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Sample records for action potentials spikes

  1. Metabolic Energy of Action Potentials Modulated by Spike Frequency Adaptation

    PubMed Central

    Yi, Guo-Sheng; Wang, Jiang; Li, Hui-Yan; Wei, Xi-Le; Deng, Bin

    2016-01-01

    Spike frequency adaptation (SFA) exists in many types of neurons, which has been demonstrated to improve their abilities to process incoming information by synapses. The major carrier used by a neuron to convey synaptic signals is the sequences of action potentials (APs), which have to consume substantial metabolic energies to initiate and propagate. Here we use conductance-based models to investigate how SFA modulates the AP-related energy of neurons. The SFA is attributed to either calcium-activated K+ (IAHP) or voltage-activated K+ (IM) current. We observe that the activation of IAHP or IM increases the Na+ load used for depolarizing membrane, while produces few effects on the falling phase of AP. Then, the metabolic energy involved in Na+ current significantly increases from one AP to the next, while for K+ current it is less affected. As a consequence, the total energy cost by each AP gets larger as firing rate decays down. It is also shown that the minimum Na+ charge needed for the depolarization of each AP is unaffected during the course of SFA. This indicates that the activation of either adaptation current makes APs become less efficient to use Na+ influx for their depolarization. Further, our simulations demonstrate that the different biophysical properties of IM and IAHP result in distinct modulations of metabolic energy usage for APs. These investigations provide a fundamental link between adaptation currents and neuronal energetics, which could facilitate to interpret how SFA participates in neuronal information processing. PMID:27909394

  2. Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism.

    PubMed

    Porcello, Darrell M; Ho, Chi Shun; Joho, Rolf H; Huguenard, John R

    2002-03-01

    Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

  3. Action potential initiation in a two-compartment model of pyramidal neuron mediated by dendritic Ca(2+) spike.

    PubMed

    Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

    2017-04-03

    Dendritic Ca(2+) spike endows cortical pyramidal cell with powerful ability of synaptic integration, which is critical for neuronal computation. Here we propose a two-compartment conductance-based model to investigate how the Ca(2+) activity of apical dendrite participates in the action potential (AP) initiation to affect the firing properties of pyramidal neurons. We have shown that the apical input with sufficient intensity triggers a dendritic Ca(2+) spike, which significantly boosts dendritic inputs as it propagates to soma. Such event instantaneously shifts the limit cycle attractor of the neuron and results in a burst of APs, which makes its firing rate reach a plateau steady-state level. Delivering current to two chambers simultaneously increases the level of neuronal excitability and decreases the threshold of input-output relation. Here the back-propagating APs facilitate the initiation of dendritic Ca(2+) spike and evoke BAC firing. These findings indicate that the proposed model is capable of reproducing in vitro experimental observations. By determining spike initiating dynamics, we have provided a fundamental link between dendritic Ca(2+) spike and output APs, which could contribute to mechanically interpreting how dendritic Ca(2+) activity participates in the simple computations of pyramidal neuron.

  4. Action potential initiation in a two-compartment model of pyramidal neuron mediated by dendritic Ca2+ spike

    PubMed Central

    Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin

    2017-01-01

    Dendritic Ca2+ spike endows cortical pyramidal cell with powerful ability of synaptic integration, which is critical for neuronal computation. Here we propose a two-compartment conductance-based model to investigate how the Ca2+ activity of apical dendrite participates in the action potential (AP) initiation to affect the firing properties of pyramidal neurons. We have shown that the apical input with sufficient intensity triggers a dendritic Ca2+ spike, which significantly boosts dendritic inputs as it propagates to soma. Such event instantaneously shifts the limit cycle attractor of the neuron and results in a burst of APs, which makes its firing rate reach a plateau steady-state level. Delivering current to two chambers simultaneously increases the level of neuronal excitability and decreases the threshold of input-output relation. Here the back-propagating APs facilitate the initiation of dendritic Ca2+ spike and evoke BAC firing. These findings indicate that the proposed model is capable of reproducing in vitro experimental observations. By determining spike initiating dynamics, we have provided a fundamental link between dendritic Ca2+ spike and output APs, which could contribute to mechanically interpreting how dendritic Ca2+ activity participates in the simple computations of pyramidal neuron. PMID:28367964

  5. Networks of spiking neurons that compute linear functions using action potential timing

    NASA Astrophysics Data System (ADS)

    Ruf, Berthold

    1999-03-01

    For fast neural computations within the brain it is very likely that the timing of single firing events is relevant. Recently Maass has shown that under certain weak assumptions a weighted sum can be computed in temporal coding by leaky integrate-and-fire neurons. This construction can be extended to approximate arbitrary functions. In comparison to integrate-and-fire neurons there are several sources in biologically more realistic neurons for additional nonlinear effects like e.g. the spatial and temporal interaction of postsynaptic potentials or voltage-gated ion channels at the soma. Here we demonstrate with the help of computer simulations using GENESIS that despite of these nonlinearities such neurons can compute linear functions in a natural and straightforward way based on the main principles of the construction given by Maass. One only has to assume that a neuron receives all its inputs in a time interval of approximately the length of the rising segment of its excitatory postsynaptic potentials. We also show that under certain assumptions there exists within this construction some type of activation function being computed by such neurons. Finally we demonstrate that on the basis of these results it is possible to realize in a simple way pattern analysis with spiking neurons. It allows the analysis of a mixture of several learned patterns within a few milliseconds.

  6. 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.

  7. Branch specific and spike-order specific action potential invasion in basal, oblique, and apical dendrites of cortical pyramidal neurons

    PubMed Central

    Zhou, Wen-Liang; Short, Shaina M.; Rich, Matthew T.; Oikonomou, Katerina D.; Singh, Mandakini B.; Sterjanaj, Enas V.; Antic, Srdjan D.

    2014-01-01

    Abstract. In neocortical pyramidal neurons, action potentials (APs) propagate from the axon into the dendritic tree to influence distal synapses. Traditionally, AP backpropagation was studied in the thick apical trunk. Here, we used the principles of optical imaging developed by Cohen to investigate AP invasion into thin dendritic branches (basal, oblique, and tuft) of prefrontal cortical L5 pyramidal neurons. Multisite optical recordings from neighboring dendrites revealed a clear dichotomy between two seemingly equal dendritic branches belonging to the same cell (“sister branches”). We documented the variable efficacy of AP invasion in basal and oblique branches by revealing their AP voltage waveforms. Using fast multisite calcium imaging, we found that trains of APs are filtered differently between two apical tuft branches. Although one dendritic branch passes all spikes in an AP train, another branch belonging to the same neuron, same cortical layer, and same path distance from the cell body, experiences only one spike. Our data indicate that the vast differences in dendritic voltage and calcium transients, detected in dendrites of pyramidal neurons, arise from a nonuniform distribution of A-type K+ conductance, an aggregate number of branch points in the path of the AP propagation and minute differences in dendritic diameter. PMID:26157997

  8. Role of AMPA and NMDA receptors and back-propagating action potentials in spike timing-dependent plasticity.

    PubMed

    Fuenzalida, Marco; Fernández de Sevilla, David; Couve, Alejandro; Buño, Washington

    2010-01-01

    The cellular mechanisms that mediate spike timing-dependent plasticity (STDP) are largely unknown. We studied in vitro in CA1 pyramidal neurons the contribution of AMPA and N-methyl-d-aspartate (NMDA) components of Schaffer collateral (SC) excitatory postsynaptic potentials (EPSPs; EPSP(AMPA) and EPSP(NMDA)) and of the back-propagating action potential (BAP) to the long-term potentiation (LTP) induced by a STDP protocol that consisted in pairing an EPSP and a BAP. Transient blockade of EPSP(AMPA) with 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX) during the STDP protocol prevented LTP. Contrastingly LTP was induced under transient inhibition of EPSP(AMPA) by combining SC stimulation, an imposed EPSP(AMPA)-like depolarization, and BAP or by coupling the EPSP(NMDA) evoked under sustained depolarization (approximately -40 mV) and BAP. In Mg(2+)-free solution EPSP(NMDA) and BAP also produced LTP. Suppression of EPSP(NMDA) or BAP always prevented LTP. Thus activation of NMDA receptors and BAPs are needed but not sufficient because AMPA receptor activation is also obligatory for STDP. However, a transient depolarization of another origin that unblocks NMDA receptors and a BAP may also trigger LTP.

  9. Presynaptic spike broadening reduces junctional potential amplitude.

    PubMed

    Spencer, A N; Przysiezniak, J; Acosta-Urquidi, J; Basarsky, T A

    1989-08-24

    Presynaptic modulation of action potential duration may regulate synaptic transmission in both vertebrates and invertebrates. Such synaptic plasticity is brought about by modifications to membrane currents at presynaptic release sites, which, in turn, lead to changes in the concentration of cytosolic calcium available for mediating transmitter release. The 'primitive' neuromuscular junction of the jellyfish Polyorchis penicillatus is a useful model of presynaptic modulation. In this study, we show that the durations of action potentials in the motor neurons of this jellyfish are negatively correlated with the amplitude of excitatory junctional potentials. We present data from in vitro voltage-clamp experiments showing that short duration voltage spikes, which elicit large excitatory junctional potentials in vivo, produce larger and briefer calcium currents than do long duration action potentials, which elicit small excitatory junctional potentials.

  10. Relationships between spike-free local field potentials and spike timing in human temporal cortex

    PubMed Central

    Zanos, Theodoros P.; Marmarelis, Vasilis Z.; Ojemann, George A.; Fetz, Eberhard E.

    2012-01-01

    Intracortical recordings comprise both fast events, action potentials (APs), and slower events, known as local field potentials (LFPs). Although it is believed that LFPs mostly reflect local synaptic activity, it is unclear which of their signal components are most closely related to synaptic potentials and would therefore be causally related to the occurrence of individual APs. This issue is complicated by the significant contribution from AP waveforms, especially at higher LFP frequencies. In recordings of single-cell activity and LFPs from the human temporal cortex, we computed quantitative, nonlinear, causal dynamic models for the prediction of AP timing from LFPs, at millisecond resolution, before and after removing AP contributions to the LFP. In many cases, the timing of a significant number of single APs could be predicted from spike-free LFPs at different frequencies. Not surprisingly, model performance was superior when spikes were not removed. Cells whose activity was predicted by the spike-free LFP models generally fell into one of two groups: in the first group, neuronal spike activity was associated with specific phases of low LFP frequencies, lower spike activity at high LFP frequencies, and a stronger linear component in the spike-LFP model; in the second group, neuronal spike activity was associated with larger amplitude of high LFP frequencies, less frequent phase locking, and a stronger nonlinear model component. Spike timing in the first group was better predicted by the sign and level of the LFP preceding the spike, whereas spike timing in the second group was better predicted by LFP power during a certain time window before the spike. PMID:22157112

  11. BK and Kv3.1 potassium channels control different aspects of deep cerebellar nuclear neurons action potentials and spiking activity.

    PubMed

    Pedroarena, Christine M

    2011-12-01

    Deep cerebellar nuclear neurons (DCNs) display characteristic electrical properties, including spontaneous spiking and the ability to discharge narrow spikes at high frequency. These properties are thought to be relevant to processing inhibitory Purkinje cell input and transferring well-timed signals to cerebellar targets. Yet, the underlying ionic mechanisms are not completely understood. BK and Kv3.1 potassium channels subserve similar functions in spike repolarization and fast firing in many neurons and are both highly expressed in DCNs. Here, their role in the abovementioned spiking characteristics was addressed using whole-cell recordings of large and small putative-glutamatergic DCNs. Selective BK channel block depolarized DCNs of both groups and increased spontaneous firing rate but scarcely affected evoked activity. After adjusting the membrane potential to control levels, the spike waveforms under BK channel block were indistinguishable from control ones, indicating no significant BK channel involvement in spike repolarization. The increased firing rate suggests that lack of DCN-BK channels may have contributed to the ataxic phenotype previously found in BK channel-deficient mice. On the other hand, block of Kv3.1 channels with low doses of 4-aminopyridine (20 μM) hindered spike repolarization and severely depressed evoked fast firing. Therefore, I propose that despite similar characteristics of BK and Kv3.1 channels, they play different roles in DCNs: BK channels control almost exclusively spontaneous firing rate, whereas DCN-Kv3.1 channels dominate the spike repolarization and enable fast firing. Interestingly, after Kv3.1 channel block, BK channels gained a role in spike repolarization, demonstrating how the different function of each of the two channels is determined in part by their co-expression and interplay.

  12. Dopamine Modulates Spike Timing-Dependent Plasticity and Action Potential Properties in CA1 Pyramidal Neurons of Acute Rat Hippocampal Slices

    PubMed Central

    Edelmann, Elke; Lessmann, Volkmar

    2011-01-01

    Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15–20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10–20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons. PMID:22065958

  13. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

  14. Voltage-dependent membrane potential oscillations of rat striatal fast-spiking interneurons

    PubMed Central

    Bracci, Enrico; Centonze, Diego; Bernardi, Giorgio; Calabresi, Paolo

    2003-01-01

    We used whole-cell recordings to investigate subthreshold membrane potential oscillations and their relationship with intermittent firing in striatal fast-spiking interneurons. During current injections (100–500 pA, 1 s), these cells displayed a highly variable pattern of spike bursts (comprising 1–30 action potentials) interspersed with membrane potential oscillations. The oscillation threshold was −42 ± 10 mV, and coincided with that for action potentials. The oscillation frequency was voltage dependent and ranged between 20 and 100 Hz. Oscillations were unaffected by the calcium channel blockers cadmium and nickel and by blockers of ionotropic glutamate and GABA receptors. Conversely, the sodium channel blocker tetrodotoxin fully abolished the oscillations and the spike bursts. The first spike of a burst appeared to be triggered by an oscillation, since the timing and rate of rise of the membrane potential in the subthreshold voltage region was similar for the two events. Conversely, the second spike (and the subsequent ones) displayed much faster depolarisations in the subthreshold voltage range, indicating that they were generated by a different mechanism. Consistent with these notions, a small pulse of intracellular current delivered during the oscillation was effective in triggering a burst of action potentials that largely outlasted the pulse. We conclude that fast-spiking interneuron oscillations are generated by an intrinsic membrane mechanism that does not require fast synaptic transmission, and which depends on sodium conductance but not calcium conductance, and that such oscillations are responsible for triggering the intermittent spike bursts that are typical of these neurons. PMID:12665602

  15. Narrow and wide field amacrine cells fire action potentials in response to depolarization and light stimulation.

    PubMed

    Heflin, Stephanie J; Cook, Paul B

    2007-01-01

    Action potentials in amacrine cells are important for lateral propagation of signals across the inner retina, but it is unclear how many subclasses of amacrine cells contain voltage-gated sodium channels or can fire action potentials. This study investigated the ability of amacrine cells with narrow ( <200 microm) and wide (>200 microm) dendritic fields to fire action potentials in response to depolarizing current injections and light stimulation. The pattern of action potentials evoked by current injections revealed two distinct classes of amacrine cells; those that responded with a single action potential (single-spiking cells) and those that responded with repetitive action potentials (repetitive-spiking cells). Repetitive-spiking cells differed from single-spiking cells in several regards: Repetitive-spiking cells were more often wide field cells, while single-spiking cells were more often narrow field cells. Repetitive-spiking cells had larger action potential amplitudes, larger peak voltage-gated NaV currents lower action potential thresholds, and needed less current to induce action potentials. However, there was no difference in the input resistance, holding current or time constant of these two classes of cells. The intrinsic capacity to fire action potentials was mirrored in responses to light stimulation; single-spiking amacrine cells infrequently fired action potentials to light steps, while repetitive-spiking amacrine cells frequently fired numerous action potentials. These results indicate that there are two physiologically distinct classes of amacrine cells based on the intrinsic capacity to fire action potentials.

  16. 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.

  17. Sodium action potentials in the dendrites of cerebellar Purkinje cells.

    PubMed

    Regehr, W G; Konnerth, A; Armstrong, C M

    1992-06-15

    We report here that in cerebellar Purkinje cells from which the axon has been removed, positive voltage steps applied to the voltage-clamped soma produce spikes of active current. The spikes are inward, are all-or-none, have a duration of approximately 1 ms, and are reversibly eliminated by tetrodotoxin, a Na channel poison. From cell to cell, the amplitude of the spikes ranges from 4 to 20 nA. Spike latency decreases as the depolarizing step is made larger. These spikes clearly arise at a site where the voltage is not controlled, remote from the soma. From these facts we conclude that Purkinje cell dendrites contain a sufficient density of Na channels to generate action potentials. Activation by either parallel fiber or climbing fiber synapses produces similar spikes, suggesting that normal input elicits Na action potentials in the dendrites. These findings greatly alter current views of how dendrites in these cells respond to synaptic input.

  18. Hippocampal long-term potentiation is not accompanied by presynaptic spike broadening, unlike synaptic potentiation by K+ channel blockers.

    PubMed

    Laerum, H; Storm, J F

    1994-02-21

    The expression of hippocampal long-term potentiation (LTP) is thought to be at least partly due to increased transmitter release. To test whether this increase is due to a broadening of the presynaptic action potential, we have compared the presynaptic fibre volley before and after LTP induction, or application of K+ channel blockers, in CA1 of rat hippocampal slices. Tetraethylammonium (TEA; 1 mM) induced a parallel increase in the fibre volley duration of the slope of the field EPSP, indicating that a presynaptic spike broadening underlying synaptic potentiation can be detected. In contrast, induction of LTP did not produce any measurable change in the fibre volley, although the average increase in the EPSP slope was larger than with TEA. These results indicate that LTP expression is not primarily due to a presynaptic spike broadening.

  19. Measurement of the extraocular spike potential during saccade countermanding

    PubMed Central

    Godlove, David C.; Garr, Anna K.; Woodman, Geoffrey F.

    2011-01-01

    The stop signal task is used to investigate motor inhibition. Several groups have reported partial electromyogram (EMG) activation when subjects successfully withhold manual responses and have used this finding to define the nature of response inhibition properties in the spinal motor system. It is unknown whether subthreshold EMG activation from extraocular muscles can be detected in the saccadic response version of the stop signal task. The saccadic spike potential provides a way to examine extraocular EMG activation associated with eye movements in electroencephalogram (EEG) recordings. We used several techniques to isolate extraocular EMG activation from anterior electrode locations of EEG recorded from macaque monkeys. Robust EMG activation was present when eye movements were made, but no activation was detected when saccades were deemed canceled. This work highlights a key difference between the spinal motor system and the saccade system. PMID:21490279

  20. A high performing brain-machine interface driven by low-frequency local field potentials alone and together with spikes

    NASA Astrophysics Data System (ADS)

    Stavisky, Sergey D.; Kao, Jonathan C.; Nuyujukian, Paul; Ryu, Stephen I.; Shenoy, Krishna V.

