45 Hz. Action potentials in this type of neuron demonstrated clear after-hyperpolarizations. (ii) The second type of neuron was characterized by narrow-frequency oscillations near 35-50 Hz. These oscillations often outlasted the initiating depolarizing stimulus. No calcium component could be identified in their action potential. In both types of cell the subthreshold oscillations were tetrodotoxin-sensitive, indicating that the depolarizing phase of the oscillation was generated by a voltage-dependent sodium conductance. The initial depolarizing phase was followed by a potassium conductance responsible for the falling phase of the oscillatory wave. In both types of cell, the subthreshold oscillation could trigger spikes at the oscillatory frequency, if the membrane was sufficiently depolarized. Combining intracellular recordings with Lucifer yellow staining showed that the narrow-frequency oscillatory activity was produced by a sparsely spinous interneuron located in layer 4 of the cortex. This neuron has extensive local axonal collaterals that ramify in layers 3 and 4 such that they may contribute to the columnar synchronization of activity in the 40- to 50-Hz range. Cortical activity in this frequency range has been proposed as the basis for the "conjunctive properties" of central nervous system networks.

Recording Field Potentials From Zebrafish Larvae During Escape Responses

PubMed Central

Monesson-Olson, Bryan D.; Troconis, Eileen L.; Trapani, Josef G.

2014-01-01

Among vertebrates, startle responses are a ubiquitous method for alerting, and avoiding or escaping from alarming or dangerous stimuli. In zebrafish larvae, fast escape behavior is easily evoked through either acoustic or tactile stimuli. For example, a light touch to the head will excite trigeminal neurons that in turn excite a large reticulospinal neuron in the hindbrain called the Mauthner cell (M-cell). The M-cell action potential then travels down the contralateral trunk of the larva exciting motoneurons, which subsequently excite the entire axial musculature, producing a large amplitude body bend away from the source of the stimulus. This body conformation is known as the “C-bend” due to the shape of the larva during the behavior. As a result of the semi-synchronized activation of the M-cell, the population of motor neurons, and the axial trunk muscles, a large field potential is generated and can be recorded from free-swimming or fixed-position larvae. Undergraduate laboratories that record field potentials during escape responses in larval zebrafish are relatively simple to setup and allow students to observe and study the escape reflex circuit. Furthermore, by testing hypotheses, analyzing data and writing journal-style laboratory reports, students have multiple opportunities to learn about many neuroscience topics including vertebrate reflexes; sensory transduction; synaptic-, neuro-, and muscle-physiology; the M-cell mediated escape response; and the zebrafish as a model organism. Here, we detail the equipment, software, and recording setup necessary to observe field potentials in an undergraduate teaching lab. Additionally, we discuss potential advanced laboratory exercises and pedagogical outcomes. Finally, we note possible low-cost alternatives for recording field potentials. PMID:25565920

5 CFR 1630.12 - Action on request to amend a record.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATIONS § 1630.12 Action on request to amend a record. (a) For TSP records, the record keeper will... chart in § 1630.11, within 10 work days. Requests received by the record keeper which are to be decided by the current or former employing agency will be sent to that agency by the record keeper within 3...

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dexterous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

DTIC Science & Technology

2017-10-01

potentials or multi-action potential activity from residual peripheral nerve while patient intends movements of amputated hand/arm Subtask 3.1: Mapping of...neural activity (Months 4 – 36) • Patients will be asked to intend a number of individual finger and multiple finger flexion, extension, adduction...intended movements. We will map the different intended movements onto the neural activity recorded on the electrodes of the micro-electrode array

Sub-millisecond closed-loop feedback stimulation between arbitrary sets of individual neurons

PubMed Central

Müller, Jan; Bakkum, Douglas J.; Hierlemann, Andreas

2012-01-01

We present a system to artificially correlate the spike timing between sets of arbitrary neurons that were interfaced to a complementary metal–oxide–semiconductor (CMOS) high-density microelectrode array (MEA). The system features a novel reprogrammable and flexible event engine unit to detect arbitrary spatio-temporal patterns of recorded action potentials and is capable of delivering sub-millisecond closed-loop feedback of electrical stimulation upon trigger events in real-time. The relative timing between action potentials of individual neurons as well as the temporal pattern among multiple neurons, or neuronal assemblies, is considered an important factor governing memory and learning in the brain. Artificially changing timings between arbitrary sets of spiking neurons with our system could provide a “knob” to tune information processing in the network. PMID:23335887

Active signal conduction through the sensory dendrite of a spider mechanoreceptor neuron.

PubMed

Gingl, Ewald; French, Andrew S

2003-07-09

Rapid responses to sensory stimulation are crucial for survival. This must be especially true for mechanical stimuli containing temporal information, such as vibration. Sensory transduction occurs at the tips of relatively long sensory dendrites in many mechanoreceptors of both vertebrates and invertebrates, but little is known about the electrical properties of these crucial links between transduction and action potential generation. The VS-3 slit-sense organ of the spider Cupiennius salei contains bipolar mechanosensory neurons that allow voltage-clamp recording from the somata, whereas mechanotransduction occurs at the tips of 100- to 200-microm-long sensory dendrites. We studied the properties of VS-3 sensory dendrites using three approaches. Voltage-jump experiments measured the spread of voltage outward from the soma by observing total mechanically transduced charge recovered at the soma as a function of time after a voltage jump. Frequency-response measurements between pseudorandom mechanical stimulation and somatic membrane potential estimated the passive cable properties of the dendrite for voltage spread in the opposite direction. Both of these sets of data indicated that the dendritic cable would significantly attenuate and retard a passively propagated receptor potential. Finally, current-clamp observations of receptor potentials and action potentials indicated that action potentials normally start at the distal dendrites and propagate regeneratively to the soma, reducing the temporal delay of passive conduction.

A 64-channel ultra-low power system-on-chip for local field and action potentials recording

NASA Astrophysics Data System (ADS)

Rodríguez-Pérez, Alberto; Delgado-Restituto, Manuel; Darie, Angela; Soto-Sánchez, Cristina; Fernández-Jover, Eduardo; Rodríguez-Vázquez, Ángel

2015-06-01

This paper reports an integrated 64-channel neural recording sensor. Neural signals are acquired, filtered, digitized and compressed in the channels. Additionally, each channel implements an auto-calibration mechanism which configures the transfer characteristics of the recording site. The system has two transmission modes; in one case the information captured by the channels is sent as uncompressed raw data; in the other, feature vectors extracted from the detected neural spikes are released. Data streams coming from the channels are serialized by an embedded digital processor. Experimental results, including in vivo measurements, show that the power consumption of the complete system is lower than 330μW.

United States Air Force 611th Civil Engineer Squadron, Elmendorf AFB, Alaska. Final engineering evaluation/cost analysis: Petroleum, oil, and lubricants area, Galena Airport, Alaska

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-02-05

This decision document presents the selected removal action for the Installation Restoration Program (IRP) site ST005, otherwise known as the POL Tank Farm, at Galena Airport, Alaska. This decision is based on the administrative record for this site, specifically the draft Remedial Investigation Report (March 1995) and the Treatability Study Report (January 1995) (PB95-225314). The information from these documents is summarized, along with an analysis of potential removal action alternatives in the Engineering Evaluation/Cost Analysis (EE/CA).

10 CFR 1008.10 - Action in response to a request for correction or amendment of records.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Action in response to a request for correction or amendment of records. 1008.10 Section 1008.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) RECORDS MAINTAINED ON INDIVIDUALS (PRIVACY ACT) Requests for Access or Amendment § 1008.10 Action in response to a...

10 CFR 1008.10 - Action in response to a request for correction or amendment of records.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Action in response to a request for correction or amendment of records. 1008.10 Section 1008.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) RECORDS MAINTAINED ON INDIVIDUALS (PRIVACY ACT) Requests for Access or Amendment § 1008.10 Action in response to a...

Simultaneous recording of the action potential and its whole-cell associated ion current on NG108-15 cells cultured over a MWCNT electrode

NASA Astrophysics Data System (ADS)

Morales-Reyes, I.; Seseña-Rubfiaro, A.; Acosta-García, M. C.; Batina, N.; Godínez-Fernández, R.

2016-08-01

It is well known that, in excitable cells, the dynamics of the ion currents (I i) is extremely important to determine both the magnitude and time course of an action potential (A p). To observe these two processes simultaneously, we cultured NG108-15 cells over a multi-walled carbon nanotubes electrode (MWCNTe) surface and arranged a two independent Patch Clamp system configuration (Bi-Patch Clamp). The first system was used in the voltage or current clamp mode, using a glass micropipette as an electrode. The second system was modified to connect the MWCNTe to virtual ground. While the A p was recorded through the micropipette electrode, the MWCNTe was used to measure the underlying whole-cell current. This configuration allowed us to record both the membrane voltage (V m) and the current changes simultaneously. Images acquired by atomic force microscopy (AFM) and scanning electron microscopy (SEM) indicate that cultured cells developed a complex network of neurites, which served to establish the necessary close contact and strong adhesion to the MWCNTe surface. These features were a key factor to obtain the recording of the whole-cell I i with a high signal to noise ratio (SNR). The experimental results were satisfactorily reproduced by a theoretical model developed to simulate the proposed system. Besides the contribution to a better understanding of the fundamental mechanisms involved in cell communication, the developed method could be useful in cell physiology studies, pharmacology and diseases diagnosis.

40 CFR 63.9818 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... of each occurrence, measurement, maintenance, corrective action, report, or record. (c) You must keep each record onsite for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or record, according to § 63.10(b)(1). You may keep the records offsite for the...

40 CFR 63.4531 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... each occurrence, measurement, maintenance, corrective action, report, or record. (c) You must keep each record on-site for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or record according to § 63.10(b)(1). You may keep the records off-site for the...

40 CFR 63.2863 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... each occurrence, measurement, maintenance, corrective action, report, or record. (c) You must keep each record on-site for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or record, in accordance with § 3.10(b)(1). You can keep the records off-site for...

40 CFR 63.9933 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... of each occurrence, measurement, maintenance, corrective action, report, or record. (c) You must keep each record on site for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or record according to § 63.10(b)(1). You can keep the records off site for the...

40 CFR 63.11442 - What are the recordkeeping requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

...), you must keep each record for 5 years following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (d) You must keep each record onsite for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or record, according to...

18 CFR 375.102 - Custody and authentication of Commission records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... authentication of Commission records. 375.102 Section 375.102 Conservation of Power and Water Resources FEDERAL... Provisions § 375.102 Custody and authentication of Commission records. (a) Custody of official records. (1...) Authentication of Commission action. All orders and other actions of the Commission shall be authenticated or...

Corrective Action Investigation Plan for Corrective Action Unit 168: Areas 25 and 26 Contaminated Materials and Waste Dumps, Nevada Test Site, Nevada (Rev. 0) includes Record of Technical Change No. 1 (dated 8/28/2002), Record of Technical Change No. 2 (dated 9/23/2002), and Record of Technical Change No. 3 (dated 6/2/2004)

DOE Office of Scientific and Technical Information (OSTI.GOV)

U.S. Department of Energy, National Nuclear Security Administration Nevada

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit 168 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 168 consists of a group of twelve relatively diverse Corrective Action Sites (CASs 25-16-01, Construction Waste Pile; 25-16-03, MX Construction Landfill; 25-19-02, Waste Disposal Site; 25-23-02, Radioactive Storage RR Cars; 25-23-18, Radioactive Material Storage; 25-34-01, NRDS Contaminated Bunker; 25-34-02, NRDS Contaminated Bunker; CAS 25-23-13, ETL - Lab Radioactive Contamination; 25-99-16, USW G3;more » 26-08-01, Waste Dump/Burn Pit; 26-17-01, Pluto Waste Holding Area; 26-19-02, Contaminated Waste Dump No.2). These CASs vary in terms of the sources and nature of potential contamination. The CASs are located and/or associated wit h the following Nevada Test Site (NTS) facilities within three areas. The first eight CASs were in operation between 1958 to 1984 in Area 25 include the Engine Maintenance, Assembly, and Disassembly Facility; the Missile Experiment Salvage Yard; the Reactor Maintenance, Assembly, and Disassembly Facility; the Radioactive Materials Storage Facility; and the Treatment Test Facility Building at Test Cell A. Secondly, the three CASs located in Area 26 include the Project Pluto testing area that operated from 1961 to 1964. Lastly, the Underground Southern Nevada Well (USW) G3 (CAS 25-99-16), a groundwater monitoring well located west of the NTS on the ridgeline of Yucca Mountain, was in operation during the 1980s. Based on site history and existing characterization data obtained to support the data quality objectives process, contaminants of potential concern (COPCs) for CAU 168 are primarily radionuclide; however, the COPCs for several CASs were not defined. To address COPC uncertainty, the analytical program for most CASs will include volatile organic compounds, semivolatile organic compounds, Resource Conservation and Recovery Act metals, total petroleum hydrocarbons, polychlorinated biphenyls, and radionuclides. Upon reviewing historical data and current site conditions, it has been determined that no further characterization is required at USW G3 (CAS 25-99-16) to select the appropriate corrective action. A cesium-137 source was encased in cement within the vadous zone during the drilling of the well (CAS 25-99-16). A corrective action of closure in place with a land-use restriction for drilling near USW G3 is appropriate. This corrective action will be documented in the Corrective Action Decision Document (CADD) for CAU 168. The results of the remaining field investigation will support a defensible evaluation of corrective action alternatives for the other CASs within CAU 168 in this CADD.« less

Events at blood collection area due to nonconforming blood bags and plateletpheresis kits: need for timely corrective and preventive actions.

PubMed

Verma, Anupam; Sachan, Deepti; Elhence, Priti; Pandey, Hem; Dubey, Anju

2012-07-01

Good blood banking practice requires that every effort should be made to detect any deviation or defect in blood bank products and to identify any potential risk to blood donor or recipient(s). We report the findings of an exercise that provide an insight into why feedback from the user side is crucial. Various events involving blood bags and plateletpheresis kits and the corresponding appropriate actions instituted for remedial measures were recorded. These scattered events were recorded for 6 months following the use of a new batch of improved blood bags with add-on features. Several events related to plateletpheresis kits from three different manufacturers were also recorded for 1 year. The affected blood bags were utilized with no untoward incident. The complaint was closed following satisfactory response from the blood bag manufacturing company that acted in a timely manner in addressing the root causes of the problems. However, corrective and preventive actions (CAPA) could not be implemented for plateletpheresis kits. The rate of undesirable events was higher with plateletpheresis kits as compared with whole blood bags (1.75% vs. 0.06%). As defects or deviations that trigger the need for CAPA can stem from numerous sources, it is important to clearly identify and document the problems and level of risk so that appropriate investigations can be instituted and remedial actions can be taken in a timely manner. This study demonstrates the usefulness of a quality initiative to collate and analyze blood product faults in conjunction with blood product manufacturers. © 2012 American Association of Blood Banks.

K+ currents underlying the action of endothelium-derived hyperpolarizing factor in guinea-pig, rat and human blood vessels

PubMed Central

Coleman, H A; Tare, Marianne; Parkington, Helena C

2001-01-01

Membrane currents attributed to endothelium-derived hyperpolarizing factor (EDHF) were recorded in short segments of submucosal arterioles of guinea-pigs using single microelectrode voltage clamp. The functional responses of arterioles and human subcutaneous, rat hepatic and guinea-pig coronary arteries were also assessed as changes in membrane potential recorded simultaneously with contractile activity. The current-voltage (I-V) relationship for the conductance due to EDHF displayed outward rectification with little voltage dependence. Components of the current were blocked by charybdotoxin (30-60 nM) and apamin (0.25-0.50 μM), which also blocked hyperpolarization and prevented EDHF-induced relaxation. The EDHF-induced current was insensitive to Ba2+ (20-100 μM) and/or ouabain (1 μM to 1 mM). In human subcutaneous arteries and guinea-pig coronary arteries and submucosal arterioles, the EDHF-induced responses were insensitive to Ba2+ and/or ouabain. Increasing [K+]o to 11-21 mM evoked depolarization under conditions in which EDHF evoked hyperpolarization. Responses to ACh, sympathetic nerve stimulation and action potentials were indistinguishable between dye-labelled smooth muscle and endothelial cells in arterioles. Action potentials in identified endothelial cells were always associated with constriction of the arterioles. 18β-Glycyrrhetinic acid (30 μM) and carbenoxolone (100 μM) depolarized endothelial cells by 31 ± 6 mV (n = 7 animals) and 33 ± 4 mV (n = 5), respectively, inhibited action potentials in smooth muscle and endothelial cells and reduced the ACh-induced hyperpolarization of endothelial cells by 56 and 58 %, respectively. Thus, activation of outwardly rectifying K+ channels underlies the hyperpolarization and relaxation due to EDHF. These channels have properties similar to those of intermediate conductance (IKCa) and small conductance (SKCa) Ca2+-activated K+ channels. Strong electrical coupling between endothelial and smooth muscle cells implies that these two layers function as a single electrical syncytium. The non-specific effects of glycyrrhetinic acid precludes its use as an indicator of the involvement of gap junctions in EDHF-attributed responses. These conclusions are likely to apply to a variety of blood vessels including those of humans. PMID:11230509

Superfund record of decision (EPA Region 5): Skinner Landfill, West Chester, OH, June 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-06-04

The decision document presents the selected final remedial action for the Skinner Landfill site in West Chester, Ohio. The remedy is the second and final of two operable units for this site. The first operable unit addressed immediate site concerns, through the construction of a fence around the contaminated area, and by offering an alternate supply of drinking water to the potentially affected users of groundwater. This final operable unit addresses potential future migration of site contaminants into the groundwater and will limit the potential for direct exposure of site contaminants to humans through source control measures.

[A functional statistical analysis of the action potentials in the brain multineuronal activity of waking cats].

PubMed

Merzhanova, G Kh; Porada, I

1990-01-01

In the present work a method is substantiated of the correction of singled out impulses series by identification of parameters of neurones discharges (PD) during a long period of recording (up to 120 days) of the neuronal activity by means of chronically implanted nichrome semimicroelectrode in different brain part of alert cats.

Why Are Macros Not Used? A Brief Review and an Approach for Improving Training

ERIC Educational Resources Information Center

Yechiam, Eldad

2006-01-01

Macros are programming scripts that can be generated by recording users' actions. It appears that despite their potential for reducing monotonous work, they are under-used by non-programmers. The present paper reviews the literature on the use of macros. Included is an original study that examines the effect of adding the "search and replace"…

Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory.

PubMed

Hasselmo, Michael E; Giocomo, Lisa M; Brandon, Mark P; Yoshida, Motoharu

2010-12-31

Understanding the mechanisms of episodic memory requires linking behavioral data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. Copyright © 2010 Elsevier B.V. All rights reserved.

Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory

PubMed Central

Hasselmo, Michael E.; Giocomo, Lisa M.; Yoshida, Motoharu

2010-01-01

Understanding the mechanisms of episodic memory requires linking behavioural data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within these brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. PMID:20018213

Measurement of the Perception of Control during Continuous Movement using Electroencephalography

PubMed Central

Wen, Wen; Yamashita, Atsushi; Asama, Hajime

2017-01-01

“Sense of control” refers to the subjective feeling of control over external events. Numerous neuropsychological studies have investigated the neural basis of the sense of control during action performance; however, most previous studies have focused on responses to a single discrete action outcome rather than real-time processing of action-outcome sequences. In the present study, we aimed to identify whether certain patterns of brain activation are associated with the perceived control during continuous movement. We recorded electroencephalography (EEG) signals while participants continuously moved a right-handed mouse in an attempt to control multiple visual stimuli. When participants perceived a sense of control over the stimuli, we observed a positive potential approximately 550 ms after the onset of movement, while no similar potential was observed when participants reported a lack of control. The appearance of this potential was consistent with the time window of awareness of control in a behavioral test using the same task, and likely reflected the explicit allocation of attention to control. Moreover, we found that the alpha-mu rhythm, which is linked to sensorimotor processing, was significantly suppressed after participants came to a conclusion regarding the level of control, regardless of whether control or lack of control was perceived. In summary, our results suggest that the late positive potential after the onset of the movement and the suppression of alpha-mu rhythm can be used as markers of the perception of control during continuous action performance and feedback monitoring. PMID:28798677

The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials.

PubMed

Boothe, Sean D; Myers, Jackson D; Pok, Seokwon; Sun, Junping; Xi, Yutao; Nieto, Raymond M; Cheng, Jie; Jacot, Jeffrey G

2016-12-01

The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa. Using whole-cell patch clamping, action potentials and L-type calcium currents were recorded. Cardiomyocytes cultured on hydrogels with a 9 kPa elastic modulus, similar to that of native myocardium, had the longest action potential duration. Additionally, the voltage at maximum calcium flux significantly decreased in cardiomyocytes on hydrogels with an elastic modulus higher than 9 kPa, and the mean inactivation voltage decreased with increasing stiffness. Interestingly, the expression of the L-type calcium channel subunit α gene and channel localization did not change with stiffness. Substrate stiffness significantly affects action potential length and calcium flux in cultured neonatal rat cardiomyocytes in a manner that may be unrelated to calcium channel expression. These results may explain functional differences in cardiomyocytes resulting from changes in the elastic modulus of the extracellular matrix, as observed during embryonic development, in ischemic regions of the heart after myocardial infarction, and during dilated cardiomyopathy.