    2015-06-01

    Objective. Brain-machine interfaces (BMIs) seek to enable people with movement disabilities to directly control prosthetic systems with their neural activity. Current high performance BMIs are driven by action potentials (spikes), but access to this signal often diminishes as sensors degrade over time. Decoding local field potentials (LFPs) as an alternative or complementary BMI control signal may improve performance when there is a paucity of spike signals. To date only a small handful of LFP decoding methods have been tested online; there remains a need to test different LFP decoding approaches and improve LFP-driven performance. There has also not been a reported demonstration of a hybrid BMI that decodes kinematics from both LFP and spikes. Here we first evaluate a BMI driven by the local motor potential (LMP), a low-pass filtered time-domain LFP amplitude feature. We then combine decoding of both LMP and spikes to implement a hybrid BMI. Approach. Spikes and LFP were recorded from two macaques implanted with multielectrode arrays in primary and premotor cortex while they performed a reaching task. We then evaluated closed-loop BMI control using biomimetic decoders driven by LMP, spikes, or both signals together. Main results. LMP decoding enabled quick and accurate cursor control which surpassed previously reported LFP BMI performance. Hybrid decoding of both spikes and LMP improved performance when spikes signal quality was mediocre to poor. Significance. These findings show that LMP is an effective BMI control signal which requires minimal power to extract and can substitute for or augment impoverished spikes signals. Use of this signal may lengthen the useful lifespan of BMIs and is therefore an important step towards clinically viable BMIs.

  1. A high performing brain-machine interface driven by low-frequency local field potentials alone and together with spikes

    PubMed Central

    Stavisky, Sergey D.; Kao, Jonathan C.; Nuyujukian, Paul; Ryu, Stephen I.; Shenoy, Krishna V.

    2015-01-01

    Objective Brain-machine interfaces (BMIs) seek to enable people with movement disabilities to directly control prosthetic systems with their neural activity. Current high performance BMIs are driven by action potentials (spikes), but access to this signal often diminishes as sensors degrade over time. Decoding local field potentials (LFPs) as an alternative or complementary BMI control signal may improve performance when there is a paucity of spike signals. To date only a small handful of LFP decoding methods have been tested online; there remains a need to test different LFP decoding approaches and improve LFP-driven performance. There has also not been a reported demonstration of a hybrid BMI that decodes kinematics from both LFP and spikes. Here we first evaluate a BMI driven by the local motor potential (LMP), a low-pass filtered time-domain LFP amplitude feature. We then combine decoding of both LMP and spikes to implement a hybrid BMI. Approach Spikes and LFP were recorded from two macaques implanted with multielectrode arrays in primary and premotor cortex while they performed a reaching task. We then evaluated closed-loop BMI control using biomimetic decoders driven by LMP, spikes, or both signals together. Main Results LMP decoding enabled quick and accurate cursor control which surpassed previously reported LFP BMI performance. Hybrid decoding of both spikes and LMP improved performance when spikes signal quality was mediocre to poor. Significance These findings show that LMP is an effective BMI control signal which requires minimal power to extract and can substitute for or augment impoverished spikes signals. Use of this signal may lengthen the useful lifespan of BMIs and is therefore an important step towards clinically viable BMIs. PMID:25946198

  2. Somatic membrane potential and Kv1 channels control spike repolarization in cortical axon collaterals and presynaptic boutons.

    PubMed

    Foust, Amanda J; Yu, Yuguo; Popovic, Marko; Zecevic, Dejan; McCormick, David A

    2011-10-26

    The shape of action potentials invading presynaptic terminals, which can vary significantly from spike waveforms recorded at the soma, may critically influence the probability of synaptic neurotransmitter release. Revealing the conductances that determine spike shape in presynaptic boutons is important for understanding how changes in the electrochemical context in which a spike is generated, such as subthreshold depolarization spreading from the soma, can modulate synaptic strength. Utilizing recent improvements in the signal-to-noise ratio of voltage-sensitive dye imaging in mouse brain slices, we demonstrate that intracortical axon collaterals and en passant presynaptic terminals of layer 5 pyramidal cells exhibit a high density of Kv1 subunit-containing ion channels, which generate a slowly inactivating K(+) current critically important for spike repolarization in these compartments. Blockade of the current by low doses of 4-aminopyridine or α-dendrotoxin dramatically slows the falling phase of action potentials in axon collaterals and presynaptic boutons. Furthermore, subthreshold depolarization of the soma broadened action potentials in collaterals bearing presynaptic boutons, an effect abolished by blocking Kv1 channels with α-dendrotoxin. These results indicate that action potential-induced synaptic transmission may operate through a mix of analog-digital transmission owing to the properties of Kv1 channels in axon collaterals and presynaptic boutons.

  3. Endocannabinoid dynamics gate spike-timing dependent depression and potentiation

    PubMed Central

    Cui, Yihui; Prokin, Ilya; Xu, Hao; Delord, Bruno; Genet, Stephane; Venance, Laurent; Berry, Hugues

    2016-01-01

    Synaptic plasticity is a cardinal cellular mechanism for learning and memory. The endocannabinoid (eCB) system has emerged as a pivotal pathway for synaptic plasticity because of its widely characterized ability to depress synaptic transmission on short- and long-term scales. Recent reports indicate that eCBs also mediate potentiation of the synapse. However, it is not known how eCB signaling may support bidirectionality. Here, we combined electrophysiology experiments with mathematical modeling to question the mechanisms of eCB bidirectionality in spike-timing dependent plasticity (STDP) at corticostriatal synapses. We demonstrate that STDP outcome is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Moreover, we show that eCB-tLTD requires active calcineurin whereas eCB-tLTP necessitates the activity of presynaptic PKA. Therefore, just like glutamate or GABA, eCB form a bidirectional system to encode learning and memory. DOI: http://dx.doi.org/10.7554/eLife.13185.001 PMID:26920222

  4. Estimating the correlation between bursty spike trains and local field potentials.

    PubMed

    Li, Zhaohui; Ouyang, Gaoxiang; Yao, Li; Li, Xiaoli

    2014-09-01

    To further understand rhythmic neuronal synchronization, an increasingly useful method is to determine the relationship between the spiking activity of individual neurons and the local field potentials (LFPs) of neural ensembles. Spike field coherence (SFC) is a widely used method for measuring the synchronization between spike trains and LFPs. However, due to the strong dependency of SFC on the burst index, it is not suitable for analyzing the relationship between bursty spike trains and LFPs, particularly in high frequency bands. To address this issue, we developed a method called weighted spike field correlation (WSFC), which uses the first spike in each burst multiple times to estimate the relationship. In the calculation, the number of times that the first spike is used is equal to the spike count per burst. The performance of this method was demonstrated using simulated bursty spike trains and LFPs, which comprised sinusoids with different frequencies, amplitudes, and phases. This method was also used to estimate the correlation between pyramidal cells in the hippocampus and gamma oscillations in rats performing behaviors. Analyses using simulated and real data demonstrated that the WSFC method is a promising measure for estimating the correlation between bursty spike trains and high frequency LFPs.

  5. Warm body temperature facilitates energy efficient cortical action potentials.

    PubMed

    Yu, Yuguo; Hill, Adam P; McCormick, David A

    2012-01-01

    The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na(+) channel inactivation, resulting in a marked reduction in overlap of the inward Na(+), and outward K(+), currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na(+) entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37-42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code.

  6. Action potential broadening in a presynaptic channelopathy

    PubMed Central

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

    2016-01-01

    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. PMID:27381274

  7. 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.

  8. Action potential broadening in a presynaptic channelopathy.

    PubMed

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

    2016-07-06

    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 Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  9. Model-based source localization of extracellular action potentials.

    PubMed

    Somogyvári, Zoltán; Zalányi, László; Ulbert, István; Erdi, Péter

    2005-09-30

    A new model-based analysis method was set up for revealing information encrypted in extracellular spatial potential patterns of neocortical action potentials. Spikes were measured by extracellular linear multiple microelectrode in vivo cat's primary auditory cortex and were analyzed based on current source density (CSD) distribution models. Validity of the monopole and other point source approximations were tested on the measured potential patterns by numerical fitting. We have found, that point source models could not provide accurate description of the measured patterns. We introduced a new model of the CSD distribution on a spiking cell, called counter-current model (CCM). This new model was shown to provide better description of the spatial current distribution of the cell during the initial negative deflection of the extracellular action potential, from the onset of the spike to the negative peak. The new model was tested on simulated extracellular potentials. We proved numerically, that all the parameters of the model could be determined accurately based on measurements. Thus, fitting of the CCM allowed extraction of these parameters from the measurements. Due to model fitting, CSD could be calculated with much higher accuracy as done with the traditional method because distance dependence of the spatial potential patterns was explicitly taken into consideration in our method. Average CSD distribution of the neocortical action potentials was calculated and spatial decay constant of the dendritic trees was determined by applying our new method.

  10. Subthreshold Membrane-Potential Resonances Shape Spike-Train Patterns in the Entorhinal Cortex

    PubMed Central

    Engel, T. A.; Schimansky-Geier, L.; Herz, A.V.M.; Schreiber, S.; Erchova, I.

    2008-01-01

    Many neurons exhibit subthreshold membrane-potential resonances, such that the largest voltage responses occur at preferred stimulation frequencies. Because subthreshold resonances are known to influence the rhythmic activity at the network level, it is vital to understand how they affect spike generation on the single-cell level. We therefore investigated both resonant and nonresonant neurons of rat entorhinal cortex. A minimal resonate-and-fire type model based on measured physiological parameters captures fundamental properties of neuronal firing statistics surprisingly well and helps to shed light on the mechanisms that shape spike patterns: 1) subthreshold resonance together with a spike-induced reset of subthreshold oscillations leads to spike clustering and 2) spike-induced dynamics influence the fine structure of interspike interval (ISI) distributions and are responsible for ISI correlations appearing at higher firing rates (≥3 Hz). Both mechanisms are likely to account for the specific discharge characteristics of various cell types. PMID:18450582

  11. EPSP-spike potentiation during primed burst-induced long-term potentiation in the CA1 region of rat hippocampal slices.

    PubMed

    Pugliese, A M; Ballerini, L; Passani, M B; Corradetti, R

    1994-10-01

    Long-term potentiation induced by high-frequency stimulation in the CA1 region of the hippocampus exhibits EPSP-spike potentiation. This consists of an increase in population spike amplitude exceeding that predicted by EPSP potentiation alone. This phenomenon is apparently due to an increase in pyramidal cell excitability. Patterns of afferent stimuli which activate pyramidal cells to reproduce the theta rhythm observed in the hippocampus under physiological conditions, have been shown to induce LTP-like enhancement of synaptic responses in vitro. The aim of this study was to investigate the presence of EPSP-spike potentiation and/or changes in pyramidal cell excitability during the long-term potentiation induced in the CA1 region of rat hippocampal slices by theta-like patterns of stimuli: the primed burst and the patterned stimulation. Using extracellular recording, a significant leftward shift in the EPSP-spike relationship was found 30 min after primed burst or patterned stimulation. The magnitude of EPSP-spike potentiation induced by patterned stimulation was similar to that produced by high-frequency stimulation. Both were significantly greater than that induced by a primed burst, indicating that only a subset of pyramidal cells were potentiated by this kind of afferent activation. Modifications in synaptic efficacy and cell excitability brought about by a primed burst were investigated in 25 intracellularly recorded pyramidal cells. Consistent with extracellular results, it was found that only 11 out of 25 neurons receiving a primed burst were potentiated. In these cells the increase in probability of firing action potentials elicited by synaptic activation with test shocks was accompanied by enhanced cell excitability, but not by an increase in EPSP slope. High-frequency stimulation delivered 40 min after a primed burst invariably increased the EPSP slope, the probability of firing upon synaptic stimulation, and the excitability of cells. The presence of

  12. Components of action potential repolarization in cerebellar parallel fibres

    PubMed Central

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

    2014-01-01

    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. PMID:25239461

  13. 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

  14. Primary cortical representation of sounds by the coordination of action-potential timing.

    PubMed

    deCharms, R C; Merzenich, M M

    1996-06-13

    Cortical population coding could in principle rely on either the mean rate of neuronal action potentials, or the relative timing of action potentials, or both. When a single sensory stimulus drives many neurons to fire at elevated rates, the spikes of these neurons become tightly synchronized, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept. Here we demonstrate that the relative timing of cortical action potentials can signal stimulus features themselves, a function even more basic than feature grouping. Populations of neurons in the primary auditory cortex can coordinate the relative timing of their action potentials such that spikes occur closer together in time during continuous stimuli. In this way cortical neurons can signal stimuli even when their firing rates do not change. Population coding based on relative spike timing can systemically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

  15. Spike Ca2+ influx upmodulates the spike afterdepolarization and bursting via intracellular inhibition of KV7/M channels

    PubMed Central

    Chen, Shmuel; Yaari, Yoel

    2008-01-01

    In principal brain neurons, activation of Ca2+ channels during an action potential, or spike, causes Ca2+ entry into the cytosol within a millisecond. This in turn causes rapid activation of large conductance Ca2+-gated channels, which enhances repolarization and abbreviates the spike. Here we describe another remarkable consequence of spike Ca2+ entry: enhancement of the spike afterdepolarization. This action is also mediated by intracellular modulation of a particular class of K+ channels, namely by inhibition of KV7 (KCNQ) channels. These channels generate the subthreshold, non-inactivating M-type K+ current, whose activation curtails the spike afterdepolarization. Inhibition of KV7/M by spike Ca2+ entry allows the spike afterdepolarization to grow and can convert solitary spikes into high-frequency bursts of action potentials. Through this novel intracellular modulatory action, Ca2+ spike entry regulates the discharge mode and the signalling capacity of principal brain neurons. PMID:18187471

  16. Slow and Spike Potentials Recorded from Retinula Cells of the Honeybee Drone in Response to Light

    PubMed Central

    Baumann, Fritz

    1968-01-01

    Responses to light recorded by means of intracellular microelectrodes in isolated heads kept in oxygenated Ringer solution consist of a slow depolarization. Light adaptation increases the rates of depolarization and repolarization and decreases the amplitude of the response. Qualitatively these changes are similar to those observed in Limulus by Fuortes and Hodgkin. They are rapidly reversible during dark adaptation. In retinula cells of the drone eye a large single spike is recorded superimposed on the rising phase of the slow potential. The spike is a regenerative phenomenon; it can be triggered with electric current and is markedly reduced, sometimes abolished by tetrodotoxin. In rare cases cells were found which responded to light with a train of spikes. This behavior was only found under "unusual" experimental conditions; i.e., towards the end of a long experiment, during impalement, or at the beginning of responses to steps of strongly light-adapted preparations. PMID:5722083

  17. Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats.

    PubMed

    Truchet, Bruno; Manrique, Christine; Sreng, Leam; Chaillan, Franck A; Roman, François S; Mourre, Christiane

    2012-06-14

    Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and stabilized the EPSP-spike (E-S) component of LTP in the dentate gyrus (DG), with no effect on basal transmission or short-term plasticity. This increase in E-S potentiation duration could result from the combination of an increase in excitability of DG granular cells with a reduction of GABAergic inhibition, leading to a strong reduction of input specificity. Radioactive in situ hybridization (ISH) was used to evaluate the amounts of Kv4.2 and Kv4.3 mRNA in brain structures at different stages of a spatial learning task in naive, pseudoconditioned, and conditioned rats. Significant differences in Kv4.2 and Kv4.3 mRNA levels were observed between conditioned and pseudoconditioned rats. Kv4.2 and Kv4.3 mRNA levels were transiently up-regulated in the striatum, nucleus accumbens, retrosplenial, and cingulate cortices during early stages of learning, suggesting an involvement in the switch from egocentric to allocentric strategies. Spatial learning performance was positively correlated with the levels of Kv4.2 and Kv4.3 mRNAs in several of these brain structures. Altogether our findings suggest that Kv4 channels could increase the signal-to-noise ratio during information acquisition, thereby allowing a better encoding of the memory trace.

  18. The spiking component of oscillatory extracellular potentials in the rat hippocampus

    PubMed Central

    Schomburg, Erik W.; Anastassiou, Costas A.; Buzsáki, György; Koch, Christof

    2012-01-01

    When monitoring neural activity using intracranial electrical recordings, researchers typically consider the signals to have two primary components: fast action potentials (AP) from neurons near the electrode, and the slower local field potential (LFP), thought to be dominated by postsynaptic currents integrated over a larger volume of tissue. In general, a decrease in signal power with increasing frequency is observed for most brain rhythms. 100–200 Hz oscillations in the rat hippocampus, including ‘fast gamma’ or ‘epsilon’ oscillations and sharp wave-ripples (SPW-R), are one exception, showing an increase in power with frequency within this band. We have employed detailed biophysical modeling to investigate the composition of extracellular potentials during fast oscillations in rat CA1. We find that postsynaptic currents exhibit a decreasing ability to generate large amplitude oscillatory signals at high frequencies, whereas phase-modulated spiking shows the opposite trend. Our estimates indicate that APs and postsynaptic currents contribute similar proportions of the power contained in 140–200 Hz ripples, and the two combined generate a signal that closely resembles in vivo SPW-Rs. Much of the AP-generated signal originates from neurons further than 100 μm from the recording site, consistent with ripples appearing similarly strong regardless of whether or not they contain recognizable APs. Additionally, substantial power can be generated in the 90–150 Hz epsilon band by the APs from rhythmically firing pyramidal neurons. Thus, high frequency LFPs may generally contain signatures of local cell assembly activation. PMID:22915121

  19. Spike-timing-dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition.

    PubMed

    Gambino, Frédéric; Holtmaat, Anthony

    2012-08-09

    Functional maps in the cerebral cortex reorganize in response to changes in experience, but the synaptic underpinnings remain uncertain. Here, we demonstrate that layer (L) 2/3 pyramidal cell synapses in mouse barrel cortex can be potentiated upon pairing of whisker-evoked postsynaptic potentials (PSPs) with action potentials (APs). This spike-timing-dependent long-term potentiation (STD-LTP) was only effective for PSPs evoked by deflections of a whisker in the neuron's receptive field center, and not its surround. Trimming of all except two whiskers rapidly opened the possibility to drive STD-LTP by the spared surround whisker. This facilitated STD-LTP was associated with a strong decrease in the surrounding whisker-evoked inhibitory conductance and partially occluded picrotoxin-mediated LTP facilitation. Taken together, our data demonstrate that sensory deprivation-mediated disinhibition facilitates STD-LTP from the sensory surround, which may promote correlation- and experience-dependent expansion of receptive fields.