Dorsal–Ventral Gradient for Neuronal Plasticity in the Embryonic Spinal Cord

PubMed Central

Pineda, Ricardo H.; Ribera, Angeles B.

2008-01-01

Within the developing Xenopus spinal cord, voltage-gated potassium (Kv) channel genes display different expression patterns, many of which occur in opposing dorsal–ventral gradients. Regional differences in Kv gene expression would predict different patterns of potassium current (IKv) regulation. However, during the first 24 h of postmitotic differentiation, all primary spinal neurons undergo a temporally coordinated upregulation of IKv density that shortens the duration of the action potential. Here, we tested whether spinal neurons demonstrate regional differences in IKv regulation subsequent to action potential maturation. We show that two types of neurons, I and II, can be identified in culture on the basis of biophysical and pharmacological properties of IKv and different firing patterns. Chronic increases in extracellular potassium, a signature of high neuronal activity, do not alter excitability properties of either neuron type. However, elevating extracellular potassium acutely after the period of action potential maturation leads to different changes in membrane properties of the two types of neurons. IKv of type I neurons gains sensitivity to the blocker XE991, whereas type II neurons increase IKv density and fire fewer action potentials. Moreover, by recording from neurons in vivo, we found that primary spinal neurons can be identified as either type I or type II. Type I neurons predominate in dorsal regions, whereas type II neurons localize to ventral regions. The findings reveal a dorsal–ventral gradient for IKv regulation and a novel form of neuronal plasticity in spinal cord neurons. PMID:18385340

40 CFR 63.6012 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., measurement, maintenance, corrective action, report, or record. (c) You must keep each record on site for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or...

Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernandez, Maria G. H.

2010-05-31

The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours andmore » at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).« less

Differences in transient outward currents of feline endocardial and epicardial myocytes.

PubMed

Furukawa, T; Myerburg, R J; Furukawa, N; Bassett, A L; Kimura, S

1990-11-01

Whole-cell voltage-clamp experiments were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to test the hypothesis that the differences in the amplitude of transient outward current (Ito) contribute to the difference in action potential configuration between endocardial and epicardial myocytes. In the control state, action potentials recorded from epicardial cells demonstrated a prominent notch between phases 1 and 2, and membrane current recordings displayed a prominent Ito, whereas in endocardial cells the notch in action potentials and Ito were small. External application of 4-aminopyridine (2 mM) reduced the amplitudes of notch and Ito in epicardial cells but not in endocardial cells. After application of 4-aminopyridine (2 mM) and caffeine (5 mM), the notch and Ito were abolished completely in both endocardial and epicardial cells. The first component of Ito (Ito1) was present in all epicardial cells studied (n = 20); it was absent in 12 of the 20 endocardial cells, and a small Ito1 was present in the remaining eight endocardial cells. The mean amplitude of Ito1 was significantly greater in epicardial than in endocardial cells. At a test voltage of +80 mV, the amplitude of Ito1 was 102.0 +/- 47.7 pA/pF in epicardial cells and 3.3 +/- 3.3 pA/pF in endocardial cells (p less than 0.01). The second component of Ito (Ito2) was present in all endocardial (n = 30) and epicardial (n = 30) cells studied. The amplitude of Ito2 was significantly greater in epicardial than in endocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Fitting membrane resistance along with action potential shape in cardiac myocytes improves convergence: application of a multi-objective parallel genetic algorithm.

PubMed

Kaur, Jaspreet; Nygren, Anders; Vigmond, Edward J

2014-01-01

Fitting parameter sets of non-linear equations in cardiac single cell ionic models to reproduce experimental behavior is a time consuming process. The standard procedure is to adjust maximum channel conductances in ionic models to reproduce action potentials (APs) recorded in isolated cells. However, vastly different sets of parameters can produce similar APs. Furthermore, even with an excellent AP match in case of single cell, tissue behaviour may be very different. We hypothesize that this uncertainty can be reduced by additionally fitting membrane resistance (Rm). To investigate the importance of Rm, we developed a genetic algorithm approach which incorporated Rm data calculated at a few points in the cycle, in addition to AP morphology. Performance was compared to a genetic algorithm using only AP morphology data. The optimal parameter sets and goodness of fit as computed by the different methods were compared. First, we fit an ionic model to itself, starting from a random parameter set. Next, we fit the AP of one ionic model to that of another. Finally, we fit an ionic model to experimentally recorded rabbit action potentials. Adding the extra objective (Rm, at a few voltages) to the AP fit, lead to much better convergence. Typically, a smaller MSE (mean square error, defined as the average of the squared error between the target AP and AP that is to be fitted) was achieved in one fifth of the number of generations compared to using only AP data. Importantly, the variability in fit parameters was also greatly reduced, with many parameters showing an order of magnitude decrease in variability. Adding Rm to the objective function improves the robustness of fitting, better preserving tissue level behavior, and should be incorporated.

Post-evaluation of the neurophaties treatment post-trauma with therapeutic laser. Model in sciatic nerve of frog

NASA Astrophysics Data System (ADS)

Escobar, Antonio S.; Ocampo, Arcelia F. M.; Hernández, María G. H.; Jasso, José L. C.; Lira, Maricela O. F.; Flores, Mariana A.; Balderrama, Vicente L.

2010-05-01

The purpose of this study was to evaluate the compound nerve action potential amplitude and latency measured to determine the degree of myelination and the number of fibers stimulated in a model of stimulated frog sciatic nerve laser at 810 nm as perioperative treatment after injury. It used 30 bullfrogs (Rana catesbeiana) to obtain 60 sciatic nerves forming four groups, groups 1 and 2 worked with nerves in vitro, were dissected in humid chambers for placing isolated organ, was recorded on compound nerve action potential, the second group laser was applied at 24, 48, 72, 96 and 120 hours and at the same time were placed in 10% formalin. Groups 3 and 4 are worked in vivo localizing the nerve and causing damage through compression, occurred over the compound nerve action potential to assess the degree of myelination and the number of fibers stimulated, the group 4 was applied to 810 nm laser (500 Hz, 10 J, 200 mW) after injury, after 48 hours, three frogs were sacrificed by introducing the nerves in 10% formalin. The latency recorded by stimulating the sciatic nerve of frog to 0.5 mA and 100 ms in groups 1 and 2 show significant differences (p<0.001 and p<000) as in the amplitude (p<000 and p<000). Groups 3 and 4, which was stimulated at 100 mA and 100 ms latency showed no statistically significant difference (p>000), as to the extent, if any statistically significant difference. (p<0.001 and p<0.000). The laser produces a favorable response in the treatment of paresthesia (post-traumatic neuropathy).

Mechanisms and distribution of ion channels in retinal ganglion cells: using temperature as an independent variable.

PubMed

Fohlmeister, Jürgen F; Cohen, Ethan D; Newman, Eric A

2010-03-01

Trains of action potentials of rat and cat retinal ganglion cells (RGCs) were recorded intracellularly across a temperature range of 7-37 degrees C. Phase plots of the experimental impulse trains were precision fit using multicompartment simulations of anatomically reconstructed rat and cat RGCs. Action potential excitation was simulated with a "Five-channel model" [Na, K(delayed rectifier), Ca, K(A), and K(Ca-activated) channels] and the nonspace-clamped condition of the whole cell recording was exploited to determine the channels' distribution on the dendrites, soma, and proximal axon. At each temperature, optimal phase-plot fits for RGCs occurred with the same unique channel distribution. The "waveform" of the electrotonic current was found to be temperature dependent, which reflected the shape changes in the experimental action potentials and confirmed the channel distributions. The distributions are cell-type specific and adequate for soma and dendritic excitation with a safety margin. The highest Na-channel density was found on an axonal segment some 50-130 microm distal to the soma, as determined from the temperature-dependent "initial segment-somadendritic (IS-SD) break." The voltage dependence of the gating rate constants remains invariant between 7 and 23 degrees C and between 30 and 37 degrees C, but undergoes a transition between 23 and 30 degrees C. Both gating-kinetic and ion-permeability Q10s remain virtually constant between 23 and 37 degrees C (kinetic Q10s = 1.9-1.95; permeability Q10s = 1.49-1.64). The Q10s systematically increase for T <23 degrees C (kinetic Q10 = 8 at T = 8 degrees C). The Na channels were consistently "sleepy" (non-Arrhenius) for T <8 degrees C, with a loss of spiking for T <7 degrees C.

Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate

PubMed Central

Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O’Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

2014-01-01

Background Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Methods and Results Activation recovery intervals (ARI) measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady state pacing while subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Haemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (p=0.001). APD decreased during the stressful parts of the film clip, eg for global RV ARI at end of film clip 193.8ms (SD 14) vs 198.0ms (SD13) during the matched breathing control (end film LV 199.8ms (SD16) vs control 201.6ms (SD15), p=0.004. Respiration rate increased during the stressful part of the film clip (by 2 breaths/minute), and was well matched in the respective control period without any haemodynamic or ARI changes. Conclusions Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular action potential duration in conscious humans. The effect of mental challenge on APD was not secondary to emotionally-induced altered respiration or heart rate. PMID:24833641

32 CFR 723.7 - Action by the Secretary.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 false Action by the Secretary. 723.7 Section 723.7... NAVAL RECORDS § 723.7 Action by the Secretary. (a) General. The record of proceedings, except in cases... hearing, will be forwarded to the Secretary who will direct such action as he or she determines to be...

Inventory Data Package for Hanford Assessments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kincaid, Charles T.; Eslinger, Paul W.; Aaberg, Rosanne L.

2006-06-01

This document presents the basis for a compilation of inventory for radioactive contaminants of interest by year for all potentially impactive waste sites on the Hanford Site for which inventory data exist in records or could be reasonably estimated. This document also includes discussions of the historical, current, and reasonably foreseeable (1944 to 2070) future radioactive waste and waste sites; the inventories of radionuclides that may have a potential for environmental impacts; a description of the method(s) for estimating inventories where records are inadequate; a description of the screening method(s) used to select those sites and contaminants that might makemore » a substantial contribution to impacts; a listing of the remedial actions and their completion dates for waste sites; and tables showing the best estimate inventories available for Hanford assessments.« less

Predicting human activities in sequences of actions in RGB-D videos

NASA Astrophysics Data System (ADS)

Jardim, David; Nunes, Luís.; Dias, Miguel

2017-03-01

In our daily activities we perform prediction or anticipation when interacting with other humans or with objects. Prediction of human activity made by computers has several potential applications: surveillance systems, human computer interfaces, sports video analysis, human-robot-collaboration, games and health-care. We propose a system capable of recognizing and predicting human actions using supervised classifiers trained with automatically labeled data evaluated in our human activity RGB-D dataset (recorded with a Kinect sensor) and using only the position of the main skeleton joints to extract features. Using conditional random fields (CRFs) to model the sequential nature of actions in a sequence has been used before, but where other approaches try to predict an outcome or anticipate ahead in time (seconds), we try to predict what will be the next action of a subject. Our results show an activity prediction accuracy of 89.9% using an automatically labeled dataset.

Click- and chirp-evoked human compound action potentials

PubMed Central

Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

2010-01-01

In the experiments reported here, the amplitude and the latency of human compound action potentials (CAPs) evoked from a chirp stimulus are compared to those evoked from a traditional click stimulus. The chirp stimulus was created with a frequency sweep to compensate for basilar membrane traveling wave delay using the O-Chirp equations from Fobel and Dau [(2004). J. Acoust. Soc. Am. 116, 2213–2222] derived from otoacoustic emission data. Human cochlear traveling wave delay estimates were obtained from derived compound band action potentials provided by Eggermont [(1979). J. Acoust. Soc. Am. 65, 463–470]. CAPs were recorded from an electrode placed on the tympanic membrane (TM), and the acoustic signals were monitored with a probe tube microphone attached to the TM electrode. Results showed that the amplitude and latency of chirp-evoked N1 of the CAP differed from click-evoked CAPs in several regards. For the chirp-evoked CAP, the N1 amplitude was significantly larger than the click-evoked N1s. The latency-intensity function was significantly shallower for chirp-evoked CAPs as compared to click-evoked CAPs. This suggests that auditory nerve fibers respond with more unison to a chirp stimulus than to a click stimulus. PMID:21117748

Transient extracellular application of gold nanostars increases hippocampal neuronal activity.

PubMed

Salinas, Kirstie; Kereselidze, Zurab; DeLuna, Frank; Peralta, Xomalin G; Santamaria, Fidel

2014-08-20

With the increased use of nanoparticles in biomedical applications there is a growing need to understand the effects that nanoparticles may have on cell function. Identifying these effects and understanding the mechanism through which nanoparticles interfere with the normal functioning of a cell is necessary for any therapeutic or diagnostic application. The aim of this study is to evaluate if gold nanoparticles can affect the normal function of neurons, namely their activity and coding properties. We synthesized star shaped gold nanoparticles of 180 nm average size. We applied the nanoparticles to acute mouse hippocampal slices while recording the action potentials from single neurons in the CA3 region. Our results show that CA3 hippocampal neurons increase their firing rate by 17% after the application of gold nanostars. The increase in excitability lasted for as much as 50 minutes after a transient 5 min application of the nanoparticles. Further analyses of the action potential shape and computational modeling suggest that nanoparticles block potassium channels responsible for the repolarization of the action potentials, thus allowing the cell to increase its firing rate. Our results show that gold nanoparticles can affect the coding properties of neurons by modifying their excitability.

Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

PubMed

Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

2005-04-01

This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

Rat electropharmacograms of the flavonoids rutin and quercetin in comparison to those of moclobemide and clinically used reference drugs suggest antidepressive and/or neuroprotective action.

PubMed

Dimpfel, Wilfried

2009-04-01

In order to be able to test single constituents of herbal plant extracts with respect to possible clinical usefulness, the model of local field potential analysis leading to the so-called electropharmacogram has been successfully used in rats to classify the effects of theanine and theogallin in the past. The present investigation aims at the prediction of efficacy and possible mechanisms of action of rutin and quercetin. Adult rats (day-night converted) were instrumented with four bipolar concentric electrodes into the frontal cortex, hippocampus, striatum and reticular formation. Field potentials were recorded during a pre-drug reference period of 45 min followed by oral administration of the particular test compound and 4h recording thereafter. Data were transmitted wirelessly to the computer for spectral frequency analysis. Rutin (5-80 mg/kg) as well as quercetin (5-40 mg/kg orally) produced similar electropharmacograms with dose dependent decreases of spectral alpha2 and beta1 frequencies within all brain areas. Peak effects were reached 4h after administration. The pattern of changes approached that obtained after 2.5mg/kg of moclobemide during the first hour as revealed by discriminant analysis in comparison to a large matrix of other drugs with known clinical indications. Data suggest antidepressant capabilities for rutin and quercetin with inhibition of monoamino oxidase at least as part of the mechanism of action. Both compounds should be tested clinically in patients with symptoms of depression.

Neural hijacking: action of high-frequency electrical stimulation on cortical circuits.

PubMed

Cheney, P D; Griffin, D M; Van Acker, G M

2013-10-01

Electrical stimulation of the brain was one of the first experimental methods applied to understanding brain organization and function and it continues as a highly useful method both in research and clinical applications. Intracortical microstimulation (ICMS) involves applying electrical stimuli through a microelectrode suitable for recording the action potentials of single neurons. ICMS can be categorized into single-pulse stimulation; high-frequency, short-duration stimulation; and high-frequency, long-duration stimulation. For clinical and experimental reasons, considerable interest focuses on the mechanism of neural activation by electrical stimuli. In this article, we discuss recent results suggesting that action potentials evoked in cortical neurons by high-frequency electrical stimulation do not sum with the natural, behaviorally related background activity; rather, high-frequency stimulation eliminates and replaces natural activity. We refer to this as neural hijacking. We propose that a major component of the mechanism underlying neural hijacking is excitation of axons by ICMS and elimination of natural spikes by antidromic collision with stimulus-driven spikes evoked at high frequency. Evidence also supports neural hijacking as an important mechanism underlying the action of deep brain stimulation in the subthalamic nucleus and its therapeutic effect in treating Parkinson's disease.

Estimating the duration of intracellular action potentials in muscle fibres from single-fibre extracellular potentials.

PubMed

Rodríguez, Javier; Navallas, Javier; Gila, Luis; Dimitrova, Nonna Alexandrovna; Malanda, Armando

2011-04-30

In situ recording of the intracellular action potential (IAP) of human muscle fibres is not yet possible, and consequently, knowledge concerning certain IAP characteristics is still limited. According to the core-conductor theory, close to a fibre, a single fibre action potential (SFAP) can be assumed to be proportional to the IAP second derivative. Thus, we might expect to be able to derive some characteristics of the IAP, such as the duration of its spike, from the SFAP waveform. However, SFAP properties not only depend on the IAP shape but also on the fibre-to-electrode (radial) distance and other physiological properties of the fibre. In this paper we, first, propose an SFAP parameter (the negative phase duration, NPD) appropriate for estimating the IAP spike duration and, second, show that this parameter is largely independent of changes in radial distance and muscle fibre propagation velocity. Estimation of the IAP spike duration from a direct measurement taken from the SFAP waveform provides a possible way to enhance the accuracy of SFAP models. Because IAP spike duration is known to be sensitive to the effects of fatigue and calcium accumulation, the proposed SFAP parameter, the NPD, has potential value in electrodiagnosis and as an indicator of IAP profile changes due to peripheral fatigue. Copyright © 2011 Elsevier B.V. All rights reserved.

40 CFR 63.4931 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., measurement, maintenance, corrective action, report, or record. (c) You must keep each record on-site for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or...

40 CFR 63.4131 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., measurement, maintenance, corrective action, report, or record. (c) You must keep each record on site for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or...

40 CFR 63.4731 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., measurement, maintenance, corrective action, report, or record. (c) You must keep each record on-site for at least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or...

40 CFR 63.7753 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record. (c..., maintenance, corrective action, report, or record according to the requirements in § 63.10(b)(1). You can keep...

Short- and medium-term plasticity associated with augmenting responses in cortical slabs and spindles in intact cortex of cats in vivo

PubMed Central

Timofeev, Igor; Grenier, François; Bazhenov, Maxim; Houweling, Arthur R; Sejnowski, Terrence J; Steriade, Mircea

2002-01-01

Plastic changes in the synaptic responsiveness of neocortical neurones, which occur after rhythmic stimuli within the frequency range of sleep spindles (10 Hz), were investigated in isolated neocortical slabs and intact cortex of anaesthetized cats by means of single, dual and triple simultaneous intracellular recordings in conjunction with recordings of local field potential responses. In isolated cortical slabs (10 mm long, 6 mm wide and 4–5 mm deep), augmenting responses to pulse-trains at 10 Hz (responses with growing amplitudes from the second stimulus in a train) were elicited only by relatively high-intensity stimuli. At low intensities, responses were decremental. The largest augmenting responses were evoked in neurones located close to the stimulation site. Quantitative analyses of the number of action potentials and the amplitude and area of depolarization during augmenting responses in a population of neurones recorded from slabs showed that the most dramatic increases in the number of spikes with successive stimuli, and the greatest increase in depolarization amplitude, were found in conventional fast-spiking (FS) neurones. The largest increase in the area of depolarization was found in regular-spiking (RS) neurones. Dual intracellular recordings from a pair of FS and RS neurones in the slab revealed more action potentials in the FS neurone during augmenting responses and a significant increase in the depolarization area of the RS neurone that was dependent on the firing of the FS neurone. Self-sustained seizures could occur in the slab after rhythmic stimuli at 10 Hz. In the intact cortex, repeated sequences of stimuli generating augmenting responses or spontaneous spindles could induce an increased synaptic responsiveness to single stimuli, which lasted for several minutes. A similar time course of increased responsiveness was obtained with induction of cellular plasticity. These data suggest that augmenting responses elicited by stimulation, as well as spontaneously occurring spindles, may induce short- and medium-term plasticity of neuronal responses. PMID:12122155

Large-scale electrophysiology: acquisition, compression, encryption, and storage of big data.

PubMed

Brinkmann, Benjamin H; Bower, Mark R; Stengel, Keith A; Worrell, Gregory A; Stead, Matt

2009-05-30

The use of large-scale electrophysiology to obtain high spatiotemporal resolution brain recordings (>100 channels) capable of probing the range of neural activity from local field potential oscillations to single-neuron action potentials presents new challenges for data acquisition, storage, and analysis. Our group is currently performing continuous, long-term electrophysiological recordings in human subjects undergoing evaluation for epilepsy surgery using hybrid intracranial electrodes composed of up to 320 micro- and clinical macroelectrode arrays. DC-capable amplifiers, sampling at 32kHz per channel with 18-bits of A/D resolution are capable of resolving extracellular voltages spanning single-neuron action potentials, high frequency oscillations, and high amplitude ultra-slow activity, but this approach generates 3 terabytes of data per day (at 4 bytes per sample) using current data formats. Data compression can provide several practical benefits, but only if data can be compressed and appended to files in real-time in a format that allows random access to data segments of varying size. Here we describe a state-of-the-art, scalable, electrophysiology platform designed for acquisition, compression, encryption, and storage of large-scale data. Data are stored in a file format that incorporates lossless data compression using range-encoded differences, a 32-bit cyclically redundant checksum to ensure data integrity, and 128-bit encryption for protection of patient information.