  20. Generation of spatiotemporally correlated spike trains and local field potentials using a multivariate autoregressive process.

    PubMed

    Gutnisky, Diego A; Josić, Kresimir

    2010-05-01

    Experimental advances allowing for the simultaneous recording of activity at multiple sites have significantly increased our understanding of the spatiotemporal patterns in neural activity. The impact of such patterns on neural coding is a fundamental question in neuroscience. The simulation of spike trains with predetermined activity patterns is therefore an important ingredient in the study of potential neural codes. Such artificially generated spike trains could also be used to manipulate cortical neurons in vitro and in vivo. Here, we propose a method to generate spike trains with given mean firing rates and cross-correlations. To capture this statistical structure we generate a point process by thresholding a stochastic process that is continuous in space and discrete in time. This stochastic process is obtained by filtering Gaussian noise through a multivariate autoregressive (AR) model. The parameters of the AR model are obtained by a nonlinear transformation of the point-process correlations to the continuous-process correlations. The proposed method is very efficient and allows for the simulation of large neural populations. It can be optimized to the structure of spatiotemporal correlations and generalized to nonstationary processes and spatiotemporal patterns of local field potentials and spike trains.

  1. Action potential shape change in an electrically coupled network during propagation: a computer simulation.

    PubMed

    Buckingham, Steven D; Spencer, Andrew N

    2008-06-01

    We applied compartmental computer modeling to test a model of spike shape change in the jellyfish, Polyorchis penicillatus, to determine whether adaptive spike shortening can be attributed to the inactivation properties of a potassium channel. We modeled the jellyfish outer nerve-ring as a continuous linear segment, using ion channel and membrane properties derived in earlier studies. The model supported action potentials that shortened as they propagated away from the site of initiation and this was found to be largely independent of potassium channel inactivation. Spike broadening near the site of initiation was found to be due to a depolarization plateau that collapsed as two spikes spread from the point of initiation. The lifetime of this plateau was found to depend critically on the inward current flux and the space constant of the membrane. These data suggest that the spike shape changes may be due not only to potassium channel inactivation, but also to the passive properties of the membrane.

  2. Activity dependence of action potential duration in rat supraoptic neurosecretory neurones recorded in vitro.

    PubMed

    Bourque, C W; Renaud, L P

    1985-06-01

    Action potential durations, measured at one-third peak amplitude, were examined during intracellular recordings in 134 supraoptic nucleus neurones maintained in vitro in perfused hypothalamic explants. Spike durations ranged between 1.2 and 3.9 ms and were dependent on firing frequency. Shortest measurements (1.74 +/- 0.03 ms; mean +/- S.E. of mean) were obtained during relative quiescence, i.e. less than or equal to 0.5 Hz. A gradual increase in firing frequency through continuous injection of depolarizing current prolonged spike duration, with maximum levels (2.68 +/- 0.05 ms) achieved at 20 Hz. When interspike interval variability was eliminated and firing was more precisely regulated by brief 15-20 ms intracellular current pulses given at pre-determined frequencies, a proportional relationship between increasing spike duration and firing frequency was retained but the change in spike duration at frequencies between 2 and 10 Hz was less pronounced. Once action potentials had achieved the long duration configuration, their return to the shorter duration took place gradually during any succeeding silent interval with a time constant of 4.9 s. Action potential broadening occurred progressively and was most pronounced at the onset of spontaneous or current-induced bursts. In thirty-six phasically active neurones, spike broadening at the onset of a burst was concurrent with the presence of 5-10 consecutive short (less than or equal to 100 ms) interspike intervals; thereafter, despite a greater than 50% reduction in firing frequency, action potential durations remained prolonged throughout the burst. In all of nineteen cells tested, frequency-dependent changes in spike duration were reversibly decreased or blocked by Cd2+, Co2+ and Mn2+, or when CaCl2 was exchanged for equimolar amounts of EGTA in the perfusion medium. These observations indicate that a Ca2+ conductance contributes to frequency- and firing-pattern-dependent changes in spike duration in rat supraoptic

  3. Development of action potentials and apamin-sensitive after-potentials in mouse vestibular nucleus neurones.

    PubMed

    Dutia, M B; Johnston, A R

    1998-01-01

    The postnatal maturation of medial vestibular nucleus (MVN) neurones was examined in slices of the dorsal brainstem prepared from balb/c mice at specific stages during the first postnatal month. Using spike-shape averaging to analyse the intracellularly recorded action potentials and after-hyperpolarizations (AHPs) in each cell, all the MVN neurones recorded in the young adult (postnatal day 30; P30) mouse were shown to have either a single deep AHP (type A cells), or an early fast and a delayed slow AHP (type B cells). The relative proportions of the two subtypes were similar to those in the young adult rat. At P5, all the MVN cells recorded showed immature forms of either the type A or the type B action potential shape. Immature type A cells had broad spontaneous spikes, and the characteristic single AHP was small in amplitude. Immature type B cells had somewhat narrower spontaneous spikes that were followed by a delayed, apamin-sensitive AHP. The delayed AHP was separated from the repolarisation phase of the spike by a period of isopotentiality. Over the period P10-P15, the mean resting potentials of the MVN cells became more negative, their action potential fall-times became shorter, the single AHP in type A cells became deeper, and the early fast AHP appeared in type B cells. Until P15 cells of varying degrees of electrophysiological maturity were found in the MVN but by P30 all MVN cells recorded were typical adult type A or type B cells. Exposure to the selective blocker of SK-type Ca-activated K channels, apamin (0.3 microM), induced depolarising plateaux and burst firing in immature type B cells at rest. The duration of the apamin-induced bursts and the spike frequency during the bursts were reduced but not abolished after blockade of Ca channels in Ca-free artificial cerebrospinal fluid containing Cd2+. By contrast, in mature type B cells at rest apamin selectively abolished the delayed slow AHP but did not induce bursting activity. Apamin had no effect

  4. Spike-timing control by dendritic plateau potentials in the presence of synaptic barrages

    PubMed Central

    Shai, Adam S.; Koch, Christof; Anastassiou, Costas A.

    2014-01-01

    Apical and tuft dendrites of pyramidal neurons support regenerative electrical potentials, giving rise to long-lasting (approximately hundreds of milliseconds) and strong (~50 mV from rest) depolarizations. Such plateau events rely on clustered glutamatergic input, can be mediated by calcium or by NMDA currents, and often generate somatic depolarizations that last for the time course of the dendritic plateau event. We address the computational significance of such single-neuron processing via reduced but biophysically realistic modeling. We introduce a model based on two discrete integration zones, a somatic and a dendritic one, that communicate from the dendritic to the somatic compartment via a long plateau-conductance. We show principled differences in the way dendritic vs. somatic inhibition controls spike timing, and demonstrate how this could implement spike time control in the face of barrages of synaptic inputs. PMID:25177288

  5. Separation of synaptic and spike activity in intracellular recordings for selective analysis.

    PubMed

    Hedwig, B; Knepper, M

    1992-04-01

    A software spike filter has been developed which allows the separation of synaptic activity and action potentials in intracellular recordings. The algorithm uses the different velocities of the membrane potential during synaptic and spike activity and a time window to identify action potentials. When spikes are recognized, they are removed and the membrane potential is substituted by interpolated values. The spike filter makes possible a separate quantitative evaluation of postsynaptic potentials and spike activity. Thus a comprehensive characterization of neuron activity can be obtained. The spike filter is part of a modular software package designed for the evaluation of neurobiological data.

  6. Action potential fidelity during normal and epileptiform activity in paired soma-axon recordings from rat hippocampus.

    PubMed

    Meeks, Julian P; Jiang, Xiaoping; Mennerick, Steven

    2005-07-15

    Although action potential initiation and propagation are fundamental to nervous system function, there are few direct electrophysiological observations of propagating action potentials in small unmyelinated fibres, such as the axons within mammalian hippocampus. To circumvent limitations of previous studies that relied on extracellular stimulation, we performed dual recordings: whole-cell recordings from hippocampal CA3 pyramidal cell somas and extracellular recordings from their axons, up to 800 micro m away. During brief spike trains under normal conditions, axonal spikes were more resistant to amplitude reduction than somatic spikes. Axonal amplitude depression was greatest at the axon initial segment < 150 microm from the soma, and initiation occurred approximately 75 microm from the soma. Although prior studies, which failed to verify spike initiation, suggested substantial axonal depression during seizure-associated extracellular K+([K+]o) rises, we found that 8 mm [K+]o caused relatively small decreases in axonal spike amplitude during brief spike trains. However, during sustained, epileptiform spiking induced in 8 mm [K+]o, axonal waveforms decreased significantly in peak amplitude. During epileptiform spiking, bursts of two or more action potentials > 20 Hz failed to propagate in most cases. In normal [K+]o at 25 and 32 degrees C, spiking superimposed on sustained somatic depolarization, but not spiking alone, produced similar axonal changes as the epileptiform activity. These results highlight the likely importance of steady-state inactivation of axonal channels in maintaining action potential fidelity. Such changes in axonal propagation properties could encode information and/or serve as an endogenous brake on seizure propagation.

  7. The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes

    PubMed Central

    Burroughs, Amelia; Wise, Andrew K.; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y.; Lang, Eric J.

    2016-01-01

    Key points Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes.Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets.The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear.We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number.This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Abstract Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake

  8. Simulation of action potential propagation in plants.

    PubMed

    Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

    2011-12-21

    Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity.

  9. Long term, stable brain machine interface performance using local field potentials and multiunit spikes

    NASA Astrophysics Data System (ADS)

    Flint, Robert D.; Wright, Zachary A.; Scheid, Michael R.; Slutzky, Marc W.

    2013-10-01

    Objective. Brain machine interfaces (BMIs) have the potential to restore movement to people with paralysis. However, a clinically-viable BMI must enable consistently accurate control over time spans ranging from years to decades, which has not yet been demonstrated. Most BMIs that use single-unit spikes as inputs will experience degraded performance over time without frequent decoder re-training. Two other signals, local field potentials (LFPs) and multi-unit spikes (MSPs), may offer greater reliability over long periods and better performance stability than single-unit spikes. Here, we demonstrate that LFPs can be used in a biomimetic BMI to control a computer cursor. Approach. We implanted two rhesus macaques with intracortical microelectrodes in primary motor cortex. We recorded LFP and MSP signals from the monkeys while they performed a continuous reaching task, moving a cursor to randomly-placed targets on a computer screen. We then used the LFP and MSP signals to construct biomimetic decoders for control of the cursor. Main results. Both monkeys achieved high-performance, continuous control that remained stable or improved over nearly 12 months using an LFP decoder that was not retrained or adapted. In parallel, the monkeys used MSPs to control a BMI without retraining or adaptation and had similar or better performance, and that predominantly remained stable over more than six months. In contrast to their stable online control, both LFP and MSP signals showed substantial variability when used offline to predict hand movements. Significance. Our results suggest that the monkeys were able to stabilize the relationship between neural activity and cursor movement during online BMI control, despite variability in the relationship between neural activity and hand movements.

  10. Imaging action potentials with calcium indicators.

    PubMed

    MacLean, Jason N; Yuste, Rafael

    2009-11-01

    The understanding of neuronal circuits has been, and will continue to be, greatly advanced by the simultaneous imaging of action potentials in neuronal ensembles. This protocol describes "bulk" loading of brain slices with acetoxymethyl (AM) ester calcium indicators in order to monitor action potential activity in large populations of neurons simultaneously. The imaging of calcium influx into neurons provides an indirect, but accurate, measure of action potential generation in individual neurons. Single-cell resolution, and thus the easy identification of every active cell, is the key advantage of the technique.

  11. Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

    PubMed Central

    Kim, Yujin; Hsu, Ching-Lung; Cembrowski, Mark S; Mensh, Brett D; Spruston, Nelson

    2015-01-01

    Dendritic integration of synaptic inputs mediates rapid neural computation as well as longer-lasting plasticity. Several channel types can mediate dendritically initiated spikes (dSpikes), which may impact information processing and storage across multiple timescales; however, the roles of different channels in the rapid vs long-term effects of dSpikes are unknown. We show here that dSpikes mediated by Nav channels (blocked by a low concentration of TTX) are required for long-term potentiation (LTP) in the distal apical dendrites of hippocampal pyramidal neurons. Furthermore, imaging, simulations, and buffering experiments all support a model whereby fast Nav channel-mediated dSpikes (Na-dSpikes) contribute to LTP induction by promoting large, transient, localized increases in intracellular calcium concentration near the calcium-conducting pores of NMDAR and L-type Cav channels. Thus, in addition to contributing to rapid neural processing, Na-dSpikes are likely to contribute to memory formation via their role in long-lasting synaptic plasticity. DOI: http://dx.doi.org/10.7554/eLife.06414.001 PMID:26247712

  12. Spiking irregularity and frequency modulate the behavioral report of single-neuron stimulation.

    PubMed

    Doron, Guy; von Heimendahl, Moritz; Schlattmann, Peter; Houweling, Arthur R; Brecht, Michael

    2014-02-05

    The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning.

  13. Kv4 Potassium Channels Modulate Hippocampal EPSP-Spike Potentiation and Spatial Memory in Rats

    ERIC Educational Resources Information Center

    Truchet, Bruno; Manrique, Christine; Sreng, Leam; Chaillan, Franck A.; Roman, Francois S.; Mourre, Christiane

    2012-01-01

    Kv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of long-term potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and…

  14. Graded Synaptic Transmission between Spiking Neurons

    NASA Astrophysics Data System (ADS)

    Graubard, Katherine; Raper, Jonathan A.; Hartline, Daniel K.

    1980-06-01

    Graded synaptic transmission occurs between spiking neurons of the lobster stomatogastric ganglion. In addition to eliciting spike-evoked inhibitory potentials in postsynaptic cells, these neurons also release functionally significant amounts of transmitter below the threshold for action potentials. The spikeless postsynaptic potentials grade in amplitude with presynaptic voltage and can be maintained for long periods. Graded synaptic transmission can be modulated by synaptic input to the presynaptic neuron.

  15. A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation

    PubMed Central

    Fiebig, Florian

    2017-01-01

    A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. SIGNIFICANCE STATEMENT Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and

  16. A spiking neuron model of the cortico-basal ganglia circuits for goal-directed and habitual action learning.

    PubMed

    Chersi, Fabian; Mirolli, Marco; Pezzulo, Giovanni; Baldassarre, Gianluca

    2013-05-01

    Dual-system theories postulate that actions are supported either by a goal-directed or by a habit-driven response system. Neuroimaging and anatomo-functional studies have provided evidence that the prefrontal cortex plays a fundamental role in the first type of action control, while internal brain areas such as the basal ganglia are more active during habitual and overtrained responses. Additionally, it has been shown that areas of the cortex and the basal ganglia are connected through multiple parallel "channels", which are thought to function as an action selection mechanism resolving competitions between alternative options available in a given context. In this paper we propose a multi-layer network of spiking neurons that implements in detail the thalamo-cortical circuits that are believed to be involved in action learning and execution. A key feature of this model is that neurons are organized in small pools in the motor cortex and form independent loops with specific pools of the basal ganglia where inhibitory circuits implement a multistep selection mechanism. The described model has been validated utilizing it to control the actions of a virtual monkey that has to learn to turn on briefly flashing lights by pressing corresponding buttons on a board. When the animal is able to fluently execute the task the button-light associations are remapped so that it has to suppress its habitual behavior in order to execute goal-directed actions. The model nicely shows how sensory-motor associations for action sequences are formed at the cortico-basal ganglia level and how goal-directed decisions may override automatic motor responses.

  17. Serial Spike Time Correlations Affect Probability Distribution of Joint Spike Events

    PubMed Central

    Shahi, Mina; van Vreeswijk, Carl; Pipa, Gordon

    2016-01-01

    Detecting the existence of temporally coordinated spiking activity, and its role in information processing in the cortex, has remained a major challenge for neuroscience research. Different methods and approaches have been suggested to test whether the observed synchronized events are significantly different from those expected by chance. To analyze the simultaneous spike trains for precise spike correlation, these methods typically model the spike trains as a Poisson process implying that the generation of each spike is independent of all the other spikes. However, studies have shown that neural spike trains exhibit dependence among spike sequences, such as the absolute and relative refractory periods which govern the spike probability of the oncoming action potential based on the time of the last spike, or the bursting behavior, which is characterized by short epochs of rapid action potentials, followed by longer episodes of silence. Here we investigate non-renewal processes with the inter-spike interval distribution model that incorporates spike-history dependence of individual neurons. For that, we use the Monte Carlo method to estimate the full shape of the coincidence count distribution and to generate false positives for coincidence detection. The results show that compared to the distributions based on homogeneous Poisson processes, and also non-Poisson processes, the width of the distribution of joint spike events changes. Non-renewal processes can lead to both heavy tailed or narrow coincidence distribution. We conclude that small differences in the exact autostructure of the point process can cause large differences in the width of a coincidence distribution. Therefore, manipulations of the autostructure for the estimation of significance of joint spike events seem to be inadequate. PMID:28066225

  18. Serial Spike Time Correlations Affect Probability Distribution of Joint Spike Events.

    PubMed

    Shahi, Mina; van Vreeswijk, Carl; Pipa, Gordon

    2016-01-01

    Detecting the existence of temporally coordinated spiking activity, and its role in information processing in the cortex, has remained a major challenge for neuroscience research. Different methods and approaches have been suggested to test whether the observed synchronized events are significantly different from those expected by chance. To analyze the simultaneous spike trains for precise spike correlation, these methods typically model the spike trains as a Poisson process implying that the generation of each spike is independent of all the other spikes. However, studies have shown that neural spike trains exhibit dependence among spike sequences, such as the absolute and relative refractory periods which govern the spike probability of the oncoming action potential based on the time of the last spike, or the bursting behavior, which is characterized by short epochs of rapid action potentials, followed by longer episodes of silence. Here we investigate non-renewal processes with the inter-spike interval distribution model that incorporates spike-history dependence of individual neurons. For that, we use the Monte Carlo method to estimate the full shape of the coincidence count distribution and to generate false positives for coincidence detection. The results show that compared to the distributions based on homogeneous Poisson processes, and also non-Poisson processes, the width of the distribution of joint spike events changes. Non-renewal processes can lead to both heavy tailed or narrow coincidence distribution. We conclude that small differences in the exact autostructure of the point process can cause large differences in the width of a coincidence distribution. Therefore, manipulations of the autostructure for the estimation of significance of joint spike events seem to be inadequate.