Large-scale Electrophysiology: Acquisition, Compression, Encryption, and Storage of Big Data

PubMed Central

Brinkmann, Benjamin H.; Bower, Mark R.; Stengel, Keith A.; Worrell, Gregory A.; Stead, Matt

2009-01-01

The use of large-scale electrophysiology to obtain high spatiotemporal resolution brain recordings (>100 channels) capable of probing the range of neural activity from local field potential oscillations to single neuron action potentials presents new challenges for data acquisition, storage, and analysis. Our group is currently performing continuous, long-term electrophysiological recordings in human subjects undergoing evaluation for epilepsy surgery using hybrid intracranial electrodes composed of up to 320 micro- and clinical macroelectrode arrays. DC-capable amplifiers, sampling at 32 kHz per channel with 18-bits of A/D resolution are capable of resolving extracellular voltages spanning single neuron action potentials, high frequency oscillations, and high amplitude ultraslow activity, but this approach generates 3 terabytes of data per day (at 4 bytes per sample) using current data formats. Data compression can provide several practical benefits, but only if data can be compressed and appended to files in real-time in a format that allows random access to data segments of varying size. Here we describe a state-of-the-art, scalable, electrophysiology platform designed for acquisition, compression, encryption, and storage of large-scale data. Data are stored in a file format that incorporates lossless data compression using range encoded differences, a 32-bit cyclically redundant checksum to ensure data integrity, and 128-bit encryption for protection of patient information. PMID:19427545

Factors affecting electronic health record adoption in long-term care facilities.

PubMed

Cherry, Barbara; Carter, Michael; Owen, Donna; Lockhart, Carol

2008-01-01

Electronic health records (EHRs) hold the potential to significantly improve the quality of care in long-term care (LTC) facilities, yet limited research has been done on how facilities decide to adopt these records. This study was conducted to identify factors that hinder and facilitate EHR adoption in LTC facilities. Study participants were LTC nurses, administrators, and corporate executives. Primary barriers identified were costs, the need for training, and the culture change required to embrace technology. Primary facilitators were training programs, well-defined implementation plans, government assistance with implementation costs, evidence that EHRs will improve care outcomes, and support from state regulatory agencies. These results offer a framework of action for policy makers, LTC Leaders, and researchers.

Glycogen synthase kinase 3 beta alters anxiety-, depression-, and addiction-related behaviors and neuronal activity in the nucleus accumbens shell

PubMed Central

Crofton, Elizabeth J.; Nenov, Miroslav N.; Zhang, Yafang; Scala, Federico; Page, Sean A.; McCue, David L.; Li, Dingge; Hommel, Jonathan D.; Laezza, Fernanda; Green, Thomas A.

2017-01-01

Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats. GSK3beta knockdown reduced anxiety-like behavior while increasing depression-like behavior and cocaine self-administration. Correlative electrophysiological recordings in acute brain slices were used to assess the effect of AAV-shGSK3beta on spontaneous firing and intrinsic excitability of tonically active interneurons (TANs), cells required for input and output signal integration in the NAcSh and for processing reward-related behaviors. Loose-patch recordings showed that TANs transduced by AAV-shGSK3beta exhibited reduction in tonic firing and increased spike half width. When assessed by whole-cell patch clamp recordings these changes were mirrored by reduction in action potential firing and accompanied by decreased hyperpolarization-induced depolarizing sag potentials, increased action potential current threshold, and decreased maximum rise time. These results suggest that silencing of GSK3beta in the NAcSh increases depression- and addiction-related behavior, possibly by decreasing intrinsic excitability of TANs. However, this study does not rule out contributions from other neuronal sub-types. PMID:28126496

Microprobe array with low impedance electrodes and highly flexible polyimide cables for acute neural recording.

PubMed

Kisban, S; Herwik, S; Seidl, K; Rubehn, B; Jezzini, A; Umiltà, M A; Fogassi, L; Stieglitz, T; Paul, O; Ruther, P

2007-01-01

This paper reports on a novel type of silicon-based microprobes with linear, two and three dimensional (3D) distribution of their recording sites. The microprobes comprise either single shafts, combs with multiple shafts or 3D arrays combining two combs with 9, 36 or 72 recording sites, respectively. The electrical interconnection of the probes is achieved through highly flexible polyimide ribbon cables attached using the MicroFlex Technology which allows a connection part of small lateral dimensions. For an improved handling, probes can be secured by a protecting canula. Low-impedance electrodes are achieved by the deposition of platinum black. First in vivo experiments proved the capability to record single action potentials in the motor cortex from electrodes close to the tip as well as body electrodes along the shaft.

Workflow in interventional radiology: nerve blocks and facet blocks

NASA Astrophysics Data System (ADS)

Siddoway, Donald; Ingeholm, Mary Lou; Burgert, Oliver; Neumuth, Thomas; Watson, Vance; Cleary, Kevin

2006-03-01

Workflow analysis has the potential to dramatically improve the efficiency and clinical outcomes of medical procedures. In this study, we recorded the workflow for nerve block and facet block procedures in the interventional radiology suite at Georgetown University Hospital in Washington, DC, USA. We employed a custom client/server software architecture developed by the Innovation Center for Computer Assisted Surgery (ICCAS) at the University of Leipzig, Germany. This software runs in an internet browser, and allows the user to record the actions taken by the physician during a procedure. The data recorded during the procedure is stored as an XML document, which can then be further processed. We have successfully gathered data on a number if cases using a tablet PC, and these preliminary results show the feasibility of using this software in an interventional radiology setting. We are currently accruing additional cases and when more data has been collected we will analyze the workflow of these procedures to look for inefficiencies and potential improvements.

Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

PubMed Central

Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry

2015-01-01

The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca2+-activated K+ channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. SIGNIFICANCE STATEMENT Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main compartments: dendritic, somatic, and axonal. How the neurons receive information, process it, and pass on new information depends upon how these three compartments operate. While it has long been assumed that axons are simply for conducting information from the cell body to the synapses, here we demonstrate that the axons of different types of interneurons, the inhibitory cells, possess differing electrophysiological properties. This result implies that differing types of interneurons perform different tasks in the cortex, not only through their anatomical connections, but also through how their axons operate. PMID:26609152

Big data from electronic health records for early and late translational cardiovascular research: challenges and potential.

PubMed

Hemingway, Harry; Asselbergs, Folkert W; Danesh, John; Dobson, Richard; Maniadakis, Nikolaos; Maggioni, Aldo; van Thiel, Ghislaine J M; Cronin, Maureen; Brobert, Gunnar; Vardas, Panos; Anker, Stefan D; Grobbee, Diederick E; Denaxas, Spiros

2018-04-21

Cohorts of millions of people's health records, whole genome sequencing, imaging, sensor, societal and publicly available data present a rapidly expanding digital trace of health. We aimed to critically review, for the first time, the challenges and potential of big data across early and late stages of translational cardiovascular disease research. We sought exemplars based on literature reviews and expertise across the BigData@Heart Consortium. We identified formidable challenges including: data quality, knowing what data exist, the legal and ethical framework for their use, data sharing, building and maintaining public trust, developing standards for defining disease, developing tools for scalable, replicable science and equipping the clinical and scientific work force with new inter-disciplinary skills. Opportunities claimed for big health record data include: richer profiles of health and disease from birth to death and from the molecular to the societal scale; accelerated understanding of disease causation and progression, discovery of new mechanisms and treatment-relevant disease sub-phenotypes, understanding health and diseases in whole populations and whole health systems and returning actionable feedback loops to improve (and potentially disrupt) existing models of research and care, with greater efficiency. In early translational research we identified exemplars including: discovery of fundamental biological processes e.g. linking exome sequences to lifelong electronic health records (EHR) (e.g. human knockout experiments); drug development: genomic approaches to drug target validation; precision medicine: e.g. DNA integrated into hospital EHR for pre-emptive pharmacogenomics. In late translational research we identified exemplars including: learning health systems with outcome trials integrated into clinical care; citizen driven health with 24/7 multi-parameter patient monitoring to improve outcomes and population-based linkages of multiple EHR sources for higher resolution clinical epidemiology and public health. High volumes of inherently diverse ('big') EHR data are beginning to disrupt the nature of cardiovascular research and care. Such big data have the potential to improve our understanding of disease causation and classification relevant for early translation and to contribute actionable analytics to improve health and healthcare.

Robust spike classification based on frequency domain neural waveform features.

PubMed

Yang, Chenhui; Yuan, Yuan; Si, Jennie

2013-12-01

We introduce a new spike classification algorithm based on frequency domain features of the spike snippets. The goal for the algorithm is to provide high classification accuracy, low false misclassification, ease of implementation, robustness to signal degradation, and objectivity in classification outcomes. In this paper, we propose a spike classification algorithm based on frequency domain features (CFDF). It makes use of frequency domain contents of the recorded neural waveforms for spike classification. The self-organizing map (SOM) is used as a tool to determine the cluster number intuitively and directly by viewing the SOM output map. After that, spike classification can be easily performed using clustering algorithms such as the k-Means. In conjunction with our previously developed multiscale correlation of wavelet coefficient (MCWC) spike detection algorithm, we show that the MCWC and CFDF detection and classification system is robust when tested on several sets of artificial and real neural waveforms. The CFDF is comparable to or outperforms some popular automatic spike classification algorithms with artificial and real neural data. The detection and classification of neural action potentials or neural spikes is an important step in single-unit-based neuroscientific studies and applications. After the detection of neural snippets potentially containing neural spikes, a robust classification algorithm is applied for the analysis of the snippets to (1) extract similar waveforms into one class for them to be considered coming from one unit, and to (2) remove noise snippets if they do not contain any features of an action potential. Usually, a snippet is a small 2 or 3 ms segment of the recorded waveform, and differences in neural action potentials can be subtle from one unit to another. Therefore, a robust, high performance classification system like the CFDF is necessary. In addition, the proposed algorithm does not require any assumptions on statistical properties of the noise and proves to be robust under noise contamination.

A Fiber-Based Ratiometric Optical Cardiac Mapping Channel Using a Diffraction Grating and Split Detector

PubMed Central

Brown, Ninita H.; Dobrovolny, Hana M.; Gauthier, Daniel J.; Wolf, Patrick D.

2007-01-01

Optical fiber-based mapping systems are used to record the cardiac action potential (AP) throughout the myocardium. The optical AP contains a contraction-induced motion artifact (MA), which makes it difficult to accurately measure the action potential duration (APD). MA is removed by preventing contraction with electrical-mechanical uncoupling drugs, such as 2,3-butanedione monoxime (BDM). We designed a novel fiber-based ratiometric optical channel using a blue light emitting diode, a diffraction grating, and a split photodetector that can accurately measure the cardiac AP without the need for BDM. The channel was designed based on simulations using the optical design software ZEMAX. The channel has an electrical bandwidth of 150 Hz and an root mean-square dark noise of 742 μV. The channel successfully recorded the cardiac AP from the wall of five rabbit heart preparations without the use of BDM. After 20-point median filtering, the mean signal/noise ratio was 25.3 V/V. The APD measured from the base of a rabbit heart was 134 ± 8.4 ms, compared to 137.6 ± 3.3 ms from simultaneous microelectrode recordings. This difference was not statistically significant (p-value = 0.3). The quantity of MA removed was also measured using the motion ratio. The reduction in MA was significant (p-value = 0.0001). This fiber-based system is the first of its kind to enable optical APD measurements in the beating heart wall without the use of BDM. PMID:17416627

The spike generator in the labellar taste receptors of the blowfly is differently affected by 4-aminopyridine and 5-hydroxytryptamine.

PubMed

Sollai, Giorgia; Solari, Paolo; Corda, Valentina; Masala, Carla; Crnjar, Roberto

2012-12-01

In taste chemoreception of invertebrates the interaction of taste stimuli with specific membrane receptors and/or ion channels located in the apical membrane of taste receptor cells results in the generation of a receptor potential which, in turn, activates the 'encoder' region to produce action potentials which propagate to the CNS. This study investigates, in the labellar chemosensilla of the blowfly, Protophormia terraenovae, the voltage-gated K(+) currents involved in the action potential repolarization and repetitive firing of the neurons by way of the K(v) channel inhibitors, 4-aminopyridine and 5-hydroxytryptamine. The receptor potential and the spike activity were simultaneously recorded from the 'salt', 'sugar' and 'deterrent' cells, by means of the extracellular side-wall technique, in response to 150 mM NaCl, 100 mM sucrose and 1 mM quinine HCl, before, 0÷10 min after apical administration of 4-AP (0.01-10 mM) or 5-HT (0.1-100 mM). The results show that the receptor potential in all three cells is neither affected by 4-AP nor by 5-HT. Instead, spike activity is significantly decreased, by way of blocking different K(v) channel types: an inactivating A-type K(+) current (KA) modulating repetitive firing of the cells and responsible for the after hyperpolarization, and a sustained K(+) current that resembles the delayed rectifier (DKR) and contributes to action potential repolarization. Copyright © 2012 Elsevier Ltd. All rights reserved.

To what extent do clinical notes by general practitioners reflect actual medical performance? A study using simulated patients.

PubMed Central

Rethans, J J; Martin, E; Metsemakers, J

1994-01-01

BACKGROUND. Review of clinical notes is used extensively as an indirect method of assessing doctors' performance. However, to be acceptable it must be valid. AIM. This study set out to examine the extent to which clinical notes in medical records of general practice consultations reflected doctors' actual performance during consultations. METHOD. Thirty nine general practitioners in the Netherlands were consulted by four simulated patients who were indistinguishable from real patients and who reported on the consultations. The complaints presented by the simulated patients were tension headache, acute diarrhoea and pain in the shoulder, and one presented for a check up for non-insulin dependent diabetes. Later, the doctors forwarded their medical records of these patients to the researchers. Content of consultations was measured against accepted standards for general practice and then compared with content of clinical notes. An index, or content score, was calculated as the measure of agreement between actions which had actually been recorded and actions which could have been recorded in the clinical notes. A high content score reflected a consultation which had been recorded well in the medical record. The correlation between number of actions across the four complaints recorded in the clinical notes and number of actions taken during the consultations was also calculated. RESULTS. The mean content score (interquartile range) for the four types of complaint was 0.32 (0.27-0.37), indicating that of all actions undertaken, only 32% had been recorded. However, mean content scores for the categories 'medication and therapy' and 'laboratory examination' were much higher than for the categories 'history' and 'guidance and advice' (0.68 and 0.64, respectively versus 0.29 and 0.22, respectively). The correlation between number of actions across the four complaints recorded in the clinical notes and number of actions taken during the consultations was 0.54 (P < 0.05). CONCLUSION. The use of clinical notes to audit doctors' performance in Dutch general practice is invalid. However, the use of clinical notes to rank doctors according to those who perform many or a few actions in a consultation may be justified. PMID:8185988

The Summating Potential Is a Reliable Marker of Electrode Position in Electrocochleography: Cochlear Implant as a Theragnostic Probe.

PubMed

Helmstaedter, Victor; Lenarz, Thomas; Erfurt, Peter; Kral, Andrej; Baumhoff, Peter

2017-12-14

For the increasing number of cochlear implantations in subjects with residual hearing, hearing preservation, and thus the prevention of implantation trauma, is crucial. A method for monitoring the intracochlear position of a cochlear implant (CI) and early indication of imminent cochlear trauma would help to assist the surgeon to achieve this goal. The aim of this study was to evaluate the reliability of the different electric components recorded by an intracochlear electrocochleography (ECochG) as markers for the cochleotopic position of a CI. The measurements were made directly from the CI, combining intrasurgical diagnostics with the therapeutical use of the CI, thus, turning the CI into a "theragnostic probe." Intracochlear ECochGs were measured in 10 Dunkin Hartley guinea pigs of either sex, with normal auditory brainstem response thresholds. All subjects were fully implanted (4 to 5 mm) with a custom six contact CI. The ECochG was recorded simultaneously from all six contacts with monopolar configuration (retroauricular reference electrode). The gross ECochG signal was filtered off-line to separate three of its main components: compound action potential, cochlear microphonic, and summating potential (SP). Additionally, five cochleae were harvested and histologically processed to access the spatial position of the CI contacts. Both ECochG data and histological reconstructions of the electrode position were fitted with the Greenwood function to verify the reliability of the deduced cochleotopic position of the CI. SPs could be used as suitable markers for the frequency position of the recording electrode with an accuracy of ±1/4 octave in the functioning cochlea, verified by histology. Cochlear microphonics showed a dependency on electrode position but were less reliable as positional markers. Compound action potentials were not suitable for CI position information but were sensitive to "cochlear health" (e.g., insertion trauma). SPs directly recorded from the contacts of a CI during surgery can be used to access the intracochlear frequency position of the CI. Using SP monitoring, implantation may be stopped before penetrating functioning cochlear regions. If the technique was similarly effective in humans, it could prevent implantation trauma and increase hearing preservation during CI surgery. Diagnostic hardware and software for recording biological signals with a CI without filter limitations might be a valuable add-on to the portfolios of CI manufacturers.

Deciphering the contribution of intrinsic and synaptic currents to the effects of transient synaptic inputs on human motor unit discharge

PubMed Central

Powers, Randall K.; Türker, Kemal S.

2010-01-01

The amplitude and time course of synaptic potentials in human motoneurons can be estimated in tonically discharging motor units by measuring stimulus-evoked changes in the rate and probability of motor unit action potentials. However, in spite of the fact that some of these techniques have been used for over thirty years, there is still no consensus on the best way to estimate the characteristics of synaptic potentials or on the accuracy of these estimates. In this review, we compare different techniques for estimating synaptic potentials from human motor unit discharge and also discuss relevant animal models in which estimated synaptic potentials can be compared to those directly measured from intracellular recordings. We also review the experimental evidence on how synaptic noise and intrinsic motoneuron properties influence their responses to synaptic inputs. Finally, we consider to what extent recordings of single motor unit discharge in humans can be used to distinguish the contribution of changes in synaptic inputs versus changes in intrinsic motoneuron properties to altered motoneuron responses following CNS injury. PMID:20427230

Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

NASA Astrophysics Data System (ADS)

Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

2016-08-01

A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

Heterogeneous memory in restitution of action potential duration in pig ventricles.

PubMed

Jing, Linyuan; Chourasia, Sonam; Patwardhan, Abhijit

2010-01-01

Restitution of action potential duration and memory importantly affect electrical stability in ventricles. Studies have reported heterogeneous restitution among different regions of the ventricles. However, existence of heterogeneity in memory is not as well investigated. Transmembrane potentials were recorded in endocardial and epicardial tissues from both ventricles of farm pigs. Pacing protocols with sinusoidally changing diastolic intervals were used to reveal hysteresis in restitution, from which quantitative measures of memory were calculated. Larger measures of hysteresis were observed in the endocardium than the epicardium (P < .05): loop thickness (in milliseconds), 26.9 vs 16.2; overall tilt, 0.376 vs 0.249; and loop area (in square milliseconds), 7288 vs 4146. Except for overall tilt, no significant differences in these measures were observed between ventricles. Heterogeneity in memory exists in pig ventricles. Because regions with the steepest restitution may also have the largest memory, our results suggest that heterogeneity in memory should also be factored in when predicting electrical stability. Copyright 2010 Elsevier Inc. All rights reserved.

An evaluation of the utility and limitations of counting motor unit action potentials in the surface electromyogram

NASA Astrophysics Data System (ADS)

Zhou, Ping; Zev Rymer, William

2004-12-01

The number of motor unit action potentials (MUAPs) appearing in the surface electromyogram (EMG) signal is directly related to motor unit recruitment and firing rates and therefore offers potentially valuable information about the level of activation of the motoneuron pool. In this paper, based on morphological features of the surface MUAPs, we try to estimate the number of MUAPs present in the surface EMG by counting the negative peaks in the signal. Several signal processing procedures are applied to the surface EMG to facilitate this peak counting process. The MUAP number estimation performance by this approach is first illustrated using the surface EMG simulations. Then, by evaluating the peak counting results from the EMG records detected by a very selective surface electrode, at different contraction levels of the first dorsal interosseous (FDI) muscles, the utility and limitations of such direct peak counts for MUAP number estimation in surface EMG are further explored.

Telemetric recordings of single neuron activity and visual scenes in monkeys walking in an open field.

PubMed

Lei, Yanlin; Sun, Ninglei; Wilson, Fraser A W; Wang, Xiusong; Chen, Nanhui; Yang, Jianzhen; Peng, Yanping; Wang, Jianhong; Tian, Shaohua; Wang, Maohua; Miao, Yingda; Zhu, Weina; Qi, Hua; Ma, Yuanye

2004-05-30

This paper describes a portable recording system and methods for obtaining chronic recordings of single units and tracking rhesus monkey behavior in an open field. The integrated system consists of four major components: (1) microelectrode assembly; (2) head-stage; (3) recording station; and (4) data storage station, the first three of which are carried by the monkey and weigh 800 g. Our system provides synchronized video and electrophysiological signals, which are transmitted by a wireless system to a distance of 50 m. Its major advantages are that neuronal recordings are made in freely moving monkeys, and well-separated action potentials with amplitude five times higher than the background noise are usually recorded and readily kept for many hours. Using this system, we were able to study "place cells" in non-human primate brains. The described methods provide a new way to examine correlations between single neuron activity and primate behaviors, and can also be used to study the cellular basis of social behaviors in non-human primates.