  19. Computer Simulation of the Neuronal Action Potential.

    ERIC Educational Resources Information Center

    Solomon, Paul R.; And Others

    1988-01-01

    A series of computer simulations of the neuronal resting and action potentials are described. Discusses the use of simulations to overcome the difficulties of traditional instruction, such as blackboard illustration, which can only illustrate these events at one point in time. Describes systems requirements necessary to run the simulations.…

  20. Introducing the Action Potential to Psychology Students

    ERIC Educational Resources Information Center

    Simon-Dack, Stephanie L.

    2014-01-01

    For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

  1. Neuronal adaptation involves rapid expansion of the action potential initiation site

    PubMed Central

    Scott, Ricardo S.; Henneberger, Christian; Padmashri, Ragunathan; Anders, Stefanie; Jensen, Thomas P.; Rusakov, Dmitri A.

    2014-01-01

    Action potential (AP) generation is the key to information-processing in the brain. Although APs are normally initiated in the axonal initial segment, developmental adaptation or prolonged network activity may alter the initiation site geometry thus affecting cell excitability. Here we find that hippocampal dentate granule cells adapt their spiking threshold to the kinetics of the ongoing dendrosomatic excitatory input by expanding the AP-initiation area away from the soma while also decelerating local axonal spikes. Dual-patch soma–axon recordings combined with axonal Na+ and Ca2+ imaging and biophysical modelling show that the underlying mechanism involves distance-dependent inactivation of axonal Na+ channels due to somatic depolarization propagating into the axon. Thus, the ensuing changes in the AP-initiation zone and local AP propagation could provide activity-dependent control of cell excitability and spiking on a relatively rapid timescale. PMID:24851940

  2. A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation.

    PubMed

    Fiebig, Florian; Lansner, Anders

    2017-01-04

    A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism.

  3. FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon

    PubMed Central

    Dover, Katarzyna; Marra, Christopher; Solinas, Sergio; Popovic, Marko; Subramaniyam, Sathyaa; Zecevic, Dejan; D'Angelo, Egidio; Goldfarb, Mitchell

    2016-01-01

    Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as <1% that of somatodendritic membrane. The faster inactivation rate of FHF-free Navs together with very low axonal leak conductance serves to minimize ionic fluxes and energetic demand during repetitive spike conduction and at rest. The absence of FHFs from Navs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons. PMID:27666389

  4. The action potential of Dionaea muscipula Ellis.

    PubMed

    Hodick, D; Sievers, A

    1988-04-01

    The intention of this investigation was to acquire more concise information about the nature of the action potential of Dionaea muscipula Ellis and the different types of cells generating and conducting it. It is shown by microelectrode measurements that, besides the sensory cells, all the major tissues of the trap lobes are excitable, firing action potentials with pronounced after-hyperpolarizations. The action potentials are strictly dependent on Ca(2+). Their peak depolarizations are shifted 25-27 mV in a positive direction after a tenfold increase in external Ca(2+) concentration. Perfusions with 1 mM ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) or 1 mM LaCl3 completely inhibit excitability. Magnesium ions only slightly affect the peak depolarizations but considerably prolong action potentials. Sodium azide and 2,4-dinitrophenol also abolish excitation, probably by reducing the intracellular ATP concentration. Furthermore, it is tested whether the sensory cells can be distinguished from the other cells of the trap by their electrical behaviour. The resting potentials of sensory cells (-161±7 mV) and mesophyll cells (-155±8 mV) are of the same magnitude. Changes in external ion concentrations affect resting and action potentials in both cell types in a similar way. Additional freeze-fracture studies of both cell types reveal similar numbers and distributions of intramembrane particles on the fracture faces of the plasma membrane, which is most likely the mechanosensor. These findings stress the view that the high mechanosensitivity of the sensory hair results from its anatomy and not from a specialized perception mechanism. It is proposed that trap closure is triggered by a rise in the cytoplasmic concentration of Ca(2+) or a Ca(2+)-activated regulatory complex, which must exceed a threshold concentration. Since the Ca(2+) influx during a single action potential does not suffice to reach this threshold, at least two stimulations

  5. Changing response measures alters temporal summation in the receptor and spike potentials of the Limulus lateral eye.

    PubMed

    Kong, K L; Wasserman, G S

    1978-03-01

    Temporal summation and reciprocity were studied in the retinula and eccentric cells of the excised Limulus lateral eye as a function of variation in response measure: Using the latency instead of the peak of the receptor potential as a response measure produced considerably shorter critical durations. Using the area under the receptor potential as a response measure produced no critical duration up to a stimulus duration of 640 msec; instead, supersummation occurred at long durations. Similar effects were observed in the optic nerve spikes, where the response measures were first spike latency and maximum spike number sampled in time windows that ranged from 40 to 640 msec. The critical durations clearly depended on the response measure used and, when a 640-msec window was used, no critical duration occurred; supersummation again occurred. Increasing the sampling period within which maximum spike number was measured increased the critical duration and changed the formal properties from those characteristic of the receptor potential's peak to those characteristic of the receptor potential's area. The implications of the more central portions of the nervous system using different summation times for different perceptual tasks are discussed; it is suggested that the choice of response measures is crucial in studies of temporal summation.

  6. Spike timing-dependent long-term potentiation in ventral tegmental area dopamine cells requires PKC.

    PubMed

    Luu, Percy; Malenka, Robert C

    2008-07-01

    Long-term potentiation (LTP) of excitatory synapses on ventral tegmental area (VTA) dopamine (DA) cells is thought to play an important role in mediating some of the behavioral effects of drugs of abuse yet little is known about its underlying mechanisms. We find that spike timing-dependent LTP (STD LTP) in VTA DA cells is absent in slices prepared from mice previously administered cocaine, suggesting that cocaine-induced LTP and STD LTP share underlying mechanisms. This form of STD LTP is dependent on NMDA receptor (NMDAR) activation and a rise in postsynaptic calcium but surprisingly was not affected by an inhibitor of calcium/calmodulin-dependent protein kinase II (CaMKII). It was blocked by antagonists of conventional isoforms of PKC, whereas activation of protein kinase C (PKC) using a phorbol ester enhanced synaptic strength. These results suggest that NMDAR-mediated activation of PKC, but not CaMKII, is a critical trigger for LTP in VTA DA cells.

  7. 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

  8. Temperature dependence of action potential parameters in Aplysia neurons.

    PubMed

    Hyun, Nam Gyu; Hyun, Kwang-Ho; Lee, Kyungmin; Kaang, Bong-Kiun

    2012-01-01

    Although the effects of temperature changes on the activity of neurons have been studied in Aplysia, the reproducibility of the temperature dependence of the action potential (AP) parameters has not been verified. To this end, we performed experiments using Aplysia neurons. Fourteen AP parameters were analyzed using the long-term data series recorded during the experiments. Our analysis showed that nine of the AP parameters decreased as the temperature increased: the AP amplitude (A(AP)), membrane potential at the positive peak (V(pp)), interspike interval, first half (Δt(r1)) and last half (Δt(r2)) of the temperature rising phase, first half (Δt(f1)) and last half (Δt(f2)) of the temperature falling phase, AP (Δt(AP, 1/2)), and differentiated signal (Δt(DS, 1/2)) half-width durations. Five of the AP parameters increased with temperature: the differentiated signal amplitude (A(DS)), absolute value of the membrane potential at negative peak (|V(np)|), absolute value of the maximum slope of the AP during the temperature rising (|-MSR|) and falling (|MSF|) phases, and spiking frequency (Frequency). This work could provide the basis for a better understanding of the elementary processes underlying the temperature-dependent neuronal activity in Aplysia.

  9. Conscious awareness of action potentiates sensorimotor learning.

    PubMed

    Boutin, Arnaud; Blandin, Yannick; Massen, Cristina; Heuer, Herbert; Badets, Arnaud

    2014-10-01

    Many everyday skills are unconsciously learned through repetitions of the same behaviour by binding independent motor acts into unified sets of actions. However, our ability to be consciously aware of producing newly and highly trained motor skills raises the question of the role played by conscious awareness of action upon skill acquisition. In this study we strengthened conscious awareness of self-produced sequential finger movements by way of asking participants to judge their performance in terms of maximal fluency after each trial. Control conditions in which participants did not make any judgment or performance-unrelated judgments were also included. Findings indicate that conscious awareness of action, enhanced via subjective appraisal of motor efficiency, potentiates sensorimotor learning and skilful motor production in optimising the processing and sequencing of action units, as compared to the control groups. The current work lends support to the claim that the learning and skilful expression of sensorimotor behaviours might be grounded upon our ability to be consciously aware of our own motor capability and efficiency.

  10. Sparse and powerful cortical spikes.

    PubMed

    Wolfe, Jason; Houweling, Arthur R; Brecht, Michael

    2010-06-01

    Activity in cortical networks is heterogeneous, sparse and often precisely timed. The functional significance of sparseness and precise spike timing is debated, but our understanding of the developmental and synaptic mechanisms that shape neuronal discharge patterns has improved. Evidence for highly specialized, selective and abstract cortical response properties is accumulating. Singe-cell stimulation experiments demonstrate a high sensitivity of cortical networks to the action potentials of some, but not all, single neurons. It is unclear how this sensitivity of cortical networks to small perturbations comes about and whether it is a generic property of cortex. The unforeseen sensitivity to cortical spikes puts serious constraints on the nature of neural coding schemes.

  11. Action-potential broadening and endogenously sustained bursting are substrates of command ability in a feeding neuron of Pleurobranchaea.

    PubMed

    Gillette, R; Gillette, M U; Davis, W J

    1980-03-01

    1. The ventral white cells (VWC's) of the buccal ganglion of Pleurobranchaea, so named for their position and color, are a bilateral pair of neuron somata. Each sends a single axon out its contralateral stomatogastric nerve and has a dendritic field originating close to the soma. 2. The vwcs exhibit spontaneous episodes of prolonged depolarization (duration 1--4 min) accompanied by repetitive action-potential activity and separated by regular intervals of 3--30 min. Such prolonged burst episodes can be triggered by short pulses of depolarizing current. During the repetitive activity of the spontaneous bursts or that driven by imposed depolarization, the action potentials progressively broaden to 5--16 times their initial duration. 3. During spontaneous bursting or activity driven by imposed depolarization, the cyclic motor output of the feeding network is initiated or accelerated with a latency corresponding with the development of appreciable VWC spike broadening. When broadening of antidromic VWC spikes is suppressed by imposed hyperpolarization of the soma, the frequency of feeding cycles is significantly lower than when broadened spikes are allowed to develop. When trains of spikes are driven by depolarizing current, the motor output of the feeding network is not initiated until the VWC spikes have broadened to a repeatable "threshold" duration, regardless of the intensity of the depolarizing current. 4. The endogenous production of prolonged burst episodes, triggered by depolarizing current pulses, and progressive spike broadening can be demonstrated in the surgically isolated VWC soma. 5. The paired VWCs are strongly electrically coupled and display highly synchronous activity. They receive synaptic inputs from many previously identified interneurons of the feeding network and are thus reciprocally coupled within the network. 6. These results demonstrate that the capacity of this neuron to generate broadened action potentials during repetitive activity

  12. Phytoremediation potential of Brassica juncea in Cu-pyrene co-contaminated soil: comparing freshly spiked soil with aged soil.

    PubMed

    Chigbo, Chibuike; Batty, Lesley

    2013-11-15

    A comparison was made between the dissipation of pyrene as well as the uptake of copper (Cu) in soil freshly spiked with Cu, pyrene or Cu + pyrene and in aged soil. The potential of B juncea for phytoremediation was also investigated. The biomass of Brassica juncea significantly decreased (>50% reduction) in freshly spiked soil when compared to aged soil in all treatments. However, the accumulation of Cu in shoot was significantly reduced (60-88%) in aged soil after 60 days of planting. The total removal of Cu from co-contaminated soil was always higher (>2-3 fold) in aged soil than in freshly spiked soil when lower Cu concentration (50 mg kg(-1)) was co-contaminated with 250 or 500 mg kg(-1) of pyrene while in other co-contaminated treatments, the total removal of Cu from aged soil were significantly lower. The level of pyrene in both planted and un-planted freshly spiked soil decreased significantly (>67%) over the 60 days of plant trial. In aged soils, there were no significant differences in residual pyrene concentration between planted and unplanted soil. This suggests that the presence of B. juncea in aged soil did not enhance the dissipation of pyrene and that the prediction of pyrene dissipation in laboratory prepared soil may not have reflected the true situation in the fields.

  13. Vocal sequences suppress spiking in the bat auditory cortex while evoking concomitant steady-state local field potentials

    NASA Astrophysics Data System (ADS)

    Hechavarría, Julio C.; Beetz, M. Jerome; Macias, Silvio; Kössl, Manfred

    2016-12-01

    The mechanisms by which the mammalian brain copes with information from natural vocalization streams remain poorly understood. This article shows that in highly vocal animals, such as the bat species Carollia perspicillata, the spike activity of auditory cortex neurons does not track the temporal information flow enclosed in fast time-varying vocalization streams emitted by conspecifics. For example, leading syllables of so-called distress sequences (produced by bats subjected to duress) suppress cortical spiking to lagging syllables. Local fields potentials (LFPs) recorded simultaneously to cortical spiking evoked by distress sequences carry multiplexed information, with response suppression occurring in low frequency LFPs (i.e. 2–15 Hz) and steady-state LFPs occurring at frequencies that match the rate of energy fluctuations in the incoming sound streams (i.e. >50 Hz). Such steady-state LFPs could reflect underlying synaptic activity that does not necessarily lead to cortical spiking in response to natural fast time-varying vocal sequences.

  14. Vocal sequences suppress spiking in the bat auditory cortex while evoking concomitant steady-state local field potentials

    PubMed Central

    Hechavarría, Julio C.; Beetz, M. Jerome; Macias, Silvio; Kössl, Manfred

    2016-01-01

    The mechanisms by which the mammalian brain copes with information from natural vocalization streams remain poorly understood. This article shows that in highly vocal animals, such as the bat species Carollia perspicillata, the spike activity of auditory cortex neurons does not track the temporal information flow enclosed in fast time-varying vocalization streams emitted by conspecifics. For example, leading syllables of so-called distress sequences (produced by bats subjected to duress) suppress cortical spiking to lagging syllables. Local fields potentials (LFPs) recorded simultaneously to cortical spiking evoked by distress sequences carry multiplexed information, with response suppression occurring in low frequency LFPs (i.e. 2–15 Hz) and steady-state LFPs occurring at frequencies that match the rate of energy fluctuations in the incoming sound streams (i.e. >50 Hz). Such steady-state LFPs could reflect underlying synaptic activity that does not necessarily lead to cortical spiking in response to natural fast time-varying vocal sequences. PMID:27976691

  15. Ca2+ involvement in the action potential generation of myenteric neurones in the rat oesophagus.

    PubMed

    De Laet, A; Cornelissen, W; Adriaensen, D; Van Bogaert, P-P; Scheuermann, D W; Timmermans, J-P

    2002-04-01

    Intracellular recordings were used to study the physiological behaviour of rat oesophageal myenteric neurones, which are embedded in striated muscle. Injection of depolarizing pulses evoked action potentials with a clear 'shoulder' in all neurones. This shoulder disappeared under low Ca2+/high Mg2+ conditions. Tetrodotoxin (TTX; 1 micromol L-1) did not impede spike firing, whereas under combined TTX and low Ca2+/high Mg2+ conditions the action potentials were completely abolished, indicating that TTX- resistant action potentials are mediated by a Ca2+ current. Further experiments with omega-conotoxin GVIA (100 nmol L-1) revealed that these Ca2+ currents enter the cell via N-type voltage-activated Ca2+ channels (see also accompanying paper). Tetraethylammonium (10 mmol L-1) caused broadening of the action potentials, which probably resulted from prolonged Ca2+ influx due to blockade of the delayed rectifier K+ channel. Although Ca2+ appears to be involved in the spike generation of all rat oesophageal myenteric neurones, only a minority (14%) shows a slow afterhyperpolarization. Thus, no strict correlation exists between the presence of a shoulder and a slow afterhyperpolarization. Furthermore, morphological identification of 25 of the impaled neurones revealed that there was no strict correlation between morphology and electrophysiological behaviour. Consequently, rat oesophageal myenteric neurones appear to differ in several aspects from myenteric neurones in smooth muscle regions of the gastrointestinal tract.

  16. Motor control by precisely timed spike patterns.

    PubMed

    Srivastava, Kyle H; Holmes, Caroline M; Vellema, Michiel; Pack, Andrea R; Elemans, Coen P H; Nemenman, Ilya; Sober, Samuel J

    2017-01-31

    A fundamental problem in neuroscience is understanding how sequences of action potentials ("spikes") encode information about sensory signals and motor outputs. Although traditional theories assume that this information is conveyed by the total number of spikes fired within a specified time interval (spike rate), recent studies have shown that additional information is carried by the millisecond-scale timing patterns of action potentials (spike timing). However, it is unknown whether or how subtle differences in spike timing drive differences in perception or behavior, leaving it unclear whether the information in spike timing actually plays a role in brain function. By examining the activity of individual motor units (the muscle fibers innervated by a single motor neuron) and manipulating patterns of activation of these neurons, we provide both correlative and causal evidence that the nervous system uses millisecond-scale variations in the timing of spikes within multispike patterns to control a vertebrate behavior-namely, respiration in the Bengalese finch, a songbird. These findings suggest that a fundamental assumption of current theories of motor coding requires revision.

  17. Weber potential from finite velocity of action?

    NASA Astrophysics Data System (ADS)

    Wesley, J. P.

    1992-12-01

    The Weber potential energy U for charges q and q' separated by the distance R is U = (qq'/R)[1 - (dR/dt)2/2c2]. If this potential arises from a finite velocity c of energy transfer Q', where the retarded rate of transfer from q' to q is dQ(t-R/c)/dt = Q'[1 - (dR/dt)/c] and where the advanced rate from q to q' is dQ(t+R/c)/dt = Q'[1 + (dR/dt)/c], then the resultant time-average root-mean-square action is given by{{Q'}}sqrt {1 - {{({{{{{dR}}} {{{dt}}}}} )^2} {{{c}}^{{2}} }}} ≈ {{Q'}}[ {{{1 - }}{{( {{{{{dR}}} {{{dt}}}}} )^2 {{{{dR}}} {{{dt}}}}})^2 {2{{c}}^{{2}} }}}]. Identifying Q' with the Coulomb potential energy qq'/R, the Weber potential is obtained. Using the same argument, Newtonian gravitation yields a corresponding Weber potential energy, qq'/R being replaced by ( - Gmm'/R).

  18. Regulation of spike timing in visual cortical circuits

    PubMed Central

    Tiesinga, Paul; Fellous, Jean-Marc; Sejnowski, Terrence J.