Corrective Action Investigation Plan for Corrective Action Unit 527: Horn Silver Mine, Nevada Test Site, Nevada: Revision 1 (Including Records of Technical Change No.1, 2, 3, and 4)

DOE Office of Scientific and Technical Information (OSTI.GOV)

U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office

This Corrective Action Investigation Plan contains the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 527, Horn Silver Mine, Nevada Test Site, Nevada, under the Federal Facility Agreement and Consent Order. Corrective Action Unit 527 consists of one Corrective Action Site (CAS): 26-20-01, Contaminated Waste Dump No.1. The site is located in an abandoned mine site in Area 26 (which is the most arid part of the NTS) approximately 65 miles northwest of Las Vegas. Historicalmore » documents may refer to this site as CAU 168, CWD-1, the Wingfield mine (or shaft), and the Wahmonie mine (or shaft). Historical documentation indicates that between 1959 and the 1970s, nonliquid classified material and unclassified waste was placed in the Horn Silver Mine's shaft. Some of the waste is known to be radioactive. Documentation indicates that the waste is present from 150 feet to the bottom of the mine (500 ft below ground surface). This CAU is being investigated because hazardous constituents migrating from materials and/or wastes disposed of in the Horn Silver Mine may pose a threat to human health and the environment as well as to assess the potential impacts associated with any potential releases from the waste. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Auditory steady-state evoked potentials vs. compound action potentials for the measurement of suppression tuning curves in the sedated dog puppy.

PubMed

Markessis, Emily; Poncelet, Luc; Colin, Cécile; Hoonhorst, Ingrid; Collet, Grégory; Deltenre, Paul; Moore, Brian C J

2010-06-01

Auditory steady-state evoked potential (ASSEP) tuning curves were compared to compound action potential (CAP) tuning curves, both measured at 2 Hz, using sedated beagle puppies. The effect of two types of masker (narrowband noise and sinusoidal) on the tuning curve parameters was assessed. Whatever the masker type, CAP tuning curve parameters were qualitatively and quantitatively similar to the ASSEP ones, with a similar inter-subject variability, but with a greater incidence of upward tip displacement. Whatever the procedure, sinusoidal maskers produced sharper tuning curves than narrow-band maskers. Although these differences are not likely to have significant implications for clinical work, from a fundamental point of view, their origin requires further investigations. The same amount of time was needed to record a CAP and an ASSEP 13-point tuning curve. The data further validate the ASSEP technique, which has the advantages of having a smaller tendency to produce upward tip shifts than the CAP technique. Moreover, being non invasive, ASSEP tuning curves can be easily repeated over time in the same subject for clinical and research purposes.

Scalable Electrophysiological Investigation of iPS Cell-Derived Cardiomyocytes Obtained by a Lentiviral Purification Strategy.

PubMed

Friedrichs, Stephanie; Malan, Daniela; Voss, Yvonne; Sasse, Philipp

2015-01-08

Disease-specific induced pluripotent stem (iPS) cells can be generated from patients and differentiated into functional cardiomyocytes for characterization of the disease and for drug screening. In order to obtain pure cardiomyocytes for automated electrophysiological investigation, we here report a novel non-clonal purification strategy by using lentiviral gene transfer of a puromycin resistance gene under the control of a cardiac-specific promoter. We have applied this method to our previous reported wild-type and long QT syndrome 3 (LQTS 3)-specific mouse iPS cells and obtained a pure cardiomyocyte population. These cells were investigated by action potential analysis with manual and automatic planar patch clamp technologies, as well as by recording extracellular field potentials using a microelectrode array system. Action potentials and field potentials showed the characteristic prolongation at low heart rates in LQTS 3-specific, but not in wild-type iPS cell-derived cardiomyocytes. Hence, LQTS 3-specific cardiomyocytes can be purified from iPS cells with a lentiviral strategy, maintain the hallmarks of the LQTS 3 disease and can be used for automated electrophysiological characterization and drug screening.

How action selection can be embodied: intracranial gamma band recording shows response competition during the Eriksen flankers test

PubMed Central

Caruana, Fausto; Uithol, Sebo; Cantalupo, Gaetano; Sartori, Ivana; Lo Russo, Giorgio; Avanzini, Pietro

2014-01-01

Recent findings in monkeys suggest that action selection is based on a competition between various action options that are automatically planned by the motor system. Here we discuss data from intracranial EEG recordings in human premotor cortex (PMC) during a bimanual version of the Eriksen flankers test that suggest that the same principles apply to human action decisions. Recording sites in the dorsal PMC show an early but undifferentiated activation, a delayed response that depends on the experimental conditions and, finally, a movement related activation during action execution. Additionally, we found that the medial part of the PMC show a significant increase in response for ipsilateral trials, suggesting a role in inhibiting the wrong response. The ventral PMC seems to be involved in action execution, rather than action selection. Together these findings suggest that the human PMC is part of a network that specifies, selects, and executes actions. PMID:25206328

Cerebellar interaction with the acoustic reflex.

PubMed

Jastreboff, P J

1981-01-01

The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.

Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias.

PubMed

Lu, H R; Hortigon-Vinagre, M P; Zamora, V; Kopljar, I; De Bondt, A; Gallacher, D J; Smith, G

2017-09-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T rise ) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I Ca -antagonists, I Kr -activator or ATP-sensitive K + channel (K ATP )-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free effective therapeutic plasma levels or effective concentrations by other studies. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. Copyright © 2017 Elsevier Inc. All rights reserved.

Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

PubMed

Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

2015-01-01

Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for studying evoked compound action potentials in neural regeneration studies.

Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials

PubMed Central

Potas, Jason Robert; de Castro, Newton Gonçalves; Maddess, Ted; de Souza, Marcio Nogueira

2015-01-01

Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for studying evoked compound action potentials in neural regeneration studies. PMID:26325291

33 CFR 52.64 - Final action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... OF MILITARY RECORDS OF THE COAST GUARD Judgment and Disposition § 52.64 Final action. (a) The Board.... 1552, as follows: (1) The Board may deny an application for the correction of military records. (2... for the correction of military records in any of the following categories: (i) An application to...

40 CFR 300.815 - Administrative record file for a remedial action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SUBSTANCES POLLUTION CONTINGENCY PLAN Administrative Record for Selection of Response Action § 300.815... investigation phase. At such time, the lead agency shall publish in a major local newspaper of general circulation a notice of the availability of the administrative record file. (b) The lead agency shall provide...

UNMEDULLATED FIBERS ORIGINATING IN DORSAL ROOT GANGLIA

PubMed Central

Gasser, Herbert S.

1950-01-01

The compound action potential of the unmedullated fibers arising from dorsal root ganglia, as recorded in cat skin nerves after conduction of simultaneously initiated impulses, shows among its components a temporal dispersion corresponding to velocities between 2.3 and 0.7 M.P.S. The maximum representation of the component velocities is at about 1.2 M.P.S. On both sides of the maximum the representation falls off irregularly, in such a way that groupings in the distribution produce in the action potential a configuration in which successive features appear always in the same positions at a given conduction distance. Through this demonstration of a characteristic configuration the system of the unmedullated fibers is brought into analogy with that of the medullated fibers. The unmedullated fibers originating in the dorsal root ganglia have distinctive physiological properties, among which is a large positive potential which reaches its maximum immediately after the spike and decrements to half relaxation in about 50 msec., at 37°C. The positive phases of the unit potentials in the compound action potential, owing to their duration, sum to a much greater extent than the temporally dispersed spikes; and, since they have sizes such that one equivalent to 25 per cent of the spike height would not be at the limit, in the summation process the major portion of the compound action potential is caused to be written at a potential level positive to the starting base line. The position of the spikes in the sequence can be seen in the analyses in Section III. The course of the activity in unit fibers is subject to variation in ways affecting the positive potential. Preliminary descriptions, based on orienting experiments, of how these variations are conditioned are given in Section I. Two of the findings are particularly noteworthy. One is the high sensitivity of the dimensions of the postspike positivity to temperature in the range of temperatures at which skin nerves may be expected to function, even when the environmental temperatures of an animal are moderate. The other is the high sensitivity to conditioning by previous activity. The positivity is first decreased, then replaced by a negative potential of similar duration. Reasons have been given why it is inadvisable at the present time to call the postspike potential an after-potential. A comparison has been made of the properties of the unmedullated fibers arising from dorsal root ganglia with those of fibers arising from sympathetic ganglia. The differences are so great that, in the interest of precision in designation, a division of the C group of fibers into two subgroups is indicated. It is suggested that the two subgroups be named respectively d.r.C and s.C. Measurements have been made of the diameters of the d.r.C fibers in a saphenous nerve stained with silver. Graphs showing the number of fibers at each diameter are presented in Section II. In Section III there are shown constructions, from histological data, of the action potential as it would appear, after 3 cm. of conduction, with the correlation between diameter and velocity in strict linearity. The degree of fit between the constructed and recorded potentials can be seen in Fig. 18. PMID:15428610

Development and modulation of intrinsic membrane properties control the temporal precision of auditory brain stem neurons.

PubMed

Franzen, Delwen L; Gleiss, Sarah A; Berger, Christina; Kümpfbeck, Franziska S; Ammer, Julian J; Felmy, Felix

2015-01-15

Passive and active membrane properties determine the voltage responses of neurons. Within the auditory brain stem, refinements in these intrinsic properties during late postnatal development usually generate short integration times and precise action-potential generation. This developmentally acquired temporal precision is crucial for auditory signal processing. How the interactions of these intrinsic properties develop in concert to enable auditory neurons to transfer information with high temporal precision has not yet been elucidated in detail. Here, we show how the developmental interaction of intrinsic membrane parameters generates high firing precision. We performed in vitro recordings from neurons of postnatal days 9-28 in the ventral nucleus of the lateral lemniscus of Mongolian gerbils, an auditory brain stem structure that converts excitatory to inhibitory information with high temporal precision. During this developmental period, the input resistance and capacitance decrease, and action potentials acquire faster kinetics and enhanced precision. Depending on the stimulation time course, the input resistance and capacitance contribute differentially to action-potential thresholds. The decrease in input resistance, however, is sufficient to explain the enhanced action-potential precision. Alterations in passive membrane properties also interact with a developmental change in potassium currents to generate the emergence of the mature firing pattern, characteristic of coincidence-detector neurons. Cholinergic receptor-mediated depolarizations further modulate this intrinsic excitability profile by eliciting changes in the threshold and firing pattern, irrespective of the developmental stage. Thus our findings reveal how intrinsic membrane properties interact developmentally to promote temporally precise information processing. Copyright © 2015 the American Physiological Society.

Prejunctional and postjunctional actions of heptanol and 18 beta-glycyrretinic acid in the rodent vas deferens.

PubMed

Rahman, Faisal; Manchanda, Rohit; Brain, Keith L

2009-06-15

Heptanol and 18 beta-glycyrrhetinic acid (18 beta GA) block gap junctions, but have other actions on transmitter release that have not been characterised. This study investigates the prejunctional and postjunctional effects of these compounds in guinea pig and mouse vas deferens using intracellular electrophysiological recording and confocal Ca(2+) imaging of sympathetic nerve terminals. In mice, heptanol (2 mM) reversibly decreased the amplitude of purinergic excitatory junction potentials (EJPs; 52+/-5%, P<0.05) while having little effect on spontaneous excitatory junction potentials (sEJPs). Heptanol (2 mM) reversibly abolished the nerve terminal Ca(2+) transient in 52% of terminals. 18 beta GA (10 microM) decreased the mean EJP amplitude, and increased input resistance in both mouse (137+/-17%, P<0.05) and guinea pig (354+/-50%, P<0.001) vas deferens indicating gap junction blockade. Further, 18 beta GA increased the sEJP frequency significantly in guinea pigs (by 71+/-25%, P<0.05) and in 5 out of 6 tissues in mice (19+/-3%, P<0.05). Moreover, 18 beta GA depolarised cells from both mice (11+/-1%, P<0.01) and guinea pigs (8+/-1%, P<0.005). Therefore, we conclude that heptanol (2 mM) decreases neurotransmitter release (given the decrease in EJP amplitude) by abolishing the nerve terminal action potential in a proportion of nerve terminals. 18 betaGA (10 microM) effectively blocks the gap junctions, but the increase in sEJP frequency suggests an additional prejunctional effect, which might involve the induction of spontaneous nerve terminal action potentials.

The impact of short term synaptic depression and stochastic vesicle dynamics on neuronal variability

PubMed Central

Reich, Steven

2014-01-01

Neuronal variability plays a central role in neural coding and impacts the dynamics of neuronal networks. Unreliability of synaptic transmission is a major source of neural variability: synaptic neurotransmitter vesicles are released probabilistically in response to presynaptic action potentials and are recovered stochastically in time. The dynamics of this process of vesicle release and recovery interacts with variability in the arrival times of presynaptic spikes to shape the variability of the postsynaptic response. We use continuous time Markov chain methods to analyze a model of short term synaptic depression with stochastic vesicle dynamics coupled with three different models of presynaptic spiking: one model in which the timing of presynaptic action potentials are modeled as a Poisson process, one in which action potentials occur more regularly than a Poisson process (sub-Poisson) and one in which action potentials occur more irregularly (super-Poisson). We use this analysis to investigate how variability in a presynaptic spike train is transformed by short term depression and stochastic vesicle dynamics to determine the variability of the postsynaptic response. We find that sub-Poisson presynaptic spiking increases the average rate at which vesicles are released, that the number of vesicles released over a time window is more variable for smaller time windows than larger time windows and that fast presynaptic spiking gives rise to Poisson-like variability of the postsynaptic response even when presynaptic spike times are non-Poisson. Our results complement and extend previously reported theoretical results and provide possible explanations for some trends observed in recorded data. PMID:23354693

Corrective Action Investigation Plan for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada (December 2002, Revision No.: 0), Including Record of Technical Change No. 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

NNSA /NSO

The Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 204 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 204 is located on the Nevada Test Site approximately 65 miles northwest of Las Vegas, Nevada. This CAU is comprised of six Corrective Action Sites (CASs) which include: 01-34-01, Underground Instrument House Bunker; 02-34-01, Instrument Bunker; 03-34-01, Underground Bunker; 05-18-02, Chemical Explosives Storage; 05-33-01, Kay Blockhouse; 05-99-02, Explosive Storage Bunker.more » Based on site history, process knowledge, and previous field efforts, contaminants of potential concern for Corrective Action Unit 204 collectively include radionuclides, beryllium, high explosives, lead, polychlorinated biphenyls, total petroleum hydrocarbons, silver, warfarin, and zinc phosphide. The primary question for the investigation is: ''Are existing data sufficient to evaluate appropriate corrective actions?'' To address this question, resolution of two decision statements is required. Decision I is to ''Define the nature of contamination'' by identifying any contamination above preliminary action levels (PALs); Decision II is to ''Determine the extent of contamination identified above PALs. If PALs are not exceeded, the investigation is completed. If PALs are exceeded, then Decision II must be resolved. In addition, data will be obtained to support waste management decisions. Field activities will include radiological land area surveys, geophysical surveys to identify any subsurface metallic and nonmetallic debris, field screening for applicable contaminants of potential concern, collection and analysis of surface and subsurface soil samples from biased locations, and step-out sampling to define the extent of contamination, as necessary. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Distinctive laterality of neural networks supporting action understanding in left- and right-handed individuals: An EEG coherence study.

PubMed

Kelly, Rachel; Mizelle, J C; Wheaton, Lewis A

2015-08-01

Prior work has demonstrated that perspective and handedness of observed actions can affect action understanding differently in right and left-handed persons, suggesting potential differences in the neural networks underlying action understanding between right and left-handed individuals. We sought to evaluate potential differences in these neural networks using electroencephalography (EEG). Right- and left-handed participants observed images of tool-use actions from egocentric and allocentric perspectives, with right- and left-handed actors performing the actions. Participants judged the outcome of the observed actions, and response accuracy and latency were recorded. Behaviorally, the highest accuracy and shortest latency was found in the egocentric perspective for right- and left-handed observers. Handedness of subject showed an effect on accuracy and latency also, where right-handed observers were faster to respond than left-handed observers, but on average were less accurate. Mu band (8-10 Hz) cortico-cortical coherence analysis indicated that right-handed observers have coherence in the motor dominant left parietal-premotor networks when looking at an egocentric right or allocentric left hands. When looking in an egocentric perspective at a left hand or allocentric right hand, coherence was lateralized to right parietal-premotor areas. In left-handed observers, bilateral parietal-premotor coherence patterns were observed regardless of actor handedness. These findings suggest that the cortical networks involved in understanding action outcomes are dependent on hand dominance, and notably right handed participants seem to utilize motor systems based on the limb seen performing the action. The decreased accuracy for right-handed participants on allocentric images could be due to asymmetrical lateralization of encoding action and motoric dominance, which may interfere with translating allocentric limb action outcomes. Further neurophysiological studies will determine the specific processes of how left- and right-handed participants understand actions. Copyright © 2015 Elsevier Ltd. All rights reserved.

An N-methyl-D-aspartate receptor-independent excitatory action of partial reduction of extracellular [Mg2+] in CA1-region of rat hippocampal slices.

PubMed

Hamon, B; Stanton, P K; Heinemann, U

1987-03-31

Partial reduction of [Mg2+]o from 2 to 1 mM markedly enhanced neuronal responses evoked by Schaffer collateral-commissural fiber stimulation in the CA1-region of rat hippocampal slices. The amplitude of extracellular population potentials recorded in the CA1-pyramidal cell layer and maximum dV/dt of extracellular population EPSP's recorded in the CA1-pyramidal apical dendritic layer were both increased. However, unlike findings from slices where Mg2+ was completely removed from the bathing medium, there was no spontaneous or evoked epileptiform activity, and the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (2-APV) did not antagonize the enhancement of evoked responses. These results indicate that, in addition to the participation of NMDA receptors in the epileptiform activity observed when Mg2+ is completely removed from the bathing medium, there is also an NMDA receptor-independent excitatory action of partial reduction of [Mg2+]o in hippocampal slices.

Superfund Record of Decision (EPA Region 7): Lehigh Portland Cement Company, Mason City, IA. (First remedial action), June 1991. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-06-28

The Lehigh Portland Cement site is composed of two areas: the 150-acre Lehigh Portland Cement Company (LPCC) cement production facility, and the 410-acre Lime Creek Nature Center (LCNC), in Mason, Gordo County, Iowa. The site overlies an aquifer that serves as a source of water for 12 nearby wells; and municipal water is obtained from a deeper aquifer. Calmus Creek borders the site and discharges to the Winnebago River, located within a mile of the site. From 1911 to the present, the LPCC has manufactured cement products. In 1981, hydrochemical tests of Blue Waters Pond on the LPCC area indicatedmore » high alkalinity. The Record of Decision (ROD) addresses the Cement Kiln Dust ground water, and surface water as a final remedy. Elevated pH of ground water and surface water also is of potential concern. The selected remedial action for all are included.« less

Digital communication support and Alzheimer's disease.

PubMed

Ekström, Anna; Ferm, Ulrika; Samuelsson, Christina

2017-08-01

Communication is one of the areas where people with dementia and their caregivers experience most challenges. The purpose of this study is to contribute to the understanding of possibilities and pitfalls of using personalized communication applications installed on tablet computers to support communication for people with dementia and their conversational partners. The study is based on video recordings of a woman, 52 years old, with Alzheimer's disease interacting with her husband in their home. The couple was recorded interacting with and without a tablet computer including a personalized communication application. The results from the present study reveal both significant possibilities and potential difficulties in introducing a digital communication device to people with dementia and their conversational partners. For the woman in the present study, the amount of interactive actions and the number of communicative actions seem to increase with the use of the communication application. The results also indicate that problems associated with dementia are foregrounded in interaction where the tablet computer is used.

Spike threshold dynamics in spinal motoneurons during scratching and swimming.

PubMed

Grigonis, Ramunas; Alaburda, Aidas

2017-09-01

Action potential threshold can vary depending on firing history and synaptic inputs. We used an ex vivo carapace-spinal cord preparation from adult turtles to study spike threshold dynamics in motoneurons during two distinct types of functional motor behaviour - fictive scratching and fictive swimming. The threshold potential depolarizes by about 10 mV within each burst of spikes generated during scratch and swim network activity and recovers between bursts to a slightly depolarized level. Slow synaptic integration resulting in a wave of membrane potential depolarization is the factor influencing the threshold potential within firing bursts during motor behaviours. Depolarization of the threshold potential decreases the excitability of motoneurons and may provide a mechanism for stabilization of the response of a motoneuron to intense synaptic inputs to maintain the motor commands within an optimal range for muscle activation. During functional spinal neural network activity motoneurons receive intense synaptic input, and this could modulate the threshold for action potential generation, providing the ability to dynamically adjust the excitability and recruitment order for functional needs. In the present study we investigated the dynamics of action potential threshold during motor network activity. Intracellular recordings from spinal motoneurons in an ex vivo carapace-spinal cord preparation from adult turtles were performed during two distinct types of motor behaviour - fictive scratching and fictive swimming. We found that the threshold of the first spike in episodes of scratching and swimming was the lowest. The threshold potential depolarizes by about 10 mV within each burst of spikes generated during scratch and swim network activity and recovers between bursts to a slightly depolarized level. Depolarization of the threshold potential results in decreased excitability of motoneurons. Synaptic inputs do not modulate the threshold of the first action potential during episodes of scratching or of swimming. There is no correlation between changes in spike threshold and interspike intervals within bursts. Slow synaptic integration that results in a wave of membrane potential depolarization rather than fast synaptic events preceding each spike is the factor influencing the threshold potential within firing bursts during motor behaviours. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Multi-scale recordings for neuroprosthetic control of finger movements.

PubMed

Baker, Justin; Bishop, William; Kellis, Spencer; Levy, Todd; House, Paul; Greger, Bradley

2009-01-01

We trained a rhesus monkey to perform individuated and combined finger flexions and extensions of the thumb, index, and middle finger. A Utah Electrode Array (UEA) was implanted into the hand region of the motor cortex contralateral to the monkey's trained hand. We also implanted a microwire electrocorticography grid (microECoG) epidurally so that it covered the UEA. The microECoG grid spanned the arm and hand regions of both the primary motor and somatosensory cortices. Previously this monkey had Implantable MyoElectric Sensors (IMES) surgically implanted into the finger muscles of the monkey's forearm. Action potentials (APs), local field potentials (LFPs), and microECoG signals were recorded from wired head-stage connectors for the UEA and microECoG grids, while EMG was recorded wirelessly. The monkey performed a finger flexion/extension task while neural and EMG data were acquired. We wrote an algorithm that uses the spike data from the UEA to perform a real-time decode of the monkey's finger movements. Also, analyses of the LFP and microECoG data indicate that these data show trial-averaged differences between different finger movements, indicating the data are potentially decodeable.

Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

PubMed Central

Boychuk, Carie R.; Gyarmati, Peter; Xu, Hong

2015-01-01

Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated. PMID:26084907

[Organization of public oral health services for early diagnosis of potentially malignant disorders in the state of Rio de Janeiro, Brazil].

PubMed

Casotti, Elisete; Monteiro, Ana Beatriz Fonseca; Castro Filho, Evelyn Lima de; Santos, Manuella Pires Dos

2016-05-01

This is a study of the organization of public health services in the state of Rio de Janeiro concerning the diagnosis of potentially malignant disorders. Secondary data from the database of the first phase of the Program for Enhancement for Access to and Quality of Primary Care were used. The implementation of actions at different levels for cancer prevention, the availability of diagnostic support services and the organization of the care network were assessed. The results show that only 58.8% of oral health teams record and monitor suspect cases; that only 47.1% reported having preferential channels for referring patients and there is great variation in waiting times to confirm the diagnosis. Local managerial and regional support actions can improve the organization of the care network for oral cancer prevention in the state.

Superfund Record of Decision (EPA Region 4): USMC Camp Lejeune Military Reservation, NC. (First remedial action), September 1992. Interim report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-23

The 500-acre Camp Lejeune Military Reservation is located 15 miles southeast of Jacksonville, in Onslow County, North Carolina. Within the site lies the Hadnot Point Industrial Area (HPIA), which was constructed in the late 1930's. It is composed of 75 buildings and facilities, which include gas stations, offices, storage yards, maintenance shops, and a dry cleaning plant. Several areas of the HPIA have been investigated for potential contamination attributed to Marine Corps activities and operations that resulted in a generation of potentially hazardous wastes. The ROD addresses an interim remedial action for the shallow aquifer at the HPIA to protectmore » human health from exposure to VOCs and metals. The primary contaminants of concern affecting the shallow ground water aquifer are VOCs, including benzene and TCE; and metals, including arsenic, chromium, and lead.« less

Incorporating Pharmacogenomics into Health Information Technology, Electronic Health Record and Decision Support System: An Overview.

PubMed

Alanazi, Abdullah

2017-02-01

As the adoption of information technology in healthcare is rising, the potentiality of moving Pharmacogenomics from benchside to bedside is aggravated. This paper reviews the current status of Pharmacogenomics (PGx) information and the attempts for incorporating them into the Electronic Health Record (EHR) system through Decision Support Systems (DSSs). Rigorous review strategies of PGx information and providing context-relevant recommendations in form of action plan- dose adjustment, lab tests rather than just information- would be ideal for making clinical recommendations out of PGx information. Lastly, realistic projections of what pharmacogenomics can provide is another important aspect in incorporating Pharmacogenomics into health information technology.

Nanoelectronics Meets Biology: From Novel Nanoscale Devices for Live Cell Recording to 3D Innervated Tissues†

PubMed Central

Duan, Xiaojie; Lieber, Charles M.

2013-01-01

High spatio-temporal resolution interfacing between electrical sensors and biological systems, from single live cells to tissues, is crucial for many areas, including fundamental biophysical studies as well as medical monitoring and intervention. This focused review summarizes recent progresses in the development and application of novel nanoscale devices for intracellular electrical recordings of action potentials, and the effort of merging electronic and biological systems seamlessly in three dimension using macroporous nanoelectronic scaffolds. The uniqueness of these nanoscale devices for minimally invasive, large scale, high spatial resolution, and three dimensional neural activity mapping will be highlighted. PMID:23946279

Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes.

PubMed

Xing, Wenlu; Gao, Chuanyu; Qi, Datun; Zhang, You; Hao, Peiyuan; Dai, Guoyou; Yan, Ganxin

2017-01-01

The mechanisms of vascular endothelial growth factor 165 (VEGF165) on electrical properties of cardiomyocytes have not been fully elucidated. The aim of this study is to test the hypothesis that VEGF165, an angiogenesis-initiating factor, affects L-type calcium currents (I Ca,L ) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). I Ca,L and action potentials (AP) were recorded by the whole-cell patch clamp method in isolated guinea-pig ventricular myocytes treated with different concentrations of VEGF165 proteins. Using a VEGFR2 inhibitor, we also tested the receptor of VEGF165 in cardiomyocytes. We found that VEGF165 increased I Ca,L in a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced I Ca,L increase. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, I Ca,L can be increased by VEGF165 in a concentration-dependent manner through binding to VEGFR2 without causing any significant alteration to action potential duration. Results of this study may further expound the safety of VEGF165 when used in the intervention of heart diseases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Thermoreception and Nociception of the Skin: A Classic Paper of Bessou and Perl and Analyses of Thermal Sensitivity during a Student Laboratory Exercise

ERIC Educational Resources Information Center

Kuhtz-Buschbeck, Johann P.; Andresen, Wiebke; Gobel, Stephan; Gilster, Rene; Stick, Carsten

2010-01-01

About four decades ago, Perl and collaborators were the first ones who unambiguously identified specifically nociceptive neurons in the periphery. In their classic work, they recorded action potentials from single C-fibers of a cutaneous nerve in cats while applying carefully graded stimuli to the skin (Bessou P, Perl ER. Response of cutaneous…

Neuromonitoring of cochlea and auditory nerve with multiple extracted parameters during induced hypoxia and nerve manipulation

NASA Astrophysics Data System (ADS)

Bohórquez, Jorge; Özdamar, Özcan; Morawski, Krzysztof; Telischi, Fred F.; Delgado, Rafael E.; Yavuz, Erdem

2005-06-01

A system capable of comprehensive and detailed monitoring of the cochlea and the auditory nerve during intraoperative surgery was developed. The cochlear blood flow (CBF) and the electrocochleogram (ECochGm) were recorded at the round window (RW) niche using a specially designed otic probe. The ECochGm was further processed to obtain cochlear microphonics (CM) and compound action potentials (CAP).The amplitude and phase of the CM were used to quantify the activity of outer hair cells (OHC); CAP amplitude and latency were used to describe the auditory nerve and the synaptic activity of the inner hair cells (IHC). In addition, concurrent monitoring with a second electrophysiological channel was achieved by recording compound nerve action potential (CNAP) obtained directly from the auditory nerve. Stimulation paradigms, instrumentation and signal processing methods were developed to extract and differentiate the activity of the OHC and the IHC in response to three different frequencies. Narrow band acoustical stimuli elicited CM signals indicating mainly nonlinear operation of the mechano-electrical transduction of the OHCs. Special envelope detectors were developed and applied to the ECochGm to extract the CM fundamental component and its harmonics in real time. The system was extensively validated in experimental animal surgeries by performing nerve compressions and manipulations.

Utility of nerve conduction studies for diagnosis of injury to the medial branch of the superficial radial nerve.

PubMed

Kon, Tomoya; Suzuki, Chieko; Hotta, Ryotaro; Funamizu, Yukihisa; Haga, Rie; Ueno, Tatsuya; Nishijima, Haruo; Arai, Akira; Nunomura, Jinichi; Nukada, Hitoshi; Tomiyama, Masahiko; Baba, Masayuki

2017-09-01

The clinical utility of nerve conduction study (NCS) for the distal medial branch of the superficial radial nerve (SRN) has not yet been clarified. Therefore, we investigated the clinical utility of NCS in patients with suspected SRN injury and compared the results with those in healthy control subjects. Bilateral NCS of the medial branch of the SRN was performed in two patients with suspected injury of the medial branch of the SRN, and in 20 healthy control subjects. A surface recording electrode was placed at the medial side of the metacarpophalangeal joint of the thumb. The SRN was then stimulated at a location 12 cm proximal from the recording electrode. The mean sensory nerve action potential in the two patients was significantly lower than that of the controls (6.75 ± 0.92 vs. 23.8 ± 8.2 μV, P  < 0.05). The side-to-side differences in sensory nerve action potential in the two patients were significantly higher than in the controls (55 ± 7.1 vs. 11 ± 7.8%, P  < 0.05). NCS may be useful for diagnosing injury of the medial branch of the SRN.

Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

PubMed Central

Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

2014-01-01

Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in intact, awake monkeys (Macaca mulatta). We recorded action potentials within ~1 ms after 0.4 ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared to sham stimulation. The methodology is compatible with standard equipment in primate laboratories, allowing for easy implementation. Application of these new tools will facilitate the refinement of next generation TMS devices, experiments, and treatment protocols. PMID:24974797

The beginning of intracellular recording in spinal neurons: Facts, reflections, and speculations☆, ☆☆

PubMed Central

Stuart, Douglas G.; Brownstone, Robert M.

2016-01-01

Intracellular (IC) recording of action potentials in neurons of the vertebrate central nervous system (CNS) was first reported by John Eccles and two colleagues, Walter Brock and John Coombs, in Dunedin, NZL in 1951/1952 and by Walter Woodbury and Harry Patton in Seattle, WA, USA in 1952. Both groups studied spinal cord neurons of the adult cat. In this review, we discuss the precedents to their notable achievement and reflect and speculate on some of the scientific and personal nuances of their work and its immediate and later impact. We then briefly discuss early achievements in IC recording in the study of CNS neurobiology in other laboratories around the world, and some of the methods that led to enhancement of CNS IC-recording techniques. Our modern understanding of CNS neurophysiology directly emanates from the pioneering endeavors of the five who wrote the seminal 1951/1952 articles. PMID:21782158

40 CFR 63.2998 - What records must I maintain?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Records of maintenance and inspections performed on the control devices. (e) If an operating parameter... which corrective actions were initiated and completed; (4) A brief description of the corrective actions...

High frequency stimulation abolishes thalamic network oscillations: an electrophysiological and computational analysis

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Hitti, Frederick L.; Chang, Su-Youne; Lee, Dongchul C.; Roberts, David W.; McIntyre, Cameron C.; Leiter, James C.

2011-08-01

Deep brain stimulation (DBS) of the thalamus has been demonstrated to be effective for the treatment of epilepsy. To investigate the mechanism of action of thalamic DBS, we examined the effects of high frequency stimulation (HFS) on spindle oscillations in thalamic brain slices from ferrets. We recorded intracellular and extracellular electrophysiological activity in the nucleus reticularis thalami (nRt) and in thalamocortical relay (TC) neurons in the lateral geniculate nucleus, stimulated the slice using a concentric bipolar electrode, and recorded the level of glutamate within the slice. HFS (100 Hz) of TC neurons generated excitatory post-synaptic potentials, increased the number of action potentials in both TC and nRt neurons, reduced the input resistance, increased the extracellular glutamate concentration, and abolished spindle wave oscillations. HFS of the nRt also suppressed spindle oscillations. In both locations, HFS was associated with significant and persistent elevation in extracellular glutamate levels and suppressed spindle oscillations for many seconds after the cessation of stimulation. We simulated HFS within a computational model of the thalamic network, and HFS also disrupted spindle wave activity, but the suppression of spindle activity was short-lived. Simulated HFS disrupted spindle activity for prolonged periods of time only after glutamate release and glutamate-mediated activation of a hyperpolarization-activated current (Ih) was incorporated into the model. Our results suggest that the mechanism of action of thalamic DBS as used in epilepsy may involve the prolonged release of glutamate, which in turn modulates specific ion channels such as Ih, decreases neuronal input resistance, and abolishes thalamic network oscillatory activity.

Instrumentation to Record Evoked Potentials for Closed-Loop Control of Deep Brain Stimulation

PubMed Central

Kent, Alexander R.; Grill, Warren M.

2012-01-01

Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000x over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

78 FR 23313 - Privacy Act of 1974: New System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... OFFICE OF PERSONNEL MANAGEMENT Privacy Act of 1974: New System of Records AGENCY: U.S. Office of Personnel Management (OPM). ACTION: Notice of amendment to system of records. SUMMARY: OPM has amended an... carriers that are outside of the scope of existing OPM systems. DATES: This action will be effective...

All-Optical Electrophysiology for Disease Modeling and Pharmacological Characterization of Neurons.

PubMed

Werley, Christopher A; Brookings, Ted; Upadhyay, Hansini; Williams, Luis A; McManus, Owen B; Dempsey, Graham T

2017-09-11

A key challenge for establishing a phenotypic screen for neuronal excitability is measurement of membrane potential changes with high throughput and accuracy. Most approaches for probing excitability rely on low-throughput, invasive methods or lack cell-specific information. These limitations stimulated the development of novel strategies for characterizing the electrical properties of cultured neurons. Among these was the development of optogenetic technologies (Optopatch) that allow for stimulation and recording of membrane voltage signals from cultured neurons with single-cell sensitivity and millisecond temporal resolution. Neuronal activity is elicited using blue light activation of the channelrhodopsin variant 'CheRiff'. Action potentials and synaptic signals are measured with 'QuasAr', a rapid and sensitive voltage-indicating protein with near-infrared fluorescence that scales proportionately with transmembrane potential. This integrated technology of optical stimulation and recording of electrical signals enables investigation of neuronal electrical function with unprecedented scale and precision. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

The effects of anticonvulsants on 4-aminopyridine-induced bursting: in vitro studies on rat peripheral nerve and dorsal roots.

PubMed Central

Lees, G.

1996-01-01

1. Aminopyridines have been used as beneficial symptomatic treatments in a variety of neurological conditions including multiple sclerosis but have been associated with considerable toxicity in the form of abdominal pain, paraesthesias and (rarely) convulsions. 2. Extracellular and intracellular recording was used to characterize action potentials in rat sciatic nerves and dorsal roots and the effects of 4-aminopyridine (4-AP). 3. In sciatic nerve trunks, 1 mM 4-AP produced pronounced after potentials at room temperature secondary to regenerative firing in affected axons (5-10 spikes per stimulus). At physiological temperatures, after potentials (2-3 spikes) were greatly attenuated in peripheral axons. 4. 4-AP evoked more pronounced and prolonged after discharges in isolated dorsal roots at 37 degrees C (3-5.5 mV and 80-100 ms succeeded by a smaller inhibitory/depolarizing voltage shift) which were used to assess the effects of anticonvulsants. 5. Phenytoin, carbamazepine and lamotrigine dose-dependently reduced the area of 4-AP-induced after potentials at 100 and 320 microM but the amplitude of compound action potentials (evoked at 0.5 Hz) was depressed in parallel. 6. The tonic block of sensory action potentials by all three drugs (at 320 microM) was enhanced by high frequency stimulation (5-500 Hz). 7. The lack of selectivity of these frequency-dependent Na+ channel blockers for burst firing compared to low-frequency spikes, is discussed in contrast to their effects on 4-AP-induced seizures and paroxysmal activity in CNS tissue (which is associated with large and sustained depolarizing plateau potentials). 8. In conclusion, these in vitro results confirm the marked sensitivity of sensory axons to 4-AP (the presumptive basis for paraesthesias). Burst firing was not preferentially impaired at relatively high concentrations suggesting that anticonvulsants will not overcome the toxic peripheral actions of 4-AP in neurological patients. PMID:8821551

32 CFR 505.12 - Privacy Act enforcement actions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... AUTHORITIES AND PUBLIC RELATIONS ARMY PRIVACY ACT PROGRAM § 505.12 Privacy Act enforcement actions. (a... record under false pretenses; or (iii) Maintaining a system of records without first meeting the public...

The linear synchronization measures of uterine EMG signals: Evidence of synchronized action potentials during propagation.

PubMed

Domino, Malgorzata; Pawlinski, Bartosz; Gajewski, Zdzislaw

2016-11-01

Evaluation of synchronization between myoelectric signals can give new insights into the functioning of the complex system of porcine myometrium. We propose a model of uterine contractions according to the hypothesis of action potentials similarity which is possible to detect during propagation in the uterine wall. We introduce similarity measures based on the concept of synchronization as used in matching linear signals such as electromyographic (EMG) time series data. The aim was to present linear measures to assess synchronization between contractions in different topographic regions of the uterus. We use the cross-correlation function (ƒx,y[l], ƒy,z[l]) and the cross-coherence function (Cxy[ƒ], Cyz[ƒ]) to assess synchronization between three data series of a diestral uterine EMG bundles in porcine reproductive tract. Spontaneous uterine activity was recorded using telemetry method directly by three-channel transmitter and three silver bipolar needle electrodes sutured on different topographic regions of the reproductive tract in the sow. The results show the usefulness of the cross-coherence function in that synchronization between uterine horn and corpus uteri for multiple action potentials (bundles) could be observed. The EMG bundles synchronization may be used to investigate the direction and velocity of EMG signals propagation in porcine reproductive tract. Copyright © 2016 Elsevier Inc. All rights reserved.

GABAergic circuits control input-spike coupling in the piriform cortex.

PubMed

Luna, Victor M; Schoppa, Nathan E

2008-08-27

Odor coding in mammals is widely believed to involve synchronized gamma frequency (30-70 Hz) oscillations in the first processing structure, the olfactory bulb. How such inputs are read in downstream cortical structures however is not known. Here we used patch-clamp recordings in rat piriform cortex slices to examine cellular mechanisms that shape how the cortex integrates inputs from bulb mitral cells. Electrical stimulation of mitral cell axons in the lateral olfactory tract (LOT) resulted in excitation of pyramidal cells (PCs), which was followed approximately 10 ms later by inhibition that was highly reproducible between trials in its onset time. This inhibition was somatic in origin and appeared to be driven through a feedforward mechanism, wherein GABAergic interneurons were directly excited by mitral cell axons. The precise inhibition affected action potential firing in PCs in two distinct ways. First, by abruptly terminating PC excitation, it limited the PC response to each EPSP to exactly one, precisely timed action potential. In addition, inhibition limited the summation of EPSPs across time, such that PCs fired action potentials in strong preference for synchronized inputs arriving in a time window of <5 ms. Both mechanisms would help ensure that PCs respond faithfully and selectively to mitral cell inputs arriving as a synchronized gamma frequency pattern.

Amphetamine Augments Action Potential-Dependent Dopaminergic Signaling in the Striatum in Vivo

PubMed Central

Ramsson, Eric S.; Covey, Daniel P.; Daberkow, David P.; Litherland, Melissa T.; Juliano, Steven A.; Garris, Paul A.

2011-01-01

Amphetamine (AMPH) is thought to disrupt normal patterns of action potential-dependent dopaminergic signaling by depleting dopamine (DA) vesicular stores and promoting non-exocytotic DA efflux. Voltammetry in brain slices concurrently demonstrates these key drug effects, along with competitive inhibition of neuronal DA uptake. Here we perform comparable kinetic and voltammetric analyses in vivo to determine whether AMPH acts qualitatively and quantitatively similar in the intact brain. Fast-scan cyclic voltammetry measured extracellular DA in dorsal and ventral striata of urethane-anesthetized rats. Electrically evoked recordings were analyzed to determine Km and Vmax for DA uptake and vesicular DA release, while background voltammetric current indexed basal DA concentration. AMPH (0.5, 3, and 10 mg/kg i.p.) robustly increased evoked DA responses in both striatal subregions. The predominant contributor to these elevated levels was competitive uptake inhibition, as exocytotic release was unchanged in the ventral striatum and only modestly decreased in the dorsal striatum. Increases in basal DA levels were not detected. These results are consistent with AMPH augmenting action potential-dependent dopaminergic signaling in vivo across a wide, behaviorally relevant dose range. Future work should be directed at possible causes for the distinct in vitro and in vivo pharmacology of AMPH. PMID:21443523

[Effects of transections and electrical coagulations in the medulla oblongata upon the activities in the respiratory muscles of the crucian carp (author's transl)].

PubMed

Fukuda, H

1975-06-01

The following conclusions may be drawn from the results in this work. The respiratory cycles are formed by the neuronal machinery in the reticular formation under the posterior part of the vagal motor nucleus. The motor neurones or the neuronal networks composing the motor nucleus of the respiratory muscles tonically discharge the action potentials, when the neurones or the networks are released from the inhibitory influences of the interneurones connecting the neuronal machinery to the motor neurones. Furthermore, the interneurones probably generate the tonic discharges after removing the inhibitory influences of the other interneurones or the neuronal machinery on them. A reflex mouth closing is elicited by a mechanical stimulus applying on the upper lip. The motor neurones of the m. adductor mandibulae are activated via only one synapse in the reflex. The reflex action potentials recorded from the motor nerve reduce in amplitude at the resting phase of the nerve in the respiratory cycles. These results suggest that the respiratory motor neurones are by nature spontaneous generators of the tonic action potentials and, in the time of the normal breathing, the tonic activity is interrupted by an inhibitory influence of the neuronal machinery generating the respiratory cycles.