    2010-01-01

    A train of action potentials (a spike train) can carry information in both the average firing rate and the pattern of spikes in the train. But can such a spike-pattern code be supported by cortical circuits? Neurons in vitro produce a spike pattern in response to the injection of a fluctuating current. However, cortical neurons in vivo are modulated by local oscillatory neuronal activity and by top-down inputs. In a cortical circuit, precise spike patterns thus reflect the interaction between internally generated activity and sensory information encoded by input spike trains. We review the evidence for precise and reliable spike timing in the cortex and discuss its computational role. PMID:18200026

  19. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.

    PubMed

    Raman, I M; Bean, B P

    1997-06-15

    Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive inward current was elicited when the membrane was repolarized to voltages between -60 and -20 mV after depolarizations to +30 mV long enough to produce maximal inactivation. At -40 mV, this "resurgent" current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on average approximately 120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at -40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at approximately 30 Hz. Hyperpolarization to -85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltage-clamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.

  20. Short-term response of sleep-potentiated spiking to high-dose diazepam in electric status epilepticus during sleep.

    PubMed

    Sánchez Fernández, Iván; Hadjiloizou, Stavros; Eksioglu, Yaman; Peters, Jurriaan M; Takeoka, Masanori; Tas, Emir; Abdelmoumen, Imane; Rotenberg, Alexander; Kothare, Sanjeev V; Riviello, James J; Loddenkemper, Tobias

    2012-05-01

    We describe the short-term effects of high-dose oral diazepam on sleep-potentiated epileptiform activity in patients with electric status epilepticus during sleep. We enrolled patients treated with high-dose oral bedtime diazepam from 2001-2009. We defined spike percentage as the percentage of 1-second bins containing at least one spike, and calculated it during three randomly selected 5-minute samples of wakefulness throughout the day and during the first 5 minutes of every hour of non-rapid eye movement sleep at night. In this study, patients were considered to demonstrate sleep-potentiated epileptiform activity when their spike percentage during sleep was increased by ≥50% compared with wakefulness. Twenty-nine children (18 boys) were included (median age, 7.4 years). Twenty-four hours after receiving high-dose diazepam, epileptiform activity was significantly reduced (76.7% at baseline vs 40.8% 24 hours after high-dose diazepam; Wilcoxon signed ranks test, Z = -4.287, P < 0.0001). Seven patients (24.1%) manifested mild, reversible side effects during the first 48 hours after diazepam administration. High-dose oral diazepam effectively and safely reduced epileptiform activity in patients with electric status epilepticus during sleep.

  1. Action-potential modulation during axonal conduction.

    PubMed

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2011-02-04

    Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.

  2. Mechanical Surface Waves Accompany Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    Machta, Benjamin; El Hady, Ahmed

    2015-03-01

    The action potential (AP) is the basic mechanism by which information is transmitted along neuronal axons. Although the excitable nature of axons is understood to be primarily electrical, many experimental studies have shown that a mechanical displacement of the axonal membrane co-propagates with the electrical signal. While the experimental evidence for co-propagating mechanical waves is diverse and compelling, there is no consensus for their physical underpinnings. We present a model in which these mechanical displacements arise from the driving of mechanical surface waves, in which potential energy is stored in elastic deformations of the neuronal membrane and cytoskeleton while kinetic energy is stored in the movement of the axoplasmic fluid. In our model these surface waves are driven by the traveling wave of electrical depolarization that characterizes the AP, altering the electrostatic forces across the membrane as it passes. Our model allows us to predict the shape of the displacement that should accompany any traveling wave of voltage, including the well-characterized AP. We expect our model to serve as a framework for understanding the physical origins and possible functional roles of these AWs in neurobiology. See Arxiv/1407.7600

  3. Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons

    PubMed Central

    Watanabe, Shigeo; Hoffman, Dax A.; Migliore, Michele; Johnston, Daniel

    2002-01-01

    We investigated the role of A-type K+ channels for the induction of long-term potentiation (LTP) of Schaffer collateral inputs to hippocampal CA1 pyramidal neurons. When low-amplitude excitatory postsynaptic potentials (EPSPs) were paired with two postsynaptic action potentials in a theta-burst pattern, N-methyl-d-aspartate (NMDA)-receptor-dependent LTP was induced. The amplitudes of the back-propagating action potentials were boosted in the dendrites only when they were coincident with the EPSPs. Mitogen-activated protein kinase (MAPK) inhibitors PD 098059 or U0126 shifted the activation of dendritic K+ channels to more hyperpolarized potentials, reduced the boosting of dendritic action potentials by EPSPs, and suppressed the induction of LTP. These results support the hypothesis that dendritic K+ channels and the boosting of back-propagating action potentials contribute to the induction of LTP in CA1 neurons. PMID:12048251

  4. Action Potential Initiation in Neocortical Inhibitory Interneurons

    PubMed Central

    Li, Tun; Tian, Cuiping; Scalmani, Paolo; Frassoni, Carolina; Mantegazza, Massimo; Wang, Yonghong; Yang, Mingpo; Wu, Si; Shu, Yousheng

    2014-01-01

    Action potential (AP) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV)- and somatostatin (SST)-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV) than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS) of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity. PMID:25203314

  5. Action potential processing in a detailed Purkinje cell model reveals a critical role for axonal compartmentalization

    PubMed Central

    Masoli, Stefano; Solinas, Sergio; D'Angelo, Egidio

    2015-01-01

    The Purkinje cell (PC) is among the most complex neurons in the brain and plays a critical role for cerebellar functioning. PCs operate as fast pacemakers modulated by synaptic inputs but can switch from simple spikes to complex bursts and, in some conditions, show bistability. In contrast to original works emphasizing dendritic Ca-dependent mechanisms, recent experiments have supported a primary role for axonal Na-dependent processing, which could effectively regulate spike generation and transmission to deep cerebellar nuclei (DCN). In order to account for the numerous ionic mechanisms involved (at present including Nav1.6, Cav2.1, Cav3.1, Cav3.2, Cav3.3, Kv1.1, Kv1.5, Kv3.3, Kv3.4, Kv4.3, KCa1.1, KCa2.2, KCa3.1, Kir2.x, HCN1), we have elaborated a multicompartmental model incorporating available knowledge on localization and gating of PC ionic channels. The axon, including initial segment (AIS) and Ranvier nodes (RNs), proved critical to obtain appropriate pacemaking and firing frequency modulation. Simple spikes initiated in the AIS and protracted discharges were stabilized in the soma through Na-dependent mechanisms, while somato-dendritic Ca channels contributed to sustain pacemaking and to generate complex bursting at high discharge regimes. Bistability occurred only following Na and Ca channel down-regulation. In addition, specific properties in RNs K currents were required to limit spike transmission frequency along the axon. The model showed how organized electroresponsive functions could emerge from the molecular complexity of PCs and showed that the axon is fundamental to complement ionic channel compartmentalization enabling action potential processing and transmission of specific spike patterns to DCN. PMID:25759640

  6. Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells.

    PubMed

    Storm, J F

    1987-03-20

    Intracellular recordings were made from CA1 pyramidal cells in rat hippocampal slices. Single action potentials were elicited by injection of brief current pulses. Bath application of phorbol esters (4 beta-phorbol-12,13-diacetate, 0.3-5 microM; or 4 beta-phorbol-12,13-dibutyrate, 5-10 microM) broadened the action potential in each of the cells tested (n = 9). The broadening reflected slowing of the repolarization, whereas the upstroke of the spike was unchanged. This effect may enhance transmitter release from synaptic terminals, and contribute to enhancement of synaptic transmission through activation of protein kinase C, a mechanism which has been associated with long term potentiation.

  7. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    PubMed

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H

    2007-06-21

    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  8. Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons

    PubMed Central

    Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

    2015-01-01

    Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt) preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding. PMID:26083350

  9. Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells.

    PubMed

    Storm, J F

    1987-04-01

    1. The repolarization of the action potential, and a fast after-hyperpolarization (a.h.p.) were studied in CA1 pyramidal cells (n = 76) in rat hippocampal slices (28-37 degrees C). Single spikes were elicited by brief (1-3 ms) current pulses, at membrane potentials close to rest (-60 to -70 mV). 2. Each action potential was followed by four after-potentials: (a) the fast a.h.p., lasting 2-5 ms; (b) an after-depolarization; (c) a medium a.h.p., (50-100 ms); and (d) a slow a.h.p. (1-2 s). Both the fast a.h.p. and the slow a.h.p. (but not the medium a.h.p.) were inhibited by Ca2+-free medium or Ca2+-channel blockers (Co2+, Mn2+ or Cd2+); but tetraethylammonium (TEA; 0.5-2 nM) blocked only the fast a.h.p., and noradrenaline (2-5 microM) only the slow a.h.p. This suggests that two Ca2+-activated K+ currents were involved: a fast, TEA-sensitive one (IC) underlying the fast a.h.p., and a slow noradrenaline-sensitive one (IAHP) underlying the slow a.h.p. 3. Like the fast a.h.p., spike repolarization seems to depend on a Ca2+-dependent K+ current of the fast, TEA-sensitive kind (IC). The repolarization was slowed by Ca2+-free medium, Co2+, Mn2+, Cd2+, or TEA, but not by noradrenaline. Charybdotoxin (CTX; 30 nM), a scorpion toxin which blocks the large-conductance Ca2+-activated K+ channel in muscle, had a similar effect to TEA. The effects of TEA and Cd2+ (or Mn2+) showed mutual occlusion. Raising the external K+ concentration reduced the fast a.h.p. and slowed the spike repolarization, whereas Cl- loading of the cell was ineffective. 4. The transient K+ current, IA, seems also to contribute to spike repolarization, because: (a) 4-aminopyridine (4-AP; 0.1 mM), which blocks IA, slowed the spike repolarization; (b) depolarizing pre-pulses, which inactivate IA, had a similar effect; (c) hyperpolarizing pre-pulses speeded up the spike repolarization; (d) the effects of 4-AP and pre-pulses persisted during Ca2+ blockade (like IA); and (e) depolarizing pre-pulses reduced the

  10. On the continuous differentiability of inter-spike intervals of synaptically connected cortical spiking neurons in a neuronal network.

    PubMed

    Kumar, Gautam; Kothare, Mayuresh V

    2013-12-01

    We derive conditions for continuous differentiability of inter-spike intervals (ISIs) of spiking neurons with respect to parameters (decision variables) of an external stimulating input current that drives a recurrent network of synaptically connected neurons. The dynamical behavior of individual neurons is represented by a class of discontinuous single-neuron models. We report here that ISIs of neurons in the network are continuously differentiable with respect to decision variables if (1) a continuously differentiable trajectory of the membrane potential exists between consecutive action potentials with respect to time and decision variables and (2) the partial derivative of the membrane potential of spiking neurons with respect to time is not equal to the partial derivative of their firing threshold with respect to time at the time of action potentials. Our theoretical results are supported by showing fulfillment of these conditions for a class of known bidimensional spiking neuron models.

  11. SHAPING OF ACTION POTENTIALS BY TYPE I AND TYPE II BK CHANNELS

    PubMed Central

    Jaffe, David B.; Wang, Bin; Brenner, Robert

    2011-01-01

    The BK channel is a Ca2+ and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca2+ was high (>20 µM) and the other where BK-activating Ca2+ was low (~0.4–1.2 µM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca2+ channels due to electrogenic effects on spike duration. We also found that depending on Ca2+ dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron. PMID:21723921

  12. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics.

    PubMed

    Kapucu, Fikret E; Tanskanen, Jarno M A; Mikkonen, Jarno E; Ylä-Outinen, Laura; Narkilahti, Susanna; Hyttinen, Jari A K

    2012-01-01

    In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESCs), exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI) histograms. Moreover, the algorithm calculates ISI thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average (CMA) and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA) data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  13. Action potential initiation and propagation in rat neocortical pyramidal neurons.

    PubMed

    Stuart, G; Schiller, J; Sakmann, B

    1997-12-15

    1. Initiation and propagation of action potentials evoked by extracellular synaptic stimulation was studied using simultaneous dual and triple patch pipette recordings from different locations on neocortical layer 5 pyramidal neurons in brain slices from 4-week-old rats (P26-30) at physiological temperatures. 2. Simultaneous cell-attached and whole-cell voltage recordings from the apical trunk (up to 700 microns distal to the soma) and the soma indicated that proximal synaptic stimulation (layer 4) initiated action potentials first at the soma, whereas distal stimulation (upper layer 2/3) could initiate dendritic regenerative potentials prior to somatic action potentials following stimulation at higher intensity. 3. Somatic action potentials, once initiated, propagated back into the apical dendrites in a decremented manner which was frequency dependent. The half-width of back propagating action potentials increased and their maximum rate of rise decreased with distance from the soma, with the peak of these action potentials propagating with a conduction velocity of approximately 0.5 m s-1. 4. Back-propagation of action potentials into the dendritic tree was associated with dendritic calcium electrogenesis, which was particularly prominent during bursts of somatic action potentials. 5. When dendritic regenerative potentials were evoked prior to somatic action potentials, the more distal the dendritic recording was made from the soma the longer the time between the onset of the dendritic regenerative potential relative to somatic action potential. This suggested that dendritic regenerative potentials were initiated in the distal apical dendrites, possibly in the apical tuft. 6. At any one stimulus intensity, the initiation of dendritic regenerative potentials prior to somatic action potentials could fluctuate, and was modulated by depolarizing somatic or hyperpolarizing dendritic current injection. 7. Dendritic regenerative potentials could be initiated prior to

  14. Robustness of retrieval properties against imbalance between long-term potentiation and depression of spike-timing-dependent plasticity

    NASA Astrophysics Data System (ADS)

    Matsumoto, Narihisa; Okada, Masato

    2003-12-01

    Spike-timing-dependent plasticity (STDP) has recently been shown in some physiological studies. STDP depends on the precise temporal relationship of presynaptic and postsynaptic spikes. Many authors have indicated that a precise balance between long-term potentiation (LTP) and long-term depression (LTD) of STDP is significant for a stable learning. However, a situation in which the balance is maintained precisely is inconceivable in the brain. Using a method of the statistical neurodynamics, we show robust retrieval properties of spatiotemporal patterns in an associative memory model against the imbalance between LTP and LTD. When the fluctuation of LTD is assumed to obey a Gaussian distribution with mean 0 and variance δ2, the storage capacity takes a finite value even at large δ. This means that the balance between LTP and LTD of STDP need not be maintained precisely, but must be maintained on average. Furthermore, we found that the basin of attraction becomes smaller as δ increases while an initial critical overlap remains unchanged.

  15. Modulation of presynaptic action potential kinetics underlies synaptic facilitation of type B photoreceptors after associative conditioning in Hermissenda.

    PubMed

    Gandhi, C C; Matzel, L D

    2000-03-01

    Descriptions of conditioned response generation in Hermissenda stipulate that the synaptic interaction between type B and A photoreceptors should be enhanced after associative pairings of light and rotation. Although evidence from several laboratories has confirmed this assumption, the mechanism underlying this synaptic facilitation has not been elucidated. Here we report that in vitro conditioning (i.e., light paired with stimulation of vestibular hair cells) modifies the kinetics of presynaptic action potentials in the B photoreceptor in a manner sufficient to account for this synaptic facilitation. After paired training, we observed an increase in the duration of evoked action potentials and a decrease in the amplitude of the spike afterhyperpolarization in the B-cell. As previously reported, paired training also enhanced the excitability (i.e., input resistance and evoked spike rate) of the B photoreceptor. In a second experiment, simultaneous recordings were made in type B and A photoreceptors, and paired training was found to produce an increase in the amplitude of the IPSP in the A photoreceptor in response to an evoked spike in the B-cell. Importantly, there was no change in the initial slope of the postsynaptic IPSP in the A photoreceptor, suggesting that spike duration-independent mechanisms of neurotransmitter exocytosis or postsynaptic receptor sensitivity did not contribute to the observed synaptic facilitation. Perfusion of 4-aminopyridine (4-AP) mimicked a known effect of behavioral conditioning in that it specifically reduced the amplitude of the transient voltage-dependent K(+) current (I(A)) in the B-cell, but in addition, produced action potential broadening and synaptic facilitation that was analogous to that observed after in vitro conditioning. Finally, the effect of 4-AP on B-cell action potentials and on the postsynaptic IPSP in the A-cell was occluded by previous paired (but not unpaired) training, suggesting that the prolongation of the B

  16. Conduction velocity of antigravity muscle action potentials.

    PubMed

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.

  17. Frequency-dependent action potential prolongation in Aplysia pleural sensory neurones.

    PubMed

    Edstrom, J P; Lukowiak, K D

    1985-10-01

    The effects of repetitive activity on action-potential shape in Aplysia californica pleural sensory cells are described. Action potentials were evoked by intracellular current injection at frequencies between 7.41 and 0.2 Hz. In contrast to other molluscan neurons having brief action potentials, it was found that at these firing rates the normally brief action potential develops a prominent shoulder or plateau during the repolarization phase. Higher stimulus rates broaden the action potential more rapidly and to a greater extent than lower stimulus rates. Inactivation is slow relative to activation; effects of 3-s 6-Hz trains are detectable after 1 min rest. The amplitude of the plateau voltage reaches a maximum of 50-70 mV at the highest stimulus rates tested. Frequency-dependent increases in action-potential duration measured at half-amplitude normally range between 6 and 15 ms. Cadmium, at concentrations between 0.05 and 0.5 mM, antagonizes frequency-dependent broadening. The increases in duration induced by repetitive activity are more sensitive to cadmium than are the increases in plateau amplitude. Tetraethylammonium, at concentrations between 0.5 and 10 mM, slightly increases the duration and amplitude of single action potentials. During repetitive activity at high stimulus rates the maximum duration and rate of broadening are both increased but the amplitude of the plateau potential is not affected by these tetraethylammonium concentrations. Above 10 mM, tetraethylammonium greatly increases the duration and amplitude of single action potentials as well as the rates of action-potential duration and amplitude increase during repetitive activity. These high tetraethylammonium concentrations also cause the normally smoothly increasing duration and amplitude to reach a maximum value early in a train and then decline slowly during the remainder of the train. The consequences of frequency-dependent spike broadening in these neurons have not yet been investigated

  18. The Global Spike: Conserved Dendritic Properties Enable Unique Ca2+ Spike Generation in Low-Threshold Spiking Neurons

    PubMed Central

    Connelly, William M.; Crunelli, Vincenzo

    2015-01-01

    Low-threshold Ca2+ spikes (LTS) are an indispensible signaling mechanism for neurons in areas including the cortex, cerebellum, basal ganglia, and thalamus. They have critical physiological roles and have been strongly associated with disorders including epilepsy, Parkinson's disease, and schizophrenia. However, although dendritic T-type Ca2+ channels have been implicated in LTS generation, because the properties of low-threshold spiking neuron dendrites are unknown, the precise mechanism has remained elusive. Here, combining data from fluorescence-targeted dendritic recordings and Ca2+ imaging from low-threshold spiking cells in rat brain slices with computational modeling, the cellular mechanism responsible for LTS generation is established. Our data demonstrate that key somatodendritic electrical conduction properties are highly conserved between glutamatergic thalamocortical neurons and GABAergic thalamic reticular nucleus neurons and that these properties are critical for LTS generation. In particular, the efficiency of soma to dendrite voltage transfer is highly asymmetric in low-threshold spiking cells, and in the somatofugal direction, these neurons are particularly electrotonically compact. Our data demonstrate that LTS have remarkably similar amplitudes and occur synchronously throughout the dendritic tree. In fact, these Ca2+ spikes cannot occur locally in any part of the cell, and hence we reveal that LTS are generated by a unique whole-cell mechanism that means they always occur as spatially global spikes. This all-or-none, global electrical and biochemical signaling mechanism clearly distinguishes LTS from other signals, including backpropagating action potentials and dendritic Ca2+/NMDA spikes, and has important consequences for dendritic function in low-threshold spiking neurons. SIGNIFICANCE STATEMENT Low-threshold Ca2+ spikes (LTS) are critical for important physiological processes, including generation of sleep-related oscillations, and are

  19. Centrotemporal spikes during NREM sleep: The promoting action of thalamus revealed by simultaneous EEG and fMRI coregistration.