Inhibition of the reverse mode of the Na+/Ca2+ exchange by KB-R7943 augments arrhythmogenicity in the canine heart during rapid heart rates.

PubMed

Shinada, Takuro; Hirayama, Yoshiyuki; Maruyama, Mitsunori; Ohara, Toshihiko; Yashima, Masaaki; Kobayashi, Yoshinori; Atarashi, Hirotsugu; Takano, Teruo

2005-07-01

To test the hypothesis that the reverse mode of the Na+/Ca2+ exchange augmented by a rapid heart rate has an antiarrhythmic effect by shortening the action potential duration, we examined the effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), a selective inhibitor of the reverse mode of the Na+/Ca2+ exchange, to attenuate this effect. We recorded the electrocardiogram, monophasic action potential (MAP), and left ventricular pressure in canine beating hearts. In comparison to the control, KB-R7943 significantly increased the QTc value and MAP duration. MAP alternans and left ventricular pressure alternans were observed after changing the cycle length to 300 milliseconds in the control studies. KB-R7943 magnified both types of alternans and produced spatially discordant alternans between right and left ventricles. Early after-depolarizations and nonsustained ventricular tachycardia occurred in the presence of KB-R7943. Our data suggest that the reverse mode of the Na+/Ca2+ exchange may contribute to suppression of arrhythmias by abbreviating action potential duration under pathophysiological conditions. This conclusion is based on further confirmation by future studies of the specificity of KB-R7943 for block of the reverse mode of the Na+/Ca2+ exchange.

Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

PubMed Central

Chang, Eric H.; Frattini, Stephen A.; Robbiati, Sergio; Huerta, Patricio T.

2013-01-01

State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field potentials (LFPs) from populations of neurons and action potentials from individual cells, as the animal engages in experimentally relevant tasks. Chronically implanted microdrives allow for brain recordings to last over periods of several weeks. Miniaturized drives and lightweight components allow for these long-term recordings to occur in small mammals, such as mice. By using tetrodes, which consist of tightly braided bundles of four electrodes in which each wire has a diameter of 12.5 μm, it is possible to isolate physiologically active neurons in superficial brain regions such as the cerebral cortex, dorsal hippocampus, and subiculum, as well as deeper regions such as the striatum and the amygdala. Moreover, this technique insures stable, high-fidelity neural recordings as the animal is challenged with a variety of behavioral tasks. This manuscript describes several techniques that have been optimized to record from the mouse brain. First, we show how to fabricate tetrodes, load them into driveable tubes, and gold-plate their tips in order to reduce their impedance from MΩ to KΩ range. Second, we show how to construct a custom microdrive assembly for carrying and moving the tetrodes vertically, with the use of inexpensive materials. Third, we show the steps for assembling a commercially available microdrive (Neuralynx VersaDrive) that is designed to carry independently movable tetrodes. Finally, we present representative results of local field potentials and single-unit signals obtained in the dorsal subiculum of mice. These techniques can be easily modified to accommodate different types of electrode arrays and recording schemes in the mouse brain. PMID:23851569

Proceedings of a Workshop on Antarctic Meteorite Stranding Surfaces

NASA Technical Reports Server (NTRS)

Cassidy, W. A. (Editor); Whillans, I. M. (Editor)

1990-01-01

The discovery of large numbers of meteorites on the Antarctic Ice Sheet is one of the most exciting developments in polar science in recent years. The meteorites are found on areas of ice called stranding surfaces. Because of the sudden availability of hundreds, and then thousands, of new meteorite specimens at these sites, the significance of the discovery of meteorite stranding surfaces in Antarctica had an immediate and profound impact on planetary science, but there is also in this discovery an enormous, largely unrealized potential to glaciology for records of climatic and ice sheet changes. The glaciological interest derives from the antiquity of the ice in meteorite stranding surfaces. This exposed ice covers a range of ages, probably between zero and more than 500,000 years. The Workshop on Antarctic Meteorite Stranding Surfaces was convened to explore this potential and to devise a course of action that could be recommended to granting agencies. The workshop recognized three prime functions of meteorite stranding surfaces. They provide: (1) A proxy record of climatic change (i.e., a long record of climatic change is probably preserved in the exposed ice stratigraphy); (2) A proxy record of ice volume change; and (3) A source of unique nonterrestrial material.

'Fingerprints' of central stimulatory drug effects by means of quantitative radioelectroencephalography in the rat (tele-stereo-EEG).

PubMed

Dimpfel, W; Spüler, M; Nickel, B; Tibes, U

1986-01-01

The new electrophysiological model earlier described as stereo-EEG is extended now to allow recording from the freely moving rat by means of a telemetric device. Chronic implantation of 4 electrodes into the brain allows simultaneous transmission of field potentials from frontal cortex, hippocampus, striatum and reticular formation. Frequency analysis of these potentials results in a drug-specific 'fingerprint' which cannot only be used to compare different chemicals with each other but also to detect onset and time dependence of drug actions. Application of the model to the question if fenetylline has its own intrinsic mode of action or merely develops its stimulatory effect after metabolic separation into its molecular moieties amphetamine and theophylline (prodrug hypothesis) revealed that fenetylline indeed displays its own stimulatory effect to the same extent and at a similar time course as amphetamine and theophylline. The 'fingerprint' as obtained by the analysis of the action of fenetylline in the rat resembles closely that obtained after the application of theophylline with respect to decreased alpha activity, but resembles amphetamine with respect to beta 1 activity. Thus the applied method allows studying structure function relationships as the action of fenetylline seems to reflect both its molecular moieties.

Evoked potentials in final epoch of self-initiated hand movement: A study in patients with depth electrodes.

PubMed

Kukleta, Miloslav; Damborská, Alena; Turak, Baris; Louvel, Jacques

2017-07-01

Comparison between the intended and performed motor action can be expected to occur in the final epoch of a voluntary movement. In search for electrophysiological correlates of this mental process the purpose of the current study was to identify intracerebral sites activated in final epoch of self-paced voluntary movement. Intracerebral EEG was recorded from 235 brain regions of 42 epileptic patients who performed self-paced voluntary movement task. Evoked potentials starting at 0 to 243ms after the peak of averaged, rectified electromyogram were identified in 21 regions of 13 subjects. The mean amplitude value of these late movement potentials (LMP) was 56.4±27.5μV. LMPs were observed in remote regions of mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices. Closely before the LMP onset, a significant increase of phase synchronization was observed in all EEG record pairs in 9 of 10 examined subjects; p<0.001, Mann-Whitney U test. In conclusion, mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices seem to represent integral functionally linked parts of network activated in final epoch of self-paced voluntary movement. Activation of this large-scale neuronal network was suggested to reflect a comparison process between the intended and actually performed motor action. Our results contribute to better understanding of neural mechanisms underlying goal-directed behavior crucial for creation of agentive experience. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding

PubMed Central

Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

2016-01-01

Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information. PMID:27304526

Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding.

PubMed

Huang, Chao; Resnik, Andrey; Celikel, Tansu; Englitz, Bernhard

2016-06-01

Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information.

Left atrial booster function in valvular heart disease.

PubMed

Heidenreich, F P; Shaver, J A; Thompson, M E; Leonard, J J

1970-09-01

This study was designed to assess atrial booster pump action in valvular heart disease and to dissect booster pump from reservoir-conduit functions. In five patients with aortic stenosis and six with mitral stenosis, sequential atrioventricular (A-V) pacing was instituted during the course of diagnostic cardiac catheterization. Continuous recording of valvular gradient allowed estimation of flow for each cardiac cycle by transposition of the Gorlin formula. Left ventricular ejection time and left ventricular stroke work in aortic stenosis or left ventricular mean systolic pressure in mitral stenosis were also determined. Control observations were recorded during sequential A-V pacing with well-timed atrial systole. Cardiac cycles were then produced with no atrial contraction but undisturbed atrial reservoir function by intermittently interrupting the atrial pacing stimulus during sequential A-V pacing. This intervention significantly reduced valvular gradient, flow, left ventricular ejection time, and left ventricular mean systolic pressure or stroke work. Cardiac cycles were then produced with atrial booster action eliminated by instituting synchronous A-V pacing. The resultant simultaneous contraction of the atrium and ventricle not only eliminated effective atrial systole but also placed atrial systole during the normal period of atrial reservoir function. This also significantly reduced all the hemodynamic measurements. However, comparison of the magnitude of change from these two different pacing interventions showed no greater impairment of hemodynamic state when both booster pump action and reservoir function were impaired than when booster pump action alone was impaired. The study confirms the potential benefit of well placed atrial booster pump action in valvular heart disease in man.

K(ATP) channel blocker HMR 1883 reduces monophasic action potential shortening during coronary ischemia in anesthetised pigs.

PubMed

Wirth, K J; Uhde, J; Rosenstein, B; Englert, H C; Gögelein, H; Schölkens, B A; Busch, A E

2000-02-01

ATP-sensitive potassium channels (KATP) open during myocardial ischemia. The ensuing repolarising potassium efflux shortens the action potential. Accumulation of extracellular potassium is able to partially depolarise the membrane, reducing the upstroke velocity of the action potential and thereby impairing impulse conduction. Both mechanisms are believed to be involved in the development of reentrant arrhythmias during cardiac ischemia. The sulfonylthiourea HMR 1883 (1-[[5-[2-(5-chloro-O-anisamido)ethyl]-methoxyphenyl]sulfonyl]-3-m ethylthiourea) was designed as a cardioselective KATP channel blocker for the prevention of arrhythmic sudden death in patients with ischemic heart disease. The aim of this study was to show that this compound, which has already shown antifibrillatory efficacy in dogs and rats, is able to inhibit ischemic changes of the action potential induced by coronary artery occlusion in anesthetised pigs. Action potentials were taken in situ with the technique of monophasic action potential (MAP) recording. In a control group (n=7), three consecutive occlusions of a small branch of the left circumflex coronary artery resulted in reproducible reductions in MAP duration and a decrease in upstroke velocity. In a separate group (n=7), HMR 1883 (3 mg/kg i.v.) significantly (P<0.05) reduced the ischemia-induced shortening of the MAP: during the first and second control occlusion of the coronary artery in the HMR 1883-group, MAP50 duration shortened from 218.5 +/- 3.0 ms to 166.7 +/- 3.3 ms and from 219.7 +/- 4.5 ms to 164.9 +/- 1.8 ms, respectively. After HMR 1883, during the third occlusion, MAP duration decreased from 226.9 +/- 3.6 ms to 205.3 +/- 4.3 ms only corresponding to 59% inhibition. HMR 1883 also improved the upstroke velocity of the MAP, which was depressed by ischemia: in the two preceding control occlusions ischemia prolonged the time to peak of the MAP, an index for upstroke velocity, from 10.83 +/- 0.43 ms to 39.42 +/- 1.60 ms and from 12.97 +/- 0.40 ms to 37.17 +/- 2.98 ms, respectively. With HMR 1883, time to peak during ischemia rose from 12.42 +/- 0.51 ms to 25.53+/-2.51 ms only, corresponding to an average inhibitory effect of 53.4%. The irregular repolarisation contour of the ischemic MAP was also improved. In conclusion, the present results indicate that HMR 1883 effectively blocks myocardial KATP channels during coronary ischemia in anesthetised pigs, preventing an excessive shortening of the action potential and improving excitation propagation.

Monolithically Integrated μLEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals

PubMed Central

Wu, Fan; Stark, Eran; Ku, Pei-Cheng; Wise, Kensall D.; Buzsáki, György; Yoon, Euisik

2015-01-01

SUMMARY We report a scalable method to monolithically integrate microscopic light emitting diodes (μLEDs) and recording sites onto silicon neural probes for optogenetic applications in neuroscience. Each μLED and recording site has dimensions similar to a pyramidal neuron soma, providing confined emission and electrophysiological recording of action potentials and local field activity. We fabricated and implanted the four-shank probes, each integrated with 12 μLEDs and 32 recording sites, into the CA1 pyramidal layer of anesthetized and freely moving mice. Spikes were robustly induced by 60 nW light power, and fast population oscillations were induced at the microwatt range. To demonstrate the spatiotemporal precision of parallel stimulation and recording, we achieved independent control of distinct cells ~50 μm apart and of differential somatodendritic compartments of single neurons. The scalability and spatiotemporal resolution of this monolithic optogenetic tool provides versatility and precision for cellular-level circuit analysis in deep structures of intact, freely moving animals. PMID:26627311

Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms

PubMed Central

Hepler, Justin; Albarracin, Dolores

2018-01-01

Although robust evidence indicates that action initiation can occur unconsciously and unintentionally, the literature on action inhibition suggests that inhibition requires both conscious thought and intentionality. In prior research demonstrating automatic inhibition in response to unconsciously processed stimuli, the unconscious stimuli had previously been consciously associated with an inhibitory response within the context of the experiment, and participants had consciously formed a goal to activate inhibition processes when presented with the stimuli (because task instructions required participants to engage in inhibition when the stimuli occurred). Therefore, prior work suggests that some amount of conscious thought and intentionality are required for inhibitory control. In the present research, we recorded event-related potentials during two go/no-go experiments in which participants were subliminally primed with general action/inaction concepts that had never been consciously associated with task-specific responses. We provide the first demonstration that inhibitory control processes can be modulated completely unconsciously and unintentionally. PMID:23747649

Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens.

PubMed

Stenner, Max-Philipp; Dürschmid, Stefan; Rutledge, Robb B; Zaehle, Tino; Schmitt, Friedhelm C; Kaufmann, Jörn; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J; Schoenfeld, Mircea Ariel

2016-10-01

The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here we provide electrophysiological evidence for a more direct, i.e., online, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha/beta oscillations (10-30 Hz) before and around the time of movements. This perimovement alpha/beta desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate choices in a decision making task. A similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution. Copyright © 2016 the American Physiological Society.

Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens

PubMed Central

Dürschmid, Stefan; Rutledge, Robb B.; Zaehle, Tino; Schmitt, Friedhelm C.; Kaufmann, Jörn; Voges, Jürgen; Heinze, Hans-Jochen; Dolan, Raymond J.; Schoenfeld, Mircea Ariel

2016-01-01

The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here we provide electrophysiological evidence for a more direct, i.e., online, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha/beta oscillations (10–30 Hz) before and around the time of movements. This perimovement alpha/beta desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate choices in a decision making task. A similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution. PMID:27486103

40 CFR 63.6660 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... years following the date of each occurrence, measurement, maintenance, corrective action, report, or... years after the date of each occurrence, measurement, maintenance, corrective action, report, or record...

22 CFR 225.115 - IRB records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... attendance at the meetings; actions taken by the IRB; the vote on these actions including the number of... this policy shall be retained for at least 3 years, and records relating to research which is conducted...

7 CFR 1c.115 - IRB records.

Code of Federal Regulations, 2010 CFR

2010-01-01

... attendance at the meetings; actions taken by the IRB; the vote on these actions including the number of... policy shall be retained for at least 3 years, and records relating to research which is conducted shall...

Aldosterone down-regulates the slowly activated delayed rectifier potassium current in adult guinea pig cardiomyocytes.

PubMed

Lv, Yankun; Bai, Song; Zhang, Hua; Zhang, Hongxue; Meng, Jing; Li, Li; Xu, Yanfang

2015-12-01

There is emerging evidence that the mineralocorticoid hormone aldosterone is associated with arrhythmias in cardiovascular disease. However, the effect of aldosterone on the slowly activated delayed rectifier potassium current (IK s ) remains poorly understood. The present study was designed to investigate the modulation of IK s by aldosterone. Adult guinea pigs were treated with aldosterone for 28 days via osmotic pumps. Standard glass microelectrode recordings and whole-cell patch-clamp techniques were used to record action potentials in papillary muscles and IK s in ventricular cardiomyocytes. The aldosterone-treated animals exhibited a prolongation of the QT interval and action potential duration with a higher incidence of early afterdepolarizations. Patch-clamp recordings showed a significant down-regulation of IK s density in the ventricular myocytes of these treated animals. These aldosterone-induced electrophysiological changes were fully prevented by a combined treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist. In addition, in in vitro cultured ventricular cardiomyocytes, treatment with aldosterone (sustained exposure for 24 h) decreased the IK s density in a concentration-dependent manner. Furthermore, a significant corresponding reduction in the mRNA/protein expression of IKs channel pore and auxiliary subunits, KCNQ1 and KCNE1 was detected in ventricular tissue from the aldosterone-treated animals. Aldosterone down-regulates IK s by inhibiting the expression of KCNQ1 and KCNE1, thus delaying the ventricular repolarization. These results provide new insights into the mechanism underlying K(+) channel remodelling in heart disease and may explain the highly beneficial effects of MR antagonists in HF. © 2015 The British Pharmacological Society.

Corrective Action Decision Document for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada, Rev. No. 0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robert Boehlecke

2004-04-01

The six bunkers included in CAU 204 were primarily used to monitor atmospheric testing or store munitions. The ''Corrective Action Investigation Plan (CAIP) for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada'' (NNSA/NV, 2002a) provides information relating to the history, planning, and scope of the investigation; therefore, it will not be repeated in this CADD. This CADD identifies potential corrective action alternatives and provides a rationale for the selection of a recommended corrective action alternative for each CAS within CAU 204. The evaluation of corrective action alternatives is based on process knowledge and the results of investigative activitiesmore » conducted in accordance with the CAIP (NNSA/NV, 2002a) that was approved prior to the start of the Corrective Action Investigation (CAI). Record of Technical Change (ROTC) No. 1 to the CAIP (approval pending) documents changes to the preliminary action levels (PALs) agreed to by the Nevada Division of Environmental Protection (NDEP) and DOE, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This ROTC specifically discusses the radiological PALs and their application to the findings of the CAU 204 corrective action investigation. The scope of this CADD consists of the following: (1) Develop corrective action objectives; (2) Identify corrective action alternative screening criteria; (3) Develop corrective action alternatives; (4) Perform detailed and comparative evaluations of corrective action alternatives in relation to corrective action objectives and screening criteria; and (5) Recommend and justify a preferred corrective action alternative for each CAS within CAU 204.« less

Superfund record of decision (EPA Region 9): Aircraft Control and Warning Site, Mather Air Force Base, CA, December 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

This decision document, a Record of Decision (ROD), presents the selected remedial action for the AC W Site, Installation Restoration Program (IRP) Site 12, at Mather Air Force Base (AFB), Sacramento County, California. Reports indicate that from 1958 to 1966 waste solvents and transformer oils were disposed in a waste disposal pipe in the AC W area. Investigations conducted as part of the Air Force Installation Restoration Program (IRP) failed to locate the waste disposal pipe but did find trichloroethylene (TCE) contamination in the shallow water bearing zone (SWBZ) in the AC W area. The SWBZ is classified as amore » potential source of drinking water by the State of California, although it is not currently used in the AC W area. The selected remedy will address the potential threat to human health posed by TCE contamination in groundwater (primarily in the SWBZ).« less

40 CFR 63.3131 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... following the date of each occurrence, measurement, maintenance, corrective action, report, or record, as... least 2 years after the date of each occurrence, measurement, maintenance, corrective action, report, or...

40 CFR 63.7343 - In what form and how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... for 5 years following the date of each occurrence, measurement, maintenance, corrective action, report... occurrence, measurement, maintenance, corrective action, report, or record, according to § 63.10(b)(1). You...

Motor resonance may originate from sensorimotor experience.

PubMed

Petroni, Agustín; Baguear, Federico; Della-Maggiore, Valeria

2010-10-01

In humans, the motor system can be activated by passive observation of actions or static pictures with implied action. The origin of this facilitation is of major interest to the field of motor control. Recently it has been shown that sensorimotor learning can reconfigure the motor system during action observation. Here we tested directly the hypothesis that motor resonance arises from sensorimotor contingencies by measuring corticospinal excitability in response to abstract non-action cues previously associated with an action. Motor evoked potentials were measured from the first dorsal interosseus (FDI) while human subjects observed colored stimuli that had been visually or motorically associated with a finger movement (index or little finger abduction). Corticospinal excitability was higher during the observation of a colored cue that preceded a movement involving the recorded muscle than during the observation of a different colored cue that preceded a movement involving a different muscle. Crucially this facilitation was only observed when the cue was associated with an executed movement but not when it was associated with an observed movement. Our findings provide solid evidence in support of the sensorimotor hypothesis of action observation and further suggest that the physical nature of the observed stimulus mediating this phenomenon may in fact be irrelevant.

Lateralization of motor excitability during observation of bimanual signs.

PubMed

Möttönen, Riikka; Farmer, Harry; Watkins, Kate E

2010-08-01

Viewing another person's hand actions enhances excitability in an observer's left and right primary motor (M1) cortex. We aimed to determine whether viewing communicative hand actions alters this bilateral sensorimotor resonance. Using single-pulse transcranial magnetic stimulation (TMS), we measured excitability in the left and right M1 while right-handed non-signing participants observed bimanual communicative hand actions, i.e., meaningful signs in British Sign Language. TMS-induced motor evoked potentials were recorded from hand muscles during sign observation before and after teaching the participants to associate meanings with half of the signs. Before this teaching, when participants did not know that the presented hand actions were signs, excitability of left and right M1 was modulated equally. After learning the meanings of half the signs, excitability of the left, but not right, M1 was significantly enhanced. This left-lateralized enhancement of M1 excitability occurred during observation of signs with known and unknown meanings. The findings suggest that awareness of the communicative nature of another person's hand actions strengthens sensorimotor resonance in the left M1 cortex and alters hemispheric balance during action observation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

High-performance, polymer-based direct cellular interfaces for electrical stimulation and recording

NASA Astrophysics Data System (ADS)

Kim, Seong-Min; Kim, Nara; Kim, Youngseok; Baik, Min-Seo; Yoo, Minsu; Kim, Dongyoon; Lee, Won-June; Kang, Dong-Hee; Kim, Sohee; Lee, Kwanghee; Yoon, Myung-Han

2018-04-01

Due to the trade-off between their electrical/electrochemical performance and underwater stability, realizing polymer-based, high-performance direct cellular interfaces for electrical stimulation and recording has been very challenging. Herein, we developed transparent and conductive direct cellular interfaces based on a water-stable, high-performance poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) film via solvent-assisted crystallization. The crystallized PEDOT:PSS on a polyethylene terephthalate (PET) substrate exhibited excellent electrical/electrochemical/optical characteristics, long-term underwater stability without film dissolution/delamination, and good viability for primarily cultured cardiomyocytes and neurons over several weeks. Furthermore, the highly crystallized, nanofibrillar PEDOT:PSS networks enabled dramatically enlarged surface areas and electrochemical activities, which were successfully employed to modulate cardiomyocyte beating via direct electrical stimulation. Finally, the high-performance PEDOT:PSS layer was seamlessly incorporated into transparent microelectrode arrays for efficient, real-time recording of cardiomyocyte action potentials with a high signal fidelity. All these results demonstrate the strong potential of crystallized PEDOT:PSS as a crucial component for a variety of versatile bioelectronic interfaces.

The action of ether and methoxyflurane on synaptic transmission in isolated preparations of the mammalian cortex.

PubMed Central

Richards, C D; Russell, W J; Smaje, J C

1975-01-01

1. The actions of ether and methoxyflurane on the evoked potentials of in vitro preparations of the guinea-pig olfactory cortex were studied. Following stimulation of the lateral olfactory tract (l.o.t.) evoked potentials could be recorded from the cortical surface; these potentials consisted of an initial wave (the compound action potential of the l.o.t.) followed by a negative field potential which was associated with the synchronous excitation of many superficial excitatory synapses (population e.p.s.p.). Superimposed on the population e.p.s.p. was a number of positive peaks. These positive peaks reflect the synchronous discharge of many neurones and so have been called population spikes. 2. When ether or methoxyflurane was added to the gas stream that superfused the surface of the preparations, the population e.p.s.p.s. and population spikes were depressed at lower concentrations than those required to depress the compound action potential of the afferent fibres. 3. The evoked activity of individual cells in the cortex was depressed by ether and methoxyflurane. However, five of the twelve cells tested in ether showed an increase in their evoked activity at concentrations below 4-5%, but at higher concentrations these cells also became depressed. 4. Both ether and methoxyflurane depressed the sensitivity of cortical neurones to iontophoretically applied L-glutamate and may similarly depress the sensitivity of the post-synaptic membrane to the released transmitter substance. 5. Neither anaesthetic appeared to increase the threshold depolarization required for nerve impulse generation. Thus, the decrease of the discharge of the post-synaptic cells was primarily caused by a depression of chemical transmission. 6. Ether caused some cells in the cortex to alter their normal pattern of synaptically evoked discharge and both anaesthetics induced similar changes during excitation by glutamate. PMID:168356

Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

PubMed

Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

2015-11-25

The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main compartments: dendritic, somatic, and axonal. How the neurons receive information, process it, and pass on new information depends upon how these three compartments operate. While it has long been assumed that axons are simply for conducting information from the cell body to the synapses, here we demonstrate that the axons of different types of interneurons, the inhibitory cells, possess differing electrophysiological properties. This result implies that differing types of interneurons perform different tasks in the cortex, not only through their anatomical connections, but also through how their axons operate. Copyright © 2015 the authors 0270-6474/15/3515555-13$15.00/0.

Calcium responses to synaptically activated bursts of action potentials and their synapse-independent replay in cultured networks of hippocampal neurons.

PubMed

Bengtson, C Peter; Kaiser, Martin; Obermayer, Joshua; Bading, Hilmar

2013-07-01

Both synaptic N-methyl-d-aspartate (NMDA) receptors and voltage-operated calcium channels (VOCCs) have been shown to be critical for nuclear calcium signals associated with transcriptional responses to bursts of synaptic input. However the direct contribution to nuclear calcium signals from calcium influx through NMDA receptors and VOCCs has been obscured by their concurrent roles in action potential generation and synaptic transmission. Here we compare calcium responses to synaptically induced bursts of action potentials with identical bursts devoid of any synaptic contribution generated using the pre-recorded burst as the voltage clamp command input to replay the burst in the presence of blockers of action potentials or ionotropic glutamate receptors. Synapse independent replays of bursts produced nuclear calcium responses with amplitudes around 70% of their original synaptically generated signals and were abolished by the L-type VOCC blocker, verapamil. These results identify a major direct source of nuclear calcium from local L-type VOCCs whose activation is boosted by NMDA receptor dependent depolarization. The residual component of synaptically induced nuclear calcium signals which was both VOCC independent and NMDA receptor dependent showed delayed kinetics consistent with a more distal source such as synaptic NMDA receptors or internal stores. The dual requirement of NMDA receptors and L-type VOCCs for synaptic activity-induced nuclear calcium dependent transcriptional responses most likely reflects a direct somatic calcium influx from VOCCs whose activation is amplified by synaptic NMDA receptor-mediated depolarization and whose calcium signal is boosted by a delayed input from distal calcium sources mostly likely entry through NMDA receptors and release from internal stores. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. Copyright © 2013 Elsevier B.V. All rights reserved.

Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone.

PubMed

Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles

2014-02-01

Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.

40 CFR 63.8495 - In what form and for how long must I keep my records?

Code of Federal Regulations, 2010 CFR

2010-07-01

... years following the date of each occurrence, measurement, maintenance, corrective action, report, or..., measurement, maintenance, corrective action, report, or record, according to § 63.10(b)(1). You may keep the...

Stimulus onset predictability modulates proactive action control in a Go/No-go task

PubMed Central

Berchicci, Marika; Lucci, Giuliana; Spinelli, Donatella; Di Russo, Francesco

2015-01-01

The aim of the study was to evaluate whether the presence/absence of visual cues specifying the onset of an upcoming, action-related stimulus modulates pre-stimulus brain activity, associated with the proactive control of goal-directed actions. To this aim we asked 12 subjects to perform an equal probability Go/No-go task with four stimulus configurations in two conditions: (1) uncued, i.e., without any external information about the timing of stimulus onset; and (2) cued, i.e., with external visual cues providing precise information about the timing of stimulus onset. During task both behavioral performance and event-related potentials (ERPs) were recorded. Behavioral results showed faster response times in the cued than uncued condition, confirming existing literature. ERPs showed novel results in the proactive control stage, that started about 1 s before the motor response. We observed a slow rising prefrontal positive activity, more pronounced in the cued than the uncued condition. Further, also pre-stimulus activity of premotor areas was larger in cued than uncued condition. In the post-stimulus period, the P3 amplitude was enhanced when the time of stimulus onset was externally driven, confirming that external cueing enhances processing of stimulus evaluation and response monitoring. Our results suggest that different pre-stimulus processing come into play in the two conditions. We hypothesize that the large prefrontal and premotor activities recorded with external visual cues index the monitoring of the external stimuli in order to finely regulate the action. PMID:25964751

Prolonged intra-myocardial growth hormone administration ameliorates post-infarction electrophysiologic remodeling in rats.

PubMed

Kontonika, Marianthi; Barka, Eleonora; Roumpi, Maria; La Rocca, Vassilios; Lekkas, Panagiotis; Daskalopoulos, Evangelos P; Vilaeti, Agapi D; Baltogiannis, Giannis G; Vlahos, Antonios P; Agathopoulos, Simeon; Kolettis, Theofilos M

2017-02-01

Experimental studies indicate improved ventricular function after treatment with growth hormone (GH) post-myocardial infarction, but its effect on arrhythmogenesis is unknown. Here, we assessed the medium-term electrophysiologic remodeling after intra-myocardial GH administration in (n = 33) rats. GH was released from an alginate scaffold, injected around the ischemic myocardium after coronary ligation. Two weeks thereafter, ventricular tachyarrhythmias were induced by programmed electrical stimulation. Monophasic action potentials were recorded from the infarct border, coupled with evaluation of electrical conduction and repolarization from a multi-electrode array. The arrhythmia score was lower in GH-treated rats than in alginate-treated rats or controls. The shape and the duration of the action potential at the infarct border were preserved, and repolarization-dispersion was attenuated after GH; moreover, voltage rise was higher and activation delay was shorter. GH normalized also right ventricular parameters. Intra-myocardial GH preserved electrical conduction and repolarization-dispersion at the infarct border and decreased the incidence of induced tachyarrhythmias in rats post-ligation. The long-term antiarrhythmic potential of GH merits further study.

Human neural tuning estimated from compound action potentials in normal hearing human volunteers

NASA Astrophysics Data System (ADS)

Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

2015-12-01

The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

Nanoelectronics meets biology: from new nanoscale devices for live-cell recording to 3D innervated tissues.

PubMed

Duan, Xiaojie; Lieber, Charles M

2013-10-01

High spatiotemporal resolution interfaces between electrical sensors and biological systems, from single live cells to tissues, is crucial for many areas, including fundamental biophysical studies as well as medical monitoring and intervention. Herein, we summarize recent progress in the development and application of novel nanoscale devices for intracellular electrical recording of action potentials and the effort of merging electronic and biological systems seamlessly in three dimensions by using macroporous nanoelectronic scaffolds. The uniqueness of these nanoscale devices for minimally invasive, large-scale, high spatial resolution, and three-dimensional neural activity mapping are highlighted. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps.

PubMed

Yokawa, K; Kagenishi, T; Pavlovic, A; Gall, S; Weiland, M; Mancuso, S; Baluška, F

2017-12-11

Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Scalable Electrophysiological Investigation of iPS Cell-Derived Cardiomyocytes Obtained by a Lentiviral Purification Strategy

PubMed Central

Friedrichs, Stephanie; Malan, Daniela; Voss, Yvonne; Sasse, Philipp

2015-01-01

Disease-specific induced pluripotent stem (iPS) cells can be generated from patients and differentiated into functional cardiomyocytes for characterization of the disease and for drug screening. In order to obtain pure cardiomyocytes for automated electrophysiological investigation, we here report a novel non-clonal purification strategy by using lentiviral gene transfer of a puromycin resistance gene under the control of a cardiac-specific promoter. We have applied this method to our previous reported wild-type and long QT syndrome 3 (LQTS 3)-specific mouse iPS cells and obtained a pure cardiomyocyte population. These cells were investigated by action potential analysis with manual and automatic planar patch clamp technologies, as well as by recording extracellular field potentials using a microelectrode array system. Action potentials and field potentials showed the characteristic prolongation at low heart rates in LQTS 3-specific, but not in wild-type iPS cell-derived cardiomyocytes. Hence, LQTS 3-specific cardiomyocytes can be purified from iPS cells with a lentiviral strategy, maintain the hallmarks of the LQTS 3 disease and can be used for automated electrophysiological characterization and drug screening. PMID:26237021

Dating, synthesis, and interpretation of palaeoclimatic records of the Last Glacial cycle and model-data integration: advances by the INTIMATE (INTegration of Ice-core, MArine and TErrestrial records) COST Action ES0907

NASA Astrophysics Data System (ADS)

Rasmussen, Sune O.; Birks, Hilary H.; Blockley, Simon P. E.; Brauer, Achim; Hajdas, Irka; Hoek, Wim Z.; Lowe, J. John; Moreno, Ana; Renssen, Hans; Roche, Didier M.; Svensson, Anders M.; Valdes, Paul; Walker, Mike J. C.

2014-12-01

Since 2010, the INTIMATE (INTegration of Ice-core, MArine and TErrestrial records) network has been operating as a COST Action (designated ES0907). This paper outlines the accomplishments of the INTIMATE COST Action in the context of how the INTIMATE ideas have evolved during the network's twenty-year life span, and highlights a number of challenges that can guide further work. In the second part of the paper, the contributions that comprise this INTIMATE special issue are introduced.

48 CFR 970.5204-3 - Access to and ownership of records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... negotiation records; records on ethics, employee concerns; records generated during the course of responding... headquarters); (3) Records relating to any procurement action by the Contractor, except for records that under...

A portable microelectrode array recording system incorporating cultured neuronal networks for neurotoxin detection.

PubMed

Pancrazio, Joseph J; Gray, Samuel A; Shubin, Yura S; Kulagina, Nadezhda; Cuttino, David S; Shaffer, Kara M; Eisemann, Kevin; Curran, Anthony; Zim, Bret; Gross, Guenter W; O'Shaughnessy, Thomas J

2003-10-01

Cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds, have been suggested to be useful for both screening known analytes and unknown compounds for acute neuropharmacologic effects. Extracellular recording from cultured neuronal networks provides a means for extracting physiologically relevant activity, i.e. action potential firing, in a noninvasive manner conducive for long-term measurements. Previous work from our laboratory described prototype portable systems capable of high signal-to-noise extracellular recordings from cardiac myocytes. The present work describes a portable system tailored to monitoring neuronal extracellular potentials that readily incorporates standardized microelectrode arrays developed by and in use at the University of North Texas. This system utilizes low noise amplifier and filter boards, a two-stage thermal control system with integrated fluidics and a graphical user interface for data acquisition and control implemented on a personal computer. Wherever possible, off-the-shelf components have been utilized for system design and fabrication. During use with cultured neuronal networks, the system typically exhibits input referred noise levels of only 4-6 microVRMS, such that extracellular potentials exceeding 40 microV can be readily resolved. A flow rate of up to 1 ml/min was achieved while the cell recording chamber temperature was maintained within a range of 36-37 degrees C. To demonstrate the capability of this system to resolve small extracellular potentials, pharmacological experiments with cultured neuronal networks have been performed using ion channel blockers, tetrodotoxin and tityustoxin. The implications of the experiments for neurotoxin detection are discussed.

Clinical significance of the summating potential-action potential ratio and the action potential latency difference for condensation and rarefaction clicks in Meniere's disease.

PubMed

Ohashi, Toru; Nishino, Hirohito; Arai, Yoko; Hyodo, Makoto; Takatsu, Mitsuharu

2009-04-01

This study was aimed to elucidate the diagnostic significance of the summating potential (SP)-action potential (AP) ratio and the AP latency difference between condensation and rarefaction clicks (AP con-rar difference) in Meniere's disease. The AP and SP were recorded transtympanically in 67 patients with definite Meniere's disease. The SP/AP ratio and the AP con-rar difference were assessed in terms of 1) their interrelationship, 2) their relationship to hearing level, and 3) the rate of occurrence of abnormal values according to the stages of Meniere's disease. No correlation was found between the SP/AP ratio and the AP con-rar difference. Neither the SP/AP ratio in general nor the AP con-rar difference was correlated with the hearing level. However, enhanced values of the SP/AP ratio (0.35 or higher) were moderately correlated with the hearing level (r = 0.51), and their occurrence rate was 55.2%. An increased AP con-rar difference (0.13 ms or longer) was not correlated with the hearing level, and its occurrence rate was 50.2%; it appeared most frequently at stage 3 (p <0.05). An enhanced SP/AP ratio might not always indicate the presence of endolymphatic hydrops associated with an increase in endolymphatic pressure. An increased AP con-rar difference might reflect the presence of a biased basilar membrane resulting from an increased endolymphatic pressure, and hence it is diagnostically essential to simultaneously evaluate the SP/AP ratio and the AP con-rar difference.

Electrophysiology and Innervation of the Photosensitive Epistellar Body in the Lesser Octopus Eledone cirrhosa.

PubMed

Cobb, C S; Williamson, R

1998-08-01

The innervation and responses to light of the cephalopod epistellar body were investigated in preparations isolated from the stellate ganglia of the lesser or northern octopus, Eledone cirrhosa. Extracellular generator potentials in response to flashes of light were recorded from these photosensitive vesicles, with the amplitude of the response being found to be dependent upon the intensity of the flash and the level of ambient illumination. Intracellular recordings from photoreceptor cells of the epistellar body showed that they had resting potentials of about -49 +/- 7 mV (mean +/- SD, n = 43) and were depolarized by flashes of white, but not red (>650 nm) light. The evoked depolarization consisted of a transient component, followed by a steady plateau in which the amplitude of the depolarization was well correlated with the log of the stimulus intensity. The evoked depolarizations induced action potentials in the photoreceptor cells, with the frequency of firing being well correlated with the stimulus intensity. The morphologies of individual photoreceptor cells were visualized by intracellular injections of the fluorescent dye Lucifer yellow, and the path of the epistellar nerve across the stellate ganglion, into the pallial nerve, toward the brain was traced using the lipophilic dye Di-I. This pathway was confirmed physiologically by recording light-evoked responses from the cut end of the pallial nerve.

The ERP Effects of Combined Cognitive Training on Intention-Based and Stimulus-Based Actions in Older Chinese Adults.

PubMed

Niu, Ya-Nan; Zhu, Xinyi; Li, Juan; Fu, Jiang-Ning

2016-01-01

Age-related decreases in action are caused by neuromuscular weakness and cognitive decline. Although physical interventions have been reported to have beneficial effects on cognitive function in older adults, whether cognitive training improves action-related function remains unclear. In this study, we investigated the effects of combined cognitive training on intention-based and stimulus-based actions in older adults using event-related potentials (ERPs). A total of 26 healthy older adults (16 in the training group and 10 in the control group) participated in the study. The training group received 16 sessions of cognitive training, including eight sessions of executive function training and eight sessions of memory strategy training. Before and after training, both groups of participants underwent cognitive assessments and ERP recordings during both the acquisition and test phases with a motor cognitive paradigm. During the acquisition phase, subjects were asked to press one of two keys, either using a self-selected (intention-based) method or based on the preceding stimulus (stimulus-based). During the test phase, subjects were asked to respond to the pre-cues with either congruent or incongruent tasks. Using ERP indices-including readiness potential, P3 and contingent negative variation to identify motor preparation, stimulus processing and interference effect, respectively-we revealed the effects of training on both intention-based and stimulus-based actions. The correlations were also computed between the improved cognitive performance and the ERP amplitudes. It was shown that the improved executive function might extend substantial benefits to both actions, whereas associative memory may be specifically related to the bidirectional action-effect association of intention-based action, although the training effect of memory was absent during the insufficient training hours. In sum, the present study provided empirical evidence demonstrating that action could benefit from cognitive training. www.chictr.org.cn, identifier: ChiCTR-OON-16007793.

Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.

PubMed

Cheng, Hongwei; Cannell, Mark B; Hancox, Jules C

2017-03-01

Transient outward potassium current (I to ) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of I to may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I to This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I to Whole cell patch-clamp recordings of I to and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10  μ mol/L NS5806 increased ventricular I to with a leftward shift in I to activation and accelerated restitution. At higher concentrations, stimulation of I to was followed by inhibition. The EC 50 for stimulation was 1.6  μ mol/L and inhibition had an IC 50 of 40.7  μ mol/L. NS5806 only inhibited atrial I to (IC 50 of 18  μ mol/L) and produced a modest leftward shifts in I to activation and inactivation, without an effect on restitution. 10  μ mol/L NS5806 shortened ventricular action potential duration (APD) at APD 20 -APD 90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na + channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I to NS5806 discriminates between rabbit ventricular and atrial I to, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I to . © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

76 FR 81827 - Declassification of National Security Information

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... prompt decision on the appeal. (b) [Reserved] Sec. 1260.82 What actions must NARA take with information... Declassification of National Security Information AGENCY: National Archives and Records Administration. ACTION... related to declassification of classified national security information in records transferred to NARA's...

Vestibular Response to Electrical Stimulation of the Otolith Organs. Implications in the Development of A Vestibular Implant for the Improvement of the Sensation of Gravitoinertial Accelerations.

PubMed

Ramos de Miguel, Angel; Falcon Gonzalez, Juan Carlos; Ramos Macias, Angel

2017-08-01

Electrical stimulation of the utricular and saccular portions of the vestibular nerve improves stability in patients suffering from vestibular dysfunction. The main objective of this study was to evaluate a new technique, vestibular response telemetry (VRT), for measuring the electrically evoked vestibular compound action potential (saccular and utricular) after stimulating the otolith organ (saccular and utricular) in adults. This study used evidence that the otolith organ can be electrically stimulated in order to develop a new vestibular implant design to improve the sensation of gravitoinertial acceleration. Four adult patients were evaluated by using a variety of measurement procedures with novel VRT software. VRT values were obtained by stimulating with three full-band Nucleus CI24RE (ST) electrodes. Specific stimuli were used. Simultaneously, electrical ocular vestibular evoked myogenic potentials (eoVEMPs) were recorded in the contralateral side. Electrically evoked compound action potentials were obtained in 10 of the 12 electrodes tested, and eoVEMPs were recorded when VRT was present. In addition to the validation of this technique, a set of default clinical test parameters was established. The VRT response morphology consisted of a biphasic waveform with an initial negative peak (N1) followed by a positive peak (P1), and latencies were typically 400 μs for N1 and 800 μs for P1. The consequences for the development of a vestibular implant for the improvement of gravitoinertial acceleration sensation are also presented. The VRT measurement technique has been shown to be a useful tool to record neural response on the otolith organ, and thus it is a convenient tool to evaluate whether the implanted electrodes provide a neural response or not. This can be used for the early development of vestibular implants to improve gravitoinertial acceleration sensation.