    PubMed

    Mirandola, Laura; Cantalupo, Gaetano; Vaudano, Anna Elisabetta; Avanzini, Pietro; Ruggieri, Andrea; Pisani, Francesco; Cossu, Giuseppe; Tassinari, Carlo Alberto; Nichelli, Paolo Frigio; Benuzzi, Francesca; Meletti, Stefano

    2013-01-01

    Benign childhood epilepsy with centrotemporal spikes (BECTS) has been investigated through EEG-fMRI with the aim of localizing the generators of the epileptic activity, revealing, in most cases, the activation of the sensory-motor cortex ipsilateral to the centrotemporal spikes (CTS). In this case report, we investigated the brain circuits hemodynamically involved by CTS recorded during wakefulness and sleep in one boy with CTS and a language disorder but without epilepsy. For this purpose, the patient underwent EEG-fMRI coregistration. During the "awake session", fMRI analysis of right-sided CTS showed increments of BOLD signal in the bilateral sensory-motor cortex. During the "sleep session", BOLD increments related to right-sided CTS were observed in a widespread bilateral cortical-subcortical network involving the thalamus, basal ganglia, sensory-motor cortex, perisylvian cortex, and cerebellum. In this patient, who fulfilled neither the diagnostic criteria for BECTS nor that for electrical status epilepticus in sleep (ESES), the transition from wakefulness to sleep was related to the involvement of a widespread cortical-subcortical network related to CTS. In particular, the involvement of a thalamic-perisylvian neural network similar to the one previously observed in patients with ESES suggests a common sleep-related network dysfunction even in cases with milder phenotypes without seizures. This finding, if confirmed in a larger cohort of patients, could have relevant therapeutic implication.

  20. Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials

    NASA Astrophysics Data System (ADS)

    Lopour, Beth A.; Staba, Richard J.; Stern, John M.; Fried, Itzhak; Ringach, Dario L.

    2016-04-01

    Objective. Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach. Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results. We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance. The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity

  1. Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long-term potentiation in vivo.

    PubMed

    Fernández-Ruiz, Antonio; Makarov, Valeri A; Herreras, Oscar

    2012-01-01

    Long-term potentiation (LTP) is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes it difficult to estimate the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs) in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency) that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average (STA) of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway-specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. They indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

  2. Differential effects of pentylenetetrazol-kindling on long-term potentiation of population excitatory postsynaptic potentials and population spikes in the CA1 region of rat hippocampus.

    PubMed

    Palizvan, M R; Fathollahi, Y; Semnanian, S; Hajezadeh, S; Mirnajafizadh, J

    2001-04-13

    The effects of pentylenetetrazol-kindling on synaptic transmission and the effectiveness of θ pattern primed-bursts (PBs) for the induction of long-term potentiation (LTP) of population excitatory postsynaptic potentials and population spikes were investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the control and kindled animals at two post-kindling periods, i.e., 48-144 h (early phase) and 30-33 days (long lasting phase). Field potentials (population excitatory postsynaptic potentials, pEPSPs; and population spikes, PSs) were recorded at the stratum radiatum and the stratum pyramidale following stimulation of the stratum fibers, respectively. PBs were delivered to stratum fibers and PB potentiation was assessed. The results showed that 48-144 h after kindling there was no significant difference for pEPSP slope and PS amplitude between two groups. But at 30-33 days after kindling, the pEPSP slope in the stratum radiatum of kindled animals decreased, whereas the amplitude of PSs increased compared to those of controls. Shortly after kindling, control animals had normal LTP of pEPSP slope and PS amplitude in response to PBs, but kindled rats lack LTP of pEPSP slope and PBs induced LTP of PS amplitude in most of kindled animals. In 30-33 days after kindling, PB potentiation was not observed in the stratum radiatum of kindled animals but PBs induced LTP of PS amplitude, which was significantly greater than that of control animals. The effect is compatible with the hypothesis, which postulates kindling-associated functional deficit in hippocampus, especially CA1, as an explanation for the behavioral deficits seen with the kindling model of epilepsy.

  3. Controlling chaos in balanced neural circuits with input spike trains

    NASA Astrophysics Data System (ADS)

    Engelken, Rainer; Wolf, Fred

    The cerebral cortex can be seen as a system of neural circuits driving each other with spike trains. Here we study how the statistics of these spike trains affects chaos in balanced target circuits.Earlier studies of chaos in balanced neural circuits either used a fixed input [van Vreeswijk, Sompolinsky 1996, Monteforte, Wolf 2010] or white noise [Lajoie et al. 2014]. We study dynamical stability of balanced networks driven by input spike trains with variable statistics. The analytically obtained Jacobian enables us to calculate the complete Lyapunov spectrum. We solved the dynamics in event-based simulations and calculated Lyapunov spectra, entropy production rate and attractor dimension. We vary correlations, irregularity, coupling strength and spike rate of the input and action potential onset rapidness of recurrent neurons.We generally find a suppression of chaos by input spike trains. This is strengthened by bursty and correlated input spike trains and increased action potential onset rapidness. We find a link between response reliability and the Lyapunov spectrum. Our study extends findings in chaotic rate models [Molgedey et al. 1992] to spiking neuron models and opens a novel avenue to study the role of projections in shaping the dynamics of large neural circuits.

  4. Biophysical mechanism of spike threshold dependence on the rate of rise of the membrane potential by sodium channel inactivation or subthreshold axonal potassium current.

    PubMed

    Wester, Jason C; Contreras, Diego

    2013-08-01

    Spike threshold filters incoming inputs and thus gates activity flow through neuronal networks. Threshold is variable, and in many types of neurons there is a relationship between the threshold voltage and the rate of rise of the membrane potential (dVm/dt) leading to the spike. In primary sensory cortex this relationship enhances the sensitivity of neurons to a particular stimulus feature. While Na⁺ channel inactivation may contribute to this relationship, recent evidence indicates that K⁺ currents located in the spike initiation zone are crucial. Here we used a simple Hodgkin-Huxley biophysical model to systematically investigate the role of K⁺ and Na⁺ current parameters (activation voltages and kinetics) in regulating spike threshold as a function of dVm/dt. Threshold was determined empirically and not estimated from the shape of the Vm prior to a spike. This allowed us to investigate intrinsic currents and values of gating variables at the precise voltage threshold. We found that Na⁺ nactivation is sufficient to produce the relationship provided it occurs at hyperpolarized voltages combined with slow kinetics. Alternatively, hyperpolarization of the K⁺ current activation voltage, even in the absence of Na⁺ inactivation, is also sufficient to produce the relationship. This hyperpolarized shift of K⁺ activation allows an outward current prior to spike initiation to antagonize the Na⁺ inward current such that it becomes self-sustaining at a more depolarized voltage. Our simulations demonstrate parameter constraints on Na⁺ inactivation and the biophysical mechanism by which an outward current regulates spike threshold as a function of dVm/dt.

  5. Theophylline-induced potentiation of the antinociceptive action of baclofen.

    PubMed

    Sawynok, J

    1983-02-01

    1--Theophylline (35, 50 mg/kg) potentiated the antinociceptive action of intraperitoneally administered baclofen in the tail flick and hot plate tests. Potentiation was most marked when the pretreatment time was 1 h, but some potentiation was still apparent following a 2 h pretreatment. 2--Theophylline alone (50 mg/kg) produced only slight alterations in reaction latency in the two tests. 3--When baclofen was applied directly into the spinal subarachnoid space, a 1 h pretreatment with theophylline produced minimal effects, but a 2 h pretreatment produced an increase in the antinociceptive action of baclofen. 4--These results suggest that theophylline can potentiate the antinociceptive action of baclofen by actions at both supraspinal and spinal sites.

  6. Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

    PubMed

    Targ, E F; Kocsis, J D

    1986-01-15

    The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

  7. Dendritic NMDA spikes are necessary for timing-dependent associative LTP in CA3 pyramidal cells

    PubMed Central

    Brandalise, Federico; Carta, Stefano; Helmchen, Fritjof; Lisman, John; Gerber, Urs

    2016-01-01

    The computational repertoire of neurons is enhanced by regenerative electrical signals initiated in dendrites. These events, referred to as dendritic spikes, can act as cell-intrinsic amplifiers of synaptic input. Among these signals, dendritic NMDA spikes are of interest in light of their correlation with synaptic LTP induction. Because it is not possible to block NMDA spikes pharmacologically while maintaining NMDA receptors available to initiate synaptic plasticity, it remains unclear whether NMDA spikes alone can trigger LTP. Here we use dendritic recordings and calcium imaging to analyse the role of NMDA spikes in associative LTP in CA3 pyramidal cells. We show that NMDA spikes produce regenerative branch-specific calcium transients. Decreasing the probability of NMDA spikes reduces LTP, whereas increasing their probability enhances LTP. NMDA spikes and LTP occur without back-propagating action potentials. However, action potentials can facilitate LTP induction by promoting NMDA spikes. Thus, NMDA spikes are necessary and sufficient to produce the critical postsynaptic depolarization required for associative LTP in CA3 pyramidal cells. PMID:27848967

  8. Properties and ionic basis of the action potentials in the periaqueductal grey neurones of the guinea-pig.

    PubMed Central

    Sánchez, D; Ribas, J

    1991-01-01

    1. Action potentials of neurones of the ventral part of the guinea-pig periaqueductal grey (PAG) were studied by intracellular recording in a mesencephalic slice preparation maintained in vitro. 2. Fast spikes spontaneously fired last 2.8 +/- 0.6 ms (mean +/- S.D.) and have an amplitude of 72.3 +/- 5.3 mV (n = 28). The neurones could be antidromically activated from the neighbouring white matter and these spikes show an initial segment component that triggers the soma-dendritic spike. These two components were dissociated by hyperpolarization. Action potentials are Na+ dependent and a Ca2+ conductance is responsible for the hump on the falling phase. Hyperpolarization makes the hump disappear and a faster rate of rise and fall are seen. Accommodation of the firing threshold is observed in response to depolarizing ramps, which is eliminated with hyperpolarization. 3. High-threshold Ca2+ spikes are evoked in either Na(+)-free solution or in the presence of tetrodotoxin (TTX). These presumed dendritic action potentials display a fast repolarization and a large after-hyperpolarization (AHP) that prevent repetitive firing. This AHP is mainly generated by Ca(2+)-dependent K+ conductances. 4. The repolarization of fast action potentials depends on the activation of K+ conductances as well as a Na+ inactivation process. A fast-activated tetraethyl-ammonium (TEA)-sensitive K+ conductance, that could be Ca2+ dependent, and a K+ conductance blocked by apamin seem to be involved in the repolarization. 5. Each fast action potential is followed by a pronounced AHP with two components, an initial fast and a slow decaying phase. Membrane hyperpolarization around -60 mV eliminated the first component and the AHP acquired a plateau-like shape. At -90 mV the AHP was nullified. The slow phase was Ca2+ dependent and an apamin-sensitive K+ conductance is involved in its generation. This conductance may be active during the early part of the AHP, but a fast-activated TEA-sensitive K

  9. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FAILS TO ALTER FLASH OR PATTERN REVERSAL EVOKED POTENTIALS IN RATS.

    EPA Science Inventory

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Visual disturbances are often reported following exposure to xenobiotics, and cholinesterase-inhibiting compounds have been reported to alter visual functi...

  10. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons.

    PubMed

    Colbert, C M; Johnston, D

    1996-11-01

    A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

  11. Total synthesis of isotopically enriched Si-29 silica NPs as potential spikes for isotope dilution quantification of natural silica NPs.

    PubMed

    Pálmai, Marcell; Szalay, Roland; Bartczak, Dorota; Varga, Zoltán; Nagy, Lívia Naszályi; Gollwitzer, Christian; Krumrey, Michael; Goenaga-Infante, Heidi

    2015-05-01

    A new method was developed for the preparation of highly monodisperse isotopically enriched Si-29 silica nanoparticles ((29)Si-silica NPs) with the purpose of using them as spikes for isotope dilution mass spectrometry (IDMS) quantification of silica NPs with natural isotopic distribution. Si-29 tetraethyl orthosilicate ((29)Si-TEOS), the silica precursor was prepared in two steps starting from elementary silicon-29 pellets. In the first step Si-29 silicon tetrachloride ((29)SiCl4) was prepared by heating elementary silicon-29 in chlorine gas stream. By using a multistep cooling system and the dilution of the volatile and moisture-sensitive (29)SiCl4 in carbon tetrachloride as inert medium we managed to reduce product loss caused by evaporation. (29)Si-TEOS was obtained by treating (29)SiCl4 with absolute ethanol. Structural characterisation of (29)Si-TEOS was performed by using (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy and Fourier-transform infrared (FTIR) spectroscopy. For the NP preparation, a basic amino acid catalysis route was used and the resulting NPs were analysed using transmission electron microscopy (TEM), small angle X-ray scattering (SAXS), dynamic light scattering (DLS) and zeta potential measurements. Finally, the feasibility of using enriched NPs for on-line field-flow fractionation coupled with multi-angle light scattering and inductively coupled plasma mass spectrometry (FFF/MALS/ICP-MS) has been demonstrated.

  12. Dopamine gates action potential backpropagation in midbrain dopaminergic neurons.

    PubMed

    Gentet, Luc J; Williams, Stephen R

    2007-02-21

    Dopamine is released from both axonal and somatodendritic sites of midbrain dopaminergic neurons in an action potential-dependent manner. In contrast to the majority of central neurons, the axon of dopaminergic neurons typically originates from a dendritic site, suggesting a specialized computational function. Here, we examine the initiation and spread of action potentials in dopaminergic neurons of the substantia nigra pars reticulata and reveal that the displacement of the axon to a dendritic site allows highly compartmentalized electrical signaling. In response to a train of synaptic input, action potentials initiated at axon-bearing dendritic sites formed a variable trigger for invasion to the soma and contralateral dendritic tree, with action potentials often confined to the axon-bearing dendrite. The application of dopamine increased this form of electrical compartmentalization, an effect mediated by a tonic membrane potential hyperpolarization leading to an increased availability of a class of voltage-dependent potassium channel. These data suggest that the release of dopamine from axonal and somatodendritic sites are dissociable, and that dopamine levels within the midbrain are dynamically controlled by the somatodendritic spread of action potentials.

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

    PubMed Central

    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. PMID:26539072

  14. Substance P modulates sensory action potentials in the lamprey via a protein kinase C-mediated reduction of a 4-aminopyridine-sensitive potassium conductance.

    PubMed

    Parker, D; Svensson, E; Grillner, S

    1997-10-01

    We have examined the effects of the tachykinin substance P on the action potential of lamprey mechanosensory dorsal cells. Substance P increased the spike duration and reduced the afterhyperpolarization. These effects were mimicked by stimulation of the dorsal root, which contains tachykinin-like immunoreactive fibres. The tachykinin antagonist spantide II blocked the effects of both substance P and dorsal root stimulation. The spike broadening was voltage-dependent, and was due to the reduction of a 4-aminopyridine-sensitive potassium conductance. The spike broadening was mimicked by G-protein activators and blocked by the G-protein inhibitor GDPbetaS. Pertussis toxin did not block the effects of substance P. The spike broadening was blocked by the protein kinase C and cAMP-dependent protein kinase inhibitor H7, and by the specific protein kinase C antagonist chelerythrine, but not by the cAMP and cGMP-dependent protein kinase inhibitor H8. The phorbol ester phorbol 12,13-dibutyrate mimicked and blocked the effects of substance P, supporting the role of protein kinase C in the spike modulation. The adenylate cyclase activator forskolin and the cAMP agonist SpcAMPs mimicked but did not block the effects of substance P on the spike duration, suggesting that protein kinase A also modulates the dorsal cell action potential, but that substance P acts independently of this pathway. Substance P also increased the excitability of the dorsal cells. This effect was blocked by 4-AP, PDBu and chelerythrine, but not by H8, suggesting that the increase in excitability shares the same intracellular and effector pathways as the spike broadening.

  15. Sodium-activated potassium conductance participates in the depolarizing afterpotential following a single action potential in rat hippocampal CA1 pyramidal cells.

    PubMed

    Liu, Xinhuai; Stan Leung, L

    2004-10-15

    The depolarizing afterpotential (DAP) following an action potential increases the excitability of a neuron. Mechanisms related to the DAP following an antidromic or current-induced spike were studied in CA1 pyramidal cells by whole-cell recordings in hippocampal slices in vitro. In DAP-holding voltage curves, the DAP at 10 ms after the spike peak (DAP10) was extrapolated to reverse at about -50 mV. Increase of extracellular K(+) concentration increased DAP and neuronal bursting. DAP10 reversal potential shifted positively with an increase in [K(+)](o) and with the blockade of K(+) conductance using pipettes filled with Cs(+). Similarly, extracellular tetraethylammonium (TEA; 10 mM), 4-aminopyridine (3-10 mM) increased DAP and shifted the DAP10 reversal potential to a depolarizing direction. Decrease of [Ca(2+)](o) did not alter DAP significantly, suggesting a nonessential role of Ca(2+) in the DAP. Perfusion of tetrodotoxin (TTX; 0.1-1 microM) and replacement of extracellular Na(+) by choline(+) suppressed both spike height and DAP simultaneously. Replacement of extracellular Na(+) by Li(+) increased DAP and spike bursts, and caused a positive shift of the DAP10 reversal potential. It is suggested that Li(+) increased DAP by blocking an Na(+)-activated K(+) current. In summary, multiple K(+) conductances are normally active during the DAP following a single action potential.