Feasibility of Gathering Depreciation Information from Existing Sources for US Army Installation Accrual Accounting Systems.

DTIC Science & Technology

1981-12-01

concerning actions needed to prevent destruction of existing information, correct property accounting systems so that future information is recorded...concerning actions needed to prevent destruction of existing informa- tion, correct property accounting systems so that future ii~formation is recorded...destroyed unless certain Department of the Army regulations are changed. Five of the fourteen recommendations address the actions needed to ensure that an

Installation Restoration Program. Phase II--Confirmation/Quantification. Stage 1.

DTIC Science & Technology

1985-03-01

four phases. Phase I, Initial Assessment/ Records Search, is designed to identify possible hazardous waste contami- nated sites and potential...7 71 -. - - IL’ -, 1% 33 AihlIII Is 33 n~iL t iiC UII! ii CL C LU 1-3, Phase II, Confirmation and Quantification, is designed to confirm the...additional monitoring data upon which design of mitigative actions are based. In Phase III, Technology Base Development, appropriate technology is selected and

Superfund record of decision (EPA Region 4): USMC Camp Lejeune Military Reservation, operable unit 4, Jacksonville, NC, January 16, 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-05-01

This operable unit consists of Sites 41 and 74. The remedial actions are designed to prevent future potential exposure by implementing institutional controls. These controls include: (1) designate the sites as `restricted` or `limited use` areas, within the base master plan; (2) prohibit the installation of potable water supply wells within the vicinity of the sites: and (3) implement a groundwater, surface water and sediment monitoring program.

Axillary nerve injury associated with sports.

PubMed

Lee, Sangkook; Saetia, Kriangsak; Saha, Suparna; Kline, David G; Kim, Daniel H

2011-11-01

The aim of this retrospective study was to present and investigate axillary nerve injuries associated with sports. This study retrospectively reviewed 26 axillary nerve injuries associated with sports between the years 1985 and 2010. Preoperative status of the axillary nerve was evaluated by using the Louisiana State University Health Science Center (LSUHSC) grading system published by the senior authors. Intraoperative nerve action potential recordings were performed to check nerve conduction and assess the possibility of resection. Neurolysis, suture, and nerve grafts were used for the surgical repair of the injured nerves. In 9 patients with partial loss of function and 3 with complete loss, neurolysis based on nerve action potential recordings was the primary treatment. Two patients with complete loss of function were treated with resection and suturing and 12 with resection and nerve grafting. The minimum follow-up period was 16 months (mean 20 months). The injuries were associated with the following sports: skiing (12 cases), football (5), rugby (2), baseball (2), ice hockey (2), soccer (1), weightlifting (1), and wrestling (1). Functional recovery was excellent. Neurolysis was performed in 9 cases, resulting in an average functional recovery of LSUHSC Grade 4.2. Recovery with graft repairs averaged LSUHSC Grade 3 or better in 11 of 12 cases Surgical repair can restore useful deltoid function in patients with sports-associated axillary nerve injuries, even in cases of severe stretch-contusion injury.

Evaluation of the myoelectrical activity of the equine ileum infected with Strongylus vulgaris larvae.

PubMed

Berry, C R; Merritt, A M; Burrows, C F; Campbell, M; Drudge, J H

1986-01-01

Five weanling ponies were subjected to an intensive 6-week deworming program after which 4 Ag-AgCl bipolar electrodes were implanted surgically on the distal ileum. For 3 hours each day for 5 consecutive days, ileal myoelectrical activity was recorded from fed ponies under 3 sequential conditions: preinoculation, after oral administration of 1,000 killed Strongylus vulgaris infective larvae (3 ponies), and after oral administration of 1,000 live S vulgaris infective larvae. Recordings were analyzed for slow wave frequency, percentage duration of phases I, II, and III of the migrating myoelectrical complex (MMC), and the frequency of distinct, rapidly migrating action-potential complexes within phase 2 of the MMC. After administration of live and killed infected 3rd-stage larvae, there was a marked increase in the number of disrupted phase III complexes, and a significant (P less than 0.001) increase in the number of migrating action-potential complexes. In addition, after inoculation of live 3rd-stage larvae, there was a significant increase (P less than 0.001) in the percentage of time that the MMC was occupied by prolonged periods devoid of spike activity (phase I). The results indicate that S vulgaris larval mucosal penetration and submucosal migration can cause changes in ileal myoelectrical activity that could cause colic, and that larval antigen alone within the lumen may disrupt ileal motility.

Multifocal Fluorescence Microscope for Fast Optical Recordings of Neuronal Action Potentials

PubMed Central

Shtrahman, Matthew; Aharoni, Daniel B.; Hardy, Nicholas F.; Buonomano, Dean V.; Arisaka, Katsushi; Otis, Thomas S.

2015-01-01

In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera’s native frame rate. We demonstrate that this approach is capable of recording Ca2+ transients resulting from APs in neurons labeled with the Ca2+ sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

Do Not Resonate with Actions: Sentence Polarity Modulates Cortico-Spinal Excitability during Action-Related Sentence Reading

PubMed Central

Liuzza, Marco Tullio; Candidi, Matteo; Aglioti, Salvatore Maria

2011-01-01

Background Theories of embodied language suggest that the motor system is differentially called into action when processing motor-related versus abstract content words or sentences. It has been recently shown that processing negative polarity action-related sentences modulates neural activity of premotor and motor cortices. Methods and Findings We sought to determine whether reading negative polarity sentences brought about differential modulation of cortico-spinal motor excitability depending on processing hand-action related or abstract sentences. Facilitatory paired-pulses Transcranial Magnetic Stimulation (pp-TMS) was applied to the primary motor representation of the right-hand and the recorded amplitude of induced motor-evoked potentials (MEP) was used to index M1 activity during passive reading of either hand-action related or abstract content sentences presented in both negative and affirmative polarity. Results showed that the cortico-spinal excitability was affected by sentence polarity only in the hand-action related condition. Indeed, in keeping with previous TMS studies, reading positive polarity, hand action-related sentences suppressed cortico-spinal reactivity. This effect was absent when reading hand action-related negative polarity sentences. Moreover, no modulation of cortico-spinal reactivity was associated with either negative or positive polarity abstract sentences. Conclusions Our results indicate that grammatical cues prompting motor negation reduce the cortico-spinal suppression associated with affirmative action sentences reading and thus suggest that motor simulative processes underlying the embodiment may involve even syntactic features of language. PMID:21347305

Carbon nanotube multi-electrode array chips for noninvasive real-time measurement of dopamine, action potentials, and postsynaptic potentials.

PubMed

Suzuki, Ikuro; Fukuda, Mao; Shirakawa, Keiichi; Jiko, Hideyasu; Gotoh, Masao

2013-11-15

Multi-electrode arrays (MEAs) can be used for noninvasive, real-time, and long-term recording of electrophysiological activity and changes in the extracellular chemical microenvironment. Neural network organization, neuronal excitability, synaptic and phenotypic plasticity, and drug responses may be monitored by MEAs, but it is still difficult to measure presynaptic activity, such as neurotransmitter release, from the presynaptic bouton. In this study, we describe the development of planar carbon nanotube (CNT)-MEA chips that can measure both the release of the neurotransmitter dopamine as well as electrophysiological responses such as field postsynaptic potentials (fPSPs) and action potentials (APs). These CNT-MEA chips were fabricated by electroplating the indium-tin oxide (ITO) microelectrode surfaces. The CNT-plated ITO electrode exhibited electrochemical response, having much higher current density compared with the bare ITO electrode. Chronoamperometric measurements using these CNT-MEA chips detected dopamine at nanomolar concentrations. By placing mouse striatal brain slices on the CNT-MEA chip, we successfully measured synaptic dopamine release from spontaneous firings with a high S/N ratio of 62. Furthermore, APs and fPSPs were measured from cultured hippocampal neurons and slices with high temporal resolution and a 100-fold greater S/N ratio. Our CNT-MEA chips made it possible to measure neurotransmitter dopamine (presynaptic activities), postsynaptic potentials, and action potentials, which have a central role in information processing in the neuronal network. CNT-MEA chips could prove useful for in vitro studies of stem cell differentiation, drug screening and toxicity, synaptic plasticity, and pathogenic processes involved in epilepsy, stroke, and neurodegenerative diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

The assessment of electrophysiological activity in human-induced pluripotent stem cell-derived cardiomyocytes exposed to dimethyl sulfoxide and ethanol by manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Hyun, Sung-Ae; Seo, Joung-Wook

2017-09-01

Recently, electrophysiological activity has been effectively measured in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to predict drug-induced arrhythmia. Dimethyl sulfoxide (DMSO) and ethanol have been used as diluting agents in many experiments. However, the maximum DMSO and ethanol concentrations that can be effectively used in the measurement of electrophysiological parameters in hiPSC-CMs-based patch clamp and multi-electrode array (MEA) have not been fully elucidated. We investigated the effects of varying concentrations of DMSO and ethanol used as diluting agents on several electrophysiological parameters in hiPSC-CMs using patch clamp and MEA. Both DMSO and ethanol at concentrations>1% in external solution resulted in osmolality >400mOsmol/kg, but pH was not affected by either agent. Neither DMSO nor ethanol led to cell death at the concentrations examined. However, resting membrane potential, action potential amplitude, action potential duration at 90% and 40%, and corrected field potential duration were decreased significantly at 1% ethanol concentration. DMSO at 1% also significantly decreased the sodium spike amplitude. In addition, the waveform of action potential and field potential was recorded as irregular at 3% concentrations of both DMSO and ethanol. Concentrations of up to 0.3% of either agent did not affect osmolality, pH, cell death, or electrophysiological parameters in hiPSC-CMs. Our findings suggest that 0.3% is the maximum concentration at which DMSO or ethanol should be used for dilution purposes in hiPSC-CMs-based patch clamp and MEA. Copyright © 2017 Elsevier Inc. All rights reserved.

WH Craib: a critical account of his work

PubMed Central

Naidoo, DP

2009-01-01

Summary Summary One hundred years after its introduction, the ECG remains the most commonly used cardiovascular laboratory procedure. It fulfils all the requirements of a diagnostic test: it is non-invasive, simple to record, highly reproducible and can be applied serially. It is the first laboratory test to be performed in a patient with chest pain, syncope or cardiac arrhythmias. It is also a prognostic tool that aids in risk stratification and clinical management. Among the many South Africans who have made remarkable contributions in the field of electrocardiography, Don Craib was the first to investigate the changing patterns of the ECG action potential in isolated skeletal muscle strips under varying conditions. It was during his stay at Johns Hopkins Hospital in Baltimore and Sir Thomas Lewis laboratory in London that Craib made singular observations about the fundamental origins of electrical signals in the skeletal muscle, and from these developed his hypothesis on the generation of the action potential in the electrocardiogram. His proposals went contrary to scientific opinion at the time and he was rebuffed by the scientific community. Frank Wilson subsequently went on to develop Craib’s doublet hypothesis into the dipole theory, acknowledging Craib’s work. Today the dipole theory is fundamental to the understanding of the spread of electrical activation in the myocardium and the genesis of the action potential. PMID:19287808

EMR documentation of physician-patient communication following genomic counseling for actionable complex disease and pharmacogenomic results.

PubMed

Sweet, K; Sturm, A C; Schmidlen, T; Hovick, S; Peng, J; Manickam, K; Salikhova, A; McElroy, J; Scheinfeldt, L; Toland, A E; Roberts, J S; Christman, M

2017-04-01

Genomic risk information for potentially actionable complex diseases and pharmacogenomics communicated through genomic counseling (GC) may motivate physicians and patients to take preventive actions. The Ohio State University-Coriell Personalized Medicine Collaborative is a randomized trial to measure the effects of in-person GC on chronic disease patients provided with multiplex results. Nine personalized genomic risk reports were provided to patients through a web portal, and to physicians via electronic medical record (EMR). Active arm participants (98, 39% female) received GC within 1 month of report viewing; control arm subjects (101, 54% female) could access counseling 3-months post-report viewing. We examined whether GC affected documentation of physician-patient communication by reviewing the first clinical note following the patient's GC visit or report upload to the EMR. Multivariable logistic regression modeling estimated the independent effect of GC on physician-patient communication, as intention to treat (ITT) and per protocol (PP), adjusted for physician educational intervention. Counselees in the active arm had more physician-patient communications than control subjects [ITT, odds ratio (OR): 3.76 (95% confidence interval (CI): 1.38-10.22, p < 0.0094); PP, OR: 5.53 (95% CI: 2.20-13.90, p = 0.0017). In conclusion, GC appreciably affected physician-patient communication following receipt of potentially actionable genomic risk information. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bootstrapping agency: How control-relevant information affects motivation.

PubMed

Karsh, Noam; Eitam, Baruch; Mark, Ilya; Higgins, E Tory

2016-10-01

How does information about one's control over the environment (e.g., having an own-action effect) influence motivation? The control-based response selection framework was proposed to predict and explain such findings. Its key tenant is that control relevant information modulates both the frequency and speed of responses by determining whether a perceptual event is an outcome of one's actions or not. To test this framework empirically, the current study examines whether and how temporal and spatial contiguity/predictability-previously established as being important for one's sense of agency-modulate motivation from control. In 5 experiments, participants responded to a cue, potentially triggering a perceptual effect. Temporal (Experiments 1a-c) and spatial (Experiments 2a and b) contiguity/predictability between actions and their potential effects were experimentally manipulated. The influence of these control-relevant factors was measured, both indirectly (through their effect on explicit judgments of agency) and directly on response time and response frequency. The pattern of results was highly consistent with the control-based response selection framework in suggesting that control relevant information reliably modulates the impact of "having an effect" on different levels of action selection. We discuss the implications of this study for the notion of motivation from control and for the empirical work on the sense of agency. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

[Identification and mapping of prescribed nursing actions for patients in an adult ICU].

PubMed

Salgado, Patricia Oliveira; Tannure, Meire Chucre; Oliveira, Cleydson Rodrigues; Chianca, Tânia Couto Machado

2012-01-01

Descriptive study that aimed to identify nursing actions prescribed by nurses in the medical records of patients admitted to an Intensive Care Unit (ICU) for adults, in Belo Horizonte (MG), the terms used, their frequency and map the actions to the Theory of Basic Human Needs and NIC interventions. It was obtained a sample of 44 patient records. It was identified 2,260 nursing actions. After exclusion of repetitions, it was found 124 different actions. All nursing actions have been mapped to physiological needs and also to NIC interventions. It was obtained 100% of agreement among experts in the validation of the mapping process. It is suggested that similar studies in ICUs from other locations and different contexts / specialties should be driven to identify nursing actions developed and its evolution.

Systematic review of compound action potentials as predictors for cochlear implant performance.

PubMed

van Eijl, Ruben H M; Buitenhuis, Patrick J; Stegeman, Inge; Klis, Sjaak F L; Grolman, Wilko

2017-02-01

The variability in speech perception between cochlear implant users is thought to result from the degeneration of the auditory nerve. Degeneration of the auditory nerve, histologically assessed, correlates with electrophysiologically acquired measures, such as electrically evoked compound action potentials (eCAPs) in experimental animals. To predict degeneration of the auditory nerve in humans, where histology is impossible, this paper reviews the correlation between speech perception and eCAP recordings in cochlear implant patients. PubMed and Embase. We performed a systematic search for articles containing the following major themes: cochlear implants, evoked potentials, and speech perception. Two investigators independently conducted title-abstract screening, full-text screening, and critical appraisal. Data were extracted from the remaining articles. Twenty-five of 1,429 identified articles described a correlation between speech perception and eCAP attributes. Due to study heterogeneity, a meta-analysis was not feasible, and studies were descriptively analyzed. Several studies investigating presence of the eCAP, recovery time constant, slope of the amplitude growth function, and spatial selectivity showed significant correlations with speech perception. In contrast, neural adaptation, eCAP threshold, and change with varying interphase gap did not significantly correlate with speech perception in any of the identified studies. Significant correlations between speech perception and parameters obtained through eCAP recordings have been documented in literature; however, reporting was ambiguous. There is insufficient evidence for eCAPs as a predictive factor for speech perception. More research is needed to further investigate this relation. Laryngoscope, 2016 127:476-487, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Carbachol induces burst firing of dopamine cells in the ventral tegmental area by promoting calcium entry through L-type channels in the rat

PubMed Central

Zhang, Lei; Liu, Yudan; Chen, Xihua

2005-01-01

Enhanced activity of the central dopamine system has been implicated in many psychiatric disorders including schizophrenia and addiction. Besides terminal mechanisms that boost dopamine levels at the synapse, the cell body of dopamine cells enhances terminal dopamine concentration through encoding action potentials in bursts. This paper presents evidence that burst firing of dopamine cells in the ventral tegmental area was under cholinergic control using nystatin-perforated patch clamp recording from slice preparations. The non-selective cholinergic agonist carbachol excited the majority of recorded neurones, an action that was not affected by blocking glutamate and GABA ionotropic receptors. Twenty per cent of dopamine cells responded to carbachol with robust bursting, an effect mediated by both muscarinic and nicotinic cholinoceptors postsynaptically. Burst firing induced as such was completely dependent on calcium entry as it could be blocked by cadmium and more specifically the L-type blocker nifedipine. In the presence of the sodium channel blocker tetrodotoxin, carbachol induced membrane potential oscillation that had similar kinetics and frequency as burst firing cycles and could also be blocked by cadmium and nifedipine. Direct activation of the L-type channel with Bay K8644 induced strong bursting which could be blocked by nifedipine but not by depleting internal calcium stores. These results indicate that carbachol increases calcium entry into the postsynaptic cell through L-type channels to generate calcium-dependent membrane potential oscillation and burst firing. This could establish the L-type channel as a target for modulating the function of the central dopamine system in disease conditions. PMID:16081481

43 CFR 30.273 - What action will the judge take to record title?

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROBATE HEARINGS PROCEDURES Tribal Purchase of Interests Under Special Statutes § 30.273 What action will...) File the complete record, including the decision, with the LTRO as provided in § 30.233; (c) Furnish a... decision to each interested party. ...

Stimfit: quantifying electrophysiological data with Python

PubMed Central

Guzman, Segundo J.; Schlögl, Alois; Schmidt-Hieber, Christoph

2013-01-01

Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals. PMID:24600389

Dopamine modulates an intrinsic mGluR5-mediated depolarization underlying prefrontal persistent activity

PubMed Central

Sidiropoulou, Kyriaki; Lu, Fang-Min; Fowler, Melissa A.; Xiao, Rui; Phillips, Christopher; Ozkan, Emin D.; Zhu, Michael X.; White, Francis J.; Cooper, Donald C.

2009-01-01

Intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons are capable of maintaining persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory possibly by modulating intrinsic neuronal properties. Here we use patch-clamp recording of layer 5 PFC pyramidal neurons to identify an action potential burst-evoked intrinsic mGluR5-mediated postsynaptic depolarization that initiates an activated state. Depolarization occurs in the absence of recurrent synaptic activity and is reduced by a postsynaptic dopamine D1/5 receptor pathway. The depolarization is substantially diminished following behavioral sensitization to cocaine; moreover the D1/5 receptor modulation is lost. We propose the burst-evoked intrinsic depolarization to be a novel form of short-term cellular memory that is modulated by dopamine and cocaine experience. PMID:19169252

An ultra low-power CMOS automatic action potential detector.

PubMed

Gosselin, Benoit; Sawan, Mohamad

2009-08-01

We present a low-power complementary metal-oxide semiconductor (CMOS) analog integrated biopotential detector intended for neural recording in wireless multichannel implants. The proposed detector can achieve accurate automatic discrimination of action potential (APs) from the background activity by means of an energy-based preprocessor and a linear delay element. This strategy improves detected waveforms integrity and prompts for better performance in neural prostheses. The delay element is implemented with a low-power continuous-time filter using a ninth-order equiripple allpass transfer function. All circuit building blocks use subthreshold OTAs employing dedicated circuit techniques for achieving ultra low-power and high dynamic range. The proposed circuit function in the submicrowatt range as the implemented CMOS 0.18- microm chip dissipates 780 nW, and it features a size of 0.07 mm(2). So it is suitable for massive integration in a multichannel device with modest overhead. The fabricated detector succeeds to automatically detect APs from underlying background activity. Testbench validation results obtained with synthetic neural waveforms are presented.

Correlates of a single cortical action potential in the epidural EEG

PubMed Central

Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel

2015-01-01

To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity.

PubMed

Zanos, Theodoros P; Silverman, Harold A; Levy, Todd; Tsaava, Tea; Battinelli, Emily; Lorraine, Peter W; Ashe, Jeffrey M; Chavan, Sangeeta S; Tracey, Kevin J; Bouton, Chad E

2018-05-22

The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1β-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve. Copyright © 2018 the Author(s). Published by PNAS.