  16. Frequency decoding of periodically timed action potentials through distinct activity patterns in a random neural network

    NASA Astrophysics Data System (ADS)

    Reichenbach, Tobias; Hudspeth, A. J.

    2012-11-01

    Frequency discrimination is a fundamental task of the auditory system. The mammalian inner ear, or cochlea, provides a place code in which different frequencies are detected at different spatial locations. However, a temporal code based on spike timing is also available: action potentials evoked in an auditory-nerve fiber by a low-frequency tone occur at a preferred phase of the stimulus—they exhibit phase locking—and thus provide temporal information about the tone's frequency. Humans employ this temporal information for discrimination of low frequencies. How might such temporal information be read out in the brain? Here we employ statistical and numerical methods to demonstrate that recurrent random neural networks in which connections between neurons introduce characteristic time delays, and in which neurons require temporally coinciding inputs for spike initiation, can perform sharp frequency discrimination when stimulated with phase-locked inputs. Although the frequency resolution achieved by such networks is limited by the noise in phase locking, the resolution for realistic values reaches the tiny frequency difference of 0.2% that has been measured in humans.

  17. Status epilepticus enhances tonic GABA currents and depolarizes GABA reversal potential in dentate fast-spiking basket cells

    PubMed Central

    Yu, Jiandong; Proddutur, Archana; Elgammal, Fatima S.; Ito, Takahiro

    2013-01-01

    Temporal lobe epilepsy is associated with loss of interneurons and inhibitory dysfunction in the dentate gyrus. While status epilepticus (SE) leads to changes in granule cell inhibition, whether dentate basket cells critical for regulating granule cell feedforward and feedback inhibition express tonic GABA currents (IGABA) and undergo changes in inhibition after SE is not known. We find that interneurons immunoreactive for parvalbumin in the hilar-subgranular region express GABAA receptor (GABAAR) δ-subunits, which are known to underlie tonic IGABA. Dentate fast-spiking basket cells (FS-BCs) demonstrate baseline tonic IGABA blocked by GABAAR antagonists. In morphologically and physiologically identified FS-BCs, tonic IGABA is enhanced 1 wk after pilocarpine-induced SE, despite simultaneous reduction in spontaneous inhibitory postsynaptic current (sIPSC) frequency. Amplitude of tonic IGABA in control and post-SE FS-BCs is enhanced by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), demonstrating the contribution of GABAAR δ-subunits. Whereas FS-BC resting membrane potential is unchanged after SE, perforated-patch recordings from FS-BCs show that the reversal potential for GABA currents (EGABA) is depolarized after SE. In model FS-BCs, increasing tonic GABA conductance decreased excitability when EGABA was shunting and increased excitability when EGABA was depolarizing. Although simulated focal afferent activation evoked seizurelike activity in model dentate networks with FS-BC tonic GABA conductance and shunting EGABA, excitability of identical networks with depolarizing FS-BC EGABA showed lower activity levels. Thus, together, post-SE changes in tonic IGABA and EGABA maintain homeostasis of FS-BC activity and limit increases in dentate excitability. These findings have implications for normal FS-BC function and can inform studies examining comorbidities and therapeutics following SE. PMID:23324316

  18. A fast algorithm for estimating actions in triaxial potentials

    NASA Astrophysics Data System (ADS)

    Sanders, Jason L.; Binney, James

    2015-03-01

    We present an approach to approximating rapidly the actions in a general triaxial potential. The method is an extension of the axisymmetric approach presented by Binney, and operates by assuming that the true potential is locally sufficiently close to some Stäckel potential. The choice of Stäckel potential and associated ellipsoidal coordinates is tailored to each individual input phase-space point. We investigate the accuracy of the method when computing actions in a triaxial Navarro-Frenk-White potential. The speed of the algorithm comes at the expense of large errors in the actions, particularly for the box orbits. However, we show that the method can be used to recover the observables of triaxial systems from given distribution functions to sufficient accuracy for the Jeans equations to be satisfied. Consequently, such models could be used to build models of external galaxies as well as triaxial components of our own Galaxy. When more accurate actions are required, this procedure can be combined with torus mapping to produce a fast convergent scheme for action estimation.

  19. Membrane, action, and oscillatory potentials in simulated protocells

    NASA Technical Reports Server (NTRS)

    Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

    1982-01-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

  20. Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium.

    PubMed

    Bárándi, László; Harmati, Gábor; Horváth, Balázs; Szentandrássy, Norbert; Magyar, János; Varró, András; Nánási, Péter P; Bányász, Tamás

    2010-09-01

    Several cardioactive agents exhibit direct or reverse rate-dependent effects on action potential duration (APD) depending on the experimental conditions. Recently, a new theory has been proposed, suggesting that the reverse rate-dependent mode of drug-action may be a common property of canine, rabbit, guinea pig and human cardiac tissues, and this phenomenon is based on the dependence of drug-action on baseline APD. The aim of the present work was to examine the limitations of this hypothesis by studying the APD lengthening effect of K(+) channel blockers and the APD shortening effect of Ca(2+) channel blockers during the electrical restitution process of rat ventricular action potentials. Rat ventricular muscle was chosen because it has a set of ion currents markedly different from those of other species, its APD is shorter by one order of magnitude than that of the "plateau-forming" larger mammals, and most importantly, its APD increases at higher heart rates - opposite to many other species. The restitution of APD was studied as a function of the diastolic interval, a parameter indicating the proximity of action potentials. It was found that drug-induced APD changes in rat myocardium are proportional with the pre-drug value of APD but not with the diastolic interval, indicating that not the proximity of consecutive action potentials, but the baseline APD itself may determine the magnitude of drug-induced APD changes.

  1. Layer I neurons of rat neocortex. I. Action potential and repetitive firing properties.

    PubMed

    Zhou, F M; Hablitz, J J

    1996-08-01

    1. Whole cell patch-clamp techniques, combined with direct visualization of neurons, were used to study action potential (AP) and repetitive firing properties of layer I neurons in slices of rat neocortex. 2. Layer I neurons had resting membrane potentials (RMP) of -59.8 +/- 4.7 mV (mean +/- SD) and input resistances (RN) of 592 +/- 284 M Omega. Layer II/III pyramidal neurons had RMPs and RNs of -61.5 +/- 5.6 mV and 320 +/- 113 M omega, respectively. A double exponential function was needed to describe the charging curves of both neuron types. In layer I neurons, tau(0) was 45 +/- 22 ms and tau(1) was 5 +/- 3.3 ms whereas in layer II/III pyramidal neurons, tau(0) was 41 +/- 11 ms and tau(1) was 3 +/- 2.6 ms. Estimates of specific membrane resistance (Rm) for layer I and layer II/III cells were 45 +/- 22 and 41 +/- 11 k omega cm2, respectively (Cm was assumed to be 1 microF/cm2). 3. AP threshold was -41 +/- 2 mV in layer I neurons. Spike amplitudes, measured from threshold to peak, were 90.6 +/- 7.7 mV. AP durations, measured both at the base and half maximal amplitude, were 2.5 +/- 0.4 and 1.1 +/- 0.2 ms, respectively. AP 10-90% rise and repolarization times were 0.6 +/- 0.1 and 1.1 +/- 0.2 ms, respectively. In layer II/III pyramidal neurons, AP threshold was -41 +/- 2.5 mV and spike amplitude was 97 +/- 9.7 mV. AP duration at base and half maximal amplitude was 5.4 +/- 1.1 ms and 1.8 +/- 0.2 ms, respectively. AP 10-90% rise and decay times were 0.6 +/- 0.1 ms and 2.8 +/- 0.6 ms, respectively. 4. Layer I neurons were fast spiking cells that showed little frequency adaptation, a large fast afterhyperpolarization (fAHP), and no slow afterhyperpolarization (sAHP). Some cells had a medium afterhyperpolarization (mAHP) and a slow afterdepolarization (sADP). All pyramidal cells in layer II/III and "atypical" pyramidal neurons in upper layer II showed regular spiking behavior, prominent frequency adaptation, and marked sAHPs. 5. In both layer I neurons and layer II

  2. Differential entrainment and learning-related dynamics of spike and local field potential activity in the sensorimotor and associative striatum.

    PubMed

    Thorn, Catherine A; Graybiel, Ann M

    2014-02-19

    Parallel cortico-basal ganglia loops are thought to have distinct but interacting functions in motor learning and habit formation. In rats, the striatal projection neuron populations (MSNs) in the dorsolateral and dorsomedial striatum, respectively corresponding to sensorimotor and associative regions of the striatum, exhibit contrasting dynamics as rats acquire T-maze tasks (Thorn et al., 2010). Here, we asked whether these patterns could be related to the activity of local interneuron populations in the striatum and to the local field potential activity recorded simultaneously in the corresponding regions. We found that dorsolateral and dorsomedial striatal fast-spiking interneurons exhibited task-specific and training-related dynamics consistent with those of corresponding MSN populations. Moreover, both MSNs and interneuron populations in both regions became entrained to theta-band (5-12 Hz) frequencies during task acquisition. However, the predominant entrainment frequencies were different for the sensorimotor and associative zones. Dorsolateral striatal neurons became entrained mid-task to oscillations centered ∼ 5 Hz, whereas simultaneously recorded neurons in the dorsomedial region became entrained to higher frequency (∼ 10 Hz) rhythms. These region-specific patterns of entrainment evolved dynamically with the development of region-specific patterns of interneuron and MSN activity, indicating that, with learning, these two striatal regions can develop different frequency-modulated circuit activities in parallel. We suggest that such differential entrainment of sensorimotor and associative neuronal populations, acquired through learning, could be critical for coordinating information flow throughout each trans-striatal network while simultaneously enabling nearby components of the separate networks to operate independently.

  3. Neonatal Tissue Damage Promotes Spike Timing-Dependent Synaptic Long-Term Potentiation in Adult Spinal Projection Neurons

    PubMed Central

    Li, Jie

    2016-01-01

    Mounting evidence from both humans and rodents suggests that tissue damage during the neonatal period can “prime” developing nociceptive pathways such that a subsequent injury during adulthood causes an exacerbated degree of pain hypersensitivity. However, the cellular and molecular mechanisms that underlie this priming effect remain poorly understood. Here, we demonstrate that neonatal surgical injury relaxes the timing rules governing long-term potentiation (LTP) at mouse primary afferent synapses onto mature lamina I projection neurons, which serve as a major output of the spinal nociceptive network and are essential for pain perception. In addition, whereas LTP in naive mice was only observed if the presynaptic input preceded postsynaptic firing, early tissue injury removed this temporal requirement and LTP was observed regardless of the order in which the inputs were activated. Neonatal tissue damage also reduced the dependence of spike-timing-dependent LTP on NMDAR activation and unmasked a novel contribution of Ca2+-permeable AMPARs. These results suggest for the first time that transient tissue damage during early life creates a more permissive environment for the production of LTP within adult spinal nociceptive circuits. This persistent metaplasticity may promote the excessive amplification of ascending nociceptive transmission to the mature brain and thereby facilitate the generation of chronic pain after injury, thus representing a novel potential mechanism by which early trauma can prime adult pain pathways in the CNS. SIGNIFICANCE STATEMENT Tissue damage during early life can “prime” developing nociceptive pathways in the CNS, leading to greater pain severity after repeat injury via mechanisms that remain poorly understood. Here, we demonstrate that neonatal surgical injury widens the timing window during which correlated presynaptic and postsynaptic activity can evoke long-term potentiation (LTP) at sensory synapses onto adult lamina I

  4. Consequences and mechanisms of spike broadening of R20 cells in Aplysia californica.

    PubMed

    Ma, M; Koester, J

    1995-10-01

    We studied frequency-dependent spike broadening in the two electrically coupled R20 neurons in the abdominal ganglion of Aplysia. The peptidergic R20 cells excite the R25/L25 interneurons (which trigger respiratory pumping) and inhibit the RB cells. When fired at 1-10 Hz, the duration of the falling phase of the action potential in R20 neurons increases 2-10 fold during a spike train. Spike broadening recorded from the somata of the R20 cells affected synaptic transmission to nearby follower cells. Chemically mediated synaptic output was reduced by approximately 50% when recorded trains of nonbroadened action potentials were used as command signals for a voltage-clamped R20 cell. Electrotonic EPSPs between the R20 cells, which normally facilitated by two- to fourfold during a high frequency spike train, showed no facilitation when spike broadening was prevented under voltage-clamp control. To examine the mechanism of frequency-dependent spike broadening, we applied two-electrode voltage-clamp and pharmacological techniques to the somata of R20 cells. Several voltage-gated ionic currents were isolated, including INa, a multicomponent ICa, and three K+ currents--a high threshold, fast transient A-type K+ current (IAdepol), a delayed rectifier K+ current (IK-V), and a Ca(2+)-sensitive K+ current (IK-Ca), made up of two components. The influences of different currents on spike broadening were determined by using the recorded train of gradually broadening action potentials as the command for the voltage clamp. We found the following. (1) IAdepol is the major outward current that contributes to repolarization of nonbroadened spikes. It undergoes pronounced cumulative inactivation that is a critical determinant of spike broadening. (2) Activity-dependent changes in IK-V, IK-Ca, and ICa have complex effects on the kinetics and extent of broadening. (3) The time integral of ICa during individual action potentials increases approximately threefold during spike broadening.

  5. Phage-display for identifying peptides that bind the spike protein of transmissible gastroenteritis virus and possess diagnostic potential

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The spike (S) protein is a key structural protein of coronaviruses including, the porcine transmissible gastroenteritis virus (TGEV). The S protein is a type I membrane glycoprotein located in the viral envelope and is responsible for mediating the binding of viral particles to specific cell recepto...

  6. 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.

  7. Propagation of Action Potentials: An Active Participation Exercise.

    ERIC Educational Resources Information Center

    Felsten, Gary

    1998-01-01

    Describes an active participation exercise that demonstrates the propagation of action potentials (the ability to transmit information through the neural network, dependent upon chemical interactions in the brain). Students assume the structure and function of the network by lining up around the room and communicating through hand signals and…

  8. Action potential and contraction of Dionaea muscipula (Venus flytrap).

    PubMed

    DI PALMA, J R; MOHL, R; BEST, W

    1961-03-24

    Observation of the action potential and contraction of the leaf of Dionaea muscipula Ellis revealed several interesting phenomena. Two successive stimuli are generally necessary to cause contraction. The first and ineffective stimulus is associated with slow depolarization. The second stimulus has much more rapid depolarization and initiates contraction.

  9. Passive Responses Resembling Action Potentials: A Device for the Classroom

    ERIC Educational Resources Information Center

    Newman, Ian A.; Pickard, Barbara G.

    1975-01-01

    Describes the construction and operation of a network of entirely passive electrical components that gives a response to an electrical shock similar to an action potential. The network of resistors, capacitors, and diodes was developed to produce responses that would mimic those observed, for example, when a dark-grown pea epicotyl is shocked…

  10. Stable propagation of synchronous spiking in cortical neural networks

    NASA Astrophysics Data System (ADS)

    Diesmann, Markus; Gewaltig, Marc-Oliver; Aertsen, Ad

    1999-12-01

    The classical view of neural coding has emphasized the importance of information carried by the rate at which neurons discharge action potentials. More recent proposals that information may be carried by precise spike timing have been challenged by the assumption that these neurons operate in a noisy fashion-presumably reflecting fluctuations in synaptic input-and, thus, incapable of transmitting signals with millisecond fidelity. Here we show that precisely synchronized action potentials can propagate within a model of cortical network activity that recapitulates many of the features of biological systems. An attractor, yielding a stable spiking precision in the (sub)millisecond range, governs the dynamics of synchronization. Our results indicate that a combinatorial neural code, based on rapid associations of groups of neurons co-ordinating their activity at the single spike level, is possible within a cortical-like network.

  11. 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

  12. 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.

  13. Sensory-Evoked Spiking Behavior Emerges via an Experience-Dependent Plasticity Mechanism.

    PubMed

    van Rheede, Joram J; Richards, Blake A; Akerman, Colin J

    2015-09-02

    The ability to generate action potentials (spikes) in response to synaptic input determines whether a neuron participates in information processing. How a developing neuron becomes an active participant in a circuit or whether this process is activity dependent is not known, especially as spike-dependent plasticity mechanisms would not be available to non-spiking neurons. Here we use the optic tectum of awake Xenopus laevis tadpoles to determine how a neuron becomes able to generate sensory-driven spikes in vivo. At the onset of vision, many tectal neurons do not exhibit visual spiking behavior, despite being intrinsically excitable and receiving visuotopically organized synaptic inputs. However, a brief period of visual stimulation can drive these neurons to start generating stimulus-driven spikes. This conversion relies upon a selective increase in glutamatergic input and requires depolarizing GABAergic transmission and NMDA receptor activation. This permissive form of experience-dependent plasticity enables a neuron to start contributing to circuit function.

  14. Natural Firing Patterns Imply Low Sensitivity of Synaptic Plasticity to Spike Timing Compared with Firing Rate.

    PubMed

    Graupner, Michael; Wallisch, Pascal; Ostojic, Srdjan

    2016-11-02

    Synaptic plasticity is sensitive to the rate and the timing of presynaptic and postsynaptic action potentials. In experimental protocols inducing plasticity, the imposed spike trains are typically regular and the relative timing between every presynaptic and postsynaptic spike is fixed. This is at odds with firing patterns observed in the cortex of intact animals, where cells fire irregularly and the timing between presynaptic and postsynaptic spikes varies. To investigate synaptic changes elicited by in vivo-like firing, we used numerical simulations and mathematical analysis of synaptic plasticity models. We found that the influence of spike timing on plasticity is weaker than expected from regular stimulation protocols. Moreover, when neurons fire irregularly, synaptic changes induced by precise spike timing can be equivalently induced by a modest firing rate variation. Our findings bridge the gap between existing results on synaptic plasticity and plasticity occurring in vivo, and challenge the dominant role of spike timing in plasticity.

  15. Ionic currents underlying the action potential of Rana pipiens oocytes.

    PubMed

    Schlichter, L C

    1989-07-01

    Ionic currents in immature, ovulated Rana pipiens oocytes (metaphase I) were studied using the voltage-clamp technique. At this stage of maturity the oocyte can produce action potentials in response to depolarizing current or as an "off response" to hyperpolarizing current. Reducing external Na+ to 1/10 normal (choline substituted) eliminated the action potentials and both the negative-slope region and zero-crossing of the I-V relation. Reducing external Cl- to 1/10 or 1/100 normal (methanesulfonate substituted) lengthened the action potential. The outward current was reduced and a net inward current was revealed. By changing external Na+, Cl-, and K+ concentrations and using blocking agents (SITS, TEA), three voltage- and time-dependent currents were identified, INa, IK and ICl. The Na+ current activated at about 0 mV and reversed at very positive values which decreased during maturation. Inward Na+ current produced the upstroke of the action potential. During each voltage-clamp step the Na+ current activated slowly (seconds) and did not inactivate within many minutes. The Na+ current was not blocked by TTX at micromolar concentrations. The K+ current was present only in the youngest oocytes. Because IK was superimposed on a large leakage current, it appeared to reverse at the resting potential. When leakage currents were subtracted, the reversal potential for IK was more negative than -110 mV in Ringer's solution. IK was outwardly rectifying and strongly activated above -50 mV. The outward K+ current produced an after hyperpolarization at the end of each action potential. IK was blocked completely and reversibly by 20 mM external TEA. The Cl- current activated at about +10 mV and was outwardly rectifying. ICl was blocked completely and reversibly by 400 microM SITS added to the bathing medium. This current helped repolarize the membrane following an action potential in the youngest oocytes and was the only repolarizing current in more mature oocytes that had lost

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

    PubMed Central

    Michalikova, Martina; 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. PMID:28068338

  17. Regenerating mammalian nerve fibres: changes in action potential waveform and firing characteristics following blockage of potassium conductance.

    PubMed

    Kocsis, J D; Waxman, S G; Hildebrand, C; Ruiz, J A

    1982-12-22

    Extracellular application of potassium channel blocking agents is known to increase the amplitude and duration of the compound action potential in non-myelinated and demyelinated axons, but not in mature mammalian myelinated fibres. In the present study we used intra-axonal and whole nerve recording techniques to study the effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on regenerating rat nerve fibres. Our results indicate that early regenerating (premyelinated) axons show considerable broadening of the action potential after 4-AP application and late regenerating (myelinated) axons give rise to burst activity following a single stimulus after 4-AP application. 4-AP did not affect spike waveform or firing properties of normal mature sciatic nerve fibres. These results demonstrate the importance of potassium conductance in stabilizing firing properties of myelinated regenerating axons.

  18. Action potential broadening induced by lithium may cause a presynaptic enhancement of excitatory synaptic transmission in neonatal rat hippocampus.

    PubMed

    Colino, A; García-Seoane, J J; Valentín, A

    1998-07-01

    Lithium enhances excitatory synaptic transmission in CA1 pyramidal cells, but the mechanisms remain unclear. The present study demonstrates that lithium enhances the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) receptor-mediated components of the excitatory postsynaptic current (EPSC). Lithium decreased the magnitude of paired-pulse facilitation and presented an inverse correlation between the lithium-induced enhancement of synaptic transmission and initial paired-pulse facilitation, which is consistent with a presynaptic mode of action. The enhancement of synaptic strength is likely to act, at least in part, by increasing the amplitude of the presynaptic Ca2+ transient. One mechanism which could account for this change of the presynaptic Ca2+ transient is an increase in the duration of the action potential. We investigated action potential in hippocampal pyramidal neurons and found that lithium (0.5-6 mM) increased the half-amplitude duration and reduced the rate of repolarization, whereas the rate of depolarization remained similar. To find out whether the lithium synaptic effects might be explained by spike broadening, we investigated the field recording of the excitatory postsynaptic potential (EPSP) in hippocampal slices and found three lines of evidence. First, the prolongation of the presynaptic action potential with 4-aminopyridine and tetraethylammonium blocked or reduced the synaptic effects of lithium. Second, the lithium-induced synaptic enhancement was modulated when presynaptic Ca2+ influx was varied by changing the external Ca2+ concentration. Finally, both effects, the synaptic transmission increment and the action potential broadening, were independent of inositol depletion. These results suggest that lithium enhances synaptic transmission in the hippocampus via a presynaptic site of action: the mechanism underlying the potentiating effect may be attributable to an increased Ca2+ influx consequent

  19. The spatio-temporal characteristics of action potential initiation in layer 5 pyramidal neurons: a voltage imaging study

    PubMed Central

    Popovic, Marko A; Foust, Amanda J; McCormick, David A; Zecevic, Dejan

    2011-01-01

    Abstract The spatial pattern of Na+ channel clustering in the axon initial segment (AIS) plays a critical role in tuning neuronal computations, and changes in Na+ channel distribution have been shown to mediate novel forms of neuronal plasticity in the axon. However, immunocytochemical data on channel distribution may not directly predict spatio-temporal characteristics of action potential initiation, and prior electrophysiological measures are either indirect (extracellular) or lack sufficient spatial resolution (intracellular) to directly characterize the spike trigger zone (TZ). We took advantage of a critical methodological improvement in the high sensitivity membrane potential imaging (Vm imaging) technique to directly determine the location and length of the spike TZ as defined in functional terms. The results show that in mature axons of mouse cortical layer 5 pyramidal cells, action potentials initiate in a region ∼20 μm in length centred between 20 and 40 μm from the soma. From this region, the AP depolarizing wave invades initial nodes of Ranvier within a fraction of a millisecond and propagates in a saltatory fashion into axonal collaterals without failure at all physiologically relevant frequencies. We further demonstrate that, in contrast to the saltatory conduction in mature axons, AP propagation is non-saltatory (monotonic) in immature axons prior to myelination. PMID:21669974

  20. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons

    PubMed Central

    Kimm, Tilia; Khaliq, Zayd M.

    2015-01-01

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency–current (f–I) relationship, whereas BK channel inhibition had little effect on the f–I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f–I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. SIGNIFICANCE STATEMENT This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra

  1. K+-induced twitch potentiation is not due to longer action potential.

    PubMed

    Yensen, Craig; Matar, Wadih; Renaud, Jean-Marc

    2002-07-01

    The objective of this study was to determine whether an increased duration of the action potential contributes to the K+-induced twitch potentiation at 37 degrees C. Twitch contractions were elicited by field stimulation, and action potentials were measured with conventional microelectrodes. For mouse extensor digitorum longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM (control). For soleus muscle, twitch force potentiation was observed between 7 and 11 mM K+. Time to peak and half-relaxation time were not affected by the increase in extracellular K+ concentration in EDL muscle, whereas both parameters became significantly longer in soleus muscle. Decrease in overshoot and prolongation of the action potential duration observed at 9 and 11 mM K+ were mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin (TTX; used to partially block Na+ channels). Despite similar action potentials, twitch force was not potentiated by TTX. It is therefore suggested that the K+-induced potentiation of the twitch in EDL muscle is not due to a prolongation of the action potential and contraction time, whereas a longer contraction, especially the relaxation phase, may contribute to the potentiation in soleus muscle.

  2. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.

    PubMed

    Jaffe, D B; Wang, B; Brenner, R

    2011-09-29

    The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca(2+) was high (>20 μM) and the other where BK-activating Ca(2+) was low (∼0.4-1.2 μM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We also found that depending on Ca(2+) dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.

  3. Functional Signature of Recovering Cortex: Dissociation of Local Field Potentials and Spiking Activity in Somatosensory Cortices of Spinal Cord Injured Monkeys

    PubMed Central

    Wang, Zheng; Qi, Hui-Xin; Kaas, Jon H.; Roe, Anna W.; Chen, Li Min

    2013-01-01

    After disruption of dorsal column afferents at high cervical spinal levels in adult monkeys, somatosensory cortical neurons recover responsiveness to tactile stimulation of the hand; this reactivation correlates with a recovery of hand use. However, it is not known if all neuronal response properties recover, and whether different cortical areas recover in a similar manner. To address this, we recorded neuronal activity in cortical area 3b and S2 in adult squirrel monkeys weeks after unilateral lesion of the dorsal columns. We found that in response to vibrotactile stimulation, local field potentials remained robust at all frequency ranges. However, neuronal spiking activity failed to follow at high frequencies (≥15Hz). We suggest that the failure to generate spiking activity at high stimulus frequency reflects a changed balance of inhibition and excitation in both area 3b and S2, and that this mismatch in spiking and local field potential is a signature of an early phase of recovering cortex (< two months). PMID:24017995

  4. 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

  5. Focused ultrasound effects on nerve action potential in vitro

    PubMed Central

    Colucci, Vincent; Strichartz, Gary; Jolesz, Ferenc; Vykhodtseva, Natalia; Hynynen, Kullervo

    2009-01-01

    Minimally invasive applications of thermal and mechanical energy to selective areas of the human anatomy have led to significant advances in treatment of and recovery from typical surgical interventions. Image-guided focused ultrasound allows energy to be deposited deep into the tissue, completely noninvasively. There has long been interest in using this focal energy delivery to block nerve conduction for pain control and local anesthesia. In this study, we have performed an in vitro study to further extend our knowledge of this potential clinical application. The sciatic nerves from the bullfrog (Rana catesbeiana) were subjected to focused ultrasound (at frequencies of 0.661MHz and 1.986MHz) and to heated Ringer’s solution. The nerve action potential was shown to decrease in the experiments and correlated with temperature elevation measured in the nerve. The action potential recovered either completely, partially, or not at all, depending on the parameters of the ultrasound exposure. The reduction of the baseline nerve temperature by circulating cooling fluid through the sonication chamber did not prevent the collapse of the nerve action potential; but higher power was required to induce the same endpoint as without cooling. These results indicate that a thermal mechanism of focused ultrasound can be used to block nerve conduction, either temporarily or permanently. PMID:19647923

  6. Action potential initiation and propagation in CA3 pyramidal axons.

    PubMed

    Meeks, Julian P; Mennerick, Steven

    2007-05-01

    Thin, unmyelinated axons densely populate the mammalian hippocampus and cortex. However, the location and dynamics of spike initiation in thin axons remain unclear. We investigated basic properties of spike initiation and propagation in CA3 neurons of juvenile rat hippocampus. Sodium channel alpha subunit distribution and local applications of tetrodotoxin demonstrate that the site of first threshold crossing in CA3 neurons is approximately 35 microm distal to the soma, somewhat more proximal than our previous estimates. This discrepancy can be explained by the finding, obtained with simultaneous whole cell somatic and extracellular axonal recordings, that a zone of axon stretching to approximately 100 microm distal to the soma reaches a maximum rate of depolarization nearly synchronously by the influx of sodium from the high-density channels. Models of the proximal axon incorporating observed distributions of sodium channel staining recapitulated salient features of somatic and axonal spike waveforms, including the predicted initiation zone, characteristic spike latencies, and conduction velocity. The preferred initiation zone was unaltered by stimulus strength or repetitive spiking, but repetitive spiking increased threshold and significantly slowed initial segment recruitment time and conduction velocity. Our work defines the dynamics of initiation and propagation in hippocampal principal cell axons and may help reconcile recent controversies over initiation site in other axons.

  7. 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

  8. Using extracellular action potential recordings to constrain compartmental models.

    PubMed

    Gold, Carl; Henze, Darrell A; Koch, Christof

    2007-08-01

    We investigate the use of extracellular action potential (EAP) recordings for biophysically faithful compartmental models. We ask whether constraining a model to fit the EAP is superior to matching the intracellular action potential (IAP). In agreement with previous studies, we find that the IAP method under-constrains the parameters. As a result, significantly different sets of parameters can have virtually identical IAP's. In contrast, the EAP method results in a much tighter constraint. We find that the distinguishing characteristics of the waveform--but not its amplitude-resulting from the distribution of active conductances are fairly invariant to changes of electrode position and detailed cellular morphology. Based on these results, we conclude that EAP recordings are an excellent source of data for the purpose of constraining compartmental models.

  9. Stability of Cardiac Action Potential Duration under Periodic Pacing.

    PubMed

    Xiaodong, Han; Hailang, Song; Xiaomei, Wu; Cuiwei, Yang; Zuxiang, Fang

    2005-01-01

    Action potential duration (APD) alternans is believed to be a loss of stability and contributes much to the reentry arrhythmias. The purpose of this study is to analyze the stability conditions for one-dimension model and higher dimension model. These criterions are concluded by linear stability analysis in nonlinear dynamics. They should be useful for finding of cardiac control algorithms in low energy defibrillation and the designing of antiarrhythmic drug.

  10. An Unsupervised Online Spike-Sorting Framework.

    PubMed

    Knieling, Simeon; Sridharan, Kousik S; Belardinelli, Paolo; Naros, Georgios; Weiss, Daniel; Mormann, Florian; Gharabaghi, Alireza

    2016-08-01

    Extracellular neuronal microelectrode recordings can include action potentials from multiple neurons. To separate spikes from different neurons, they can be sorted according to their shape, a procedure referred to as spike-sorting. Several algorithms have been reported to solve this task. However, when clustering outcomes are unsatisfactory, most of them are difficult to adjust to achieve the desired results. We present an online spike-sorting framework that uses feature normalization and weighting to maximize the distinctiveness between different spike shapes. Furthermore, multiple criteria are applied to either facilitate or prevent cluster fusion, thereby enabling experimenters to fine-tune the sorting process. We compare our method to established unsupervised offline (Wave_Clus (WC)) and online (OSort (OS)) algorithms by examining their performance in sorting various test datasets using two different scoring systems (AMI and the Adamos metric). Furthermore, we evaluate sorting capabilities on intra-operative recordings using established quality metrics. Compared to WC and OS, our algorithm achieved comparable or higher scores on average and produced more convincing sorting results for intra-operative datasets. Thus, the presented framework is suitable for both online and offline analysis and could substantially improve the quality of microelectrode-based data evaluation for research and clinical application.

  11. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons

    PubMed Central

    Nikitin, Evgeny S.; Bal, Natalia V.; Malyshev, Aleksey; Ierusalimsky, Victor N.; Spivak, Yulia; Balaban, Pavel M.; Volgushev, Maxim

    2017-01-01

    The ability of neocortical neurons to detect and encode rapid changes at their inputs is crucial for basic neuronal computations, such as coincidence detection, precise synchronization of activity and spike-timing dependent plasticity. Indeed, populations of cortical neurons can respond to subtle changes of the input very fast, on a millisecond time scale. Theoretical studies and model simulations linked the encoding abilities of neuronal populations to the fast onset dynamics of action potentials (APs). Experimental results support this idea, however mechanisms of fast onset of APs in cortical neurons remain elusive. Studies in neuronal cultures, that are allowing for accurate control over conditions of growth and microenvironment during the development of neurons and provide better access to the spike initiation zone, may help to shed light on mechanisms of AP generation and encoding. Here we characterize properties of AP encoding in neocortical neurons grown for 11–25 days in culture. We show that encoding of high frequencies improves upon culture maturation, which is accompanied by the development of passive electrophysiological properties and AP generation. The onset of APs becomes faster with culture maturation. Statistical analysis using correlations and linear model approaches identified the onset dynamics of APs as a major predictor of age-dependent changes of encoding. Encoding of high frequencies strongly correlated also with the input resistance of neurons. Finally, we show that maturation of encoding properties of neurons in cultures is similar to the maturation of encoding in neurons studied in slices. These results show that maturation of AP generators and encoding is, to a large extent, determined genetically and takes place even without normal micro-environment and activity of the whole brain in vivo. This establishes neuronal cultures as a valid experimental model for studying mechanisms of AP generation and encoding, and their maturation. PMID

  12. Characteristics of single large-conductance Ca2+-activated K+ channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus.

    PubMed

    Lin, Min; Hatcher, Jeff T; Wurster, Robert D; Chen, Qin-Hui; Cheng, Zixi Jack

    2014-01-15

    Large-conductance Ca2(+)-activated K+ channels (BK) regulate action potential (AP) properties and excitability in many central neurons. However, the properties and functional roles of BK channels in parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal 7-9 days. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. Using excised patch single-channel recordings, we identified voltage-gated and Ca(2+)-dependent BK channels in PCMNs. The majority of BK channels exhibited persistent channel opening during voltage holding. These BK channels had a conductance of 237 pS and a 50% opening probability at +27.9 mV, the channel open time constant was 3.37 ms at +20 mV, and dwell time increased exponentially as the membrane potential depolarized. At the +20-mV holding potential, the [Ca2+]50 was 15.2 μM with a P0.5 of 0.4. Occasionally, some BK channels showed a transient channel opening and fast inactivation. Using whole cell voltage clamp, we found that BK channel mediated outward currents and afterhyperpolarization currents (IAHP). Using whole cell current clamp, we found that application of BK channel blocker iberiotoxin (IBTX) increased spike half-width and suppressed fast afterhyperpolarization (fAHP) amplitude following single APs. In addition, IBTX application increased spike half-width and reduced the spike frequency-dependent AP broadening in trains and spike frequency adaption (SFA). Furthermore, BK channel blockade decreased spike frequency. Collectively, these results demonstrate that PCMNs have BK channels that significantly regulate AP repolarization, fAHP, SFA, and spike frequency. We conclude that activation of BK channels underlies one of the mechanisms for facilitation of PCMN excitability.

  13. Characteristics of single large-conductance Ca2+-activated K+ channels and their regulation of action potentials and excitability in parasympathetic cardiac motoneurons in the nucleus ambiguus

    PubMed Central

    Lin, Min; Hatcher, Jeff T.; Wurster, Robert D.; Chen, Qin-Hui

    2013-01-01

    Large-conductance Ca2+-activated K+ channels (BK) regulate action potential (AP) properties and excitability in many central neurons. However, the properties and functional roles of BK channels in parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) have not yet been well characterized. In this study, the tracer X-rhodamine-5 (and 6)-isothiocyanate (XRITC) was injected into the pericardial sac to retrogradely label PCMNs in FVB mice at postnatal 7–9 days. Two days later, XRITC-labeled PCMNs in brain stem slices were identified. Using excised patch single-channel recordings, we identified voltage-gated and Ca2+-dependent BK channels in PCMNs. The majority of BK channels exhibited persistent channel opening during voltage holding. These BK channels had a conductance of 237 pS and a 50% opening probability at +27.9 mV, the channel open time constant was 3.37 ms at +20 mV, and dwell time increased exponentially as the membrane potential depolarized. At the +20-mV holding potential, the [Ca2+]50 was 15.2 μM with a P0.5 of 0.4. Occasionally, some BK channels showed a transient channel opening and fast inactivation. Using whole cell voltage clamp, we found that BK channel mediated outward currents and afterhyperpolarization currents (IAHP). Using whole cell current clamp, we found that application of BK channel blocker iberiotoxin (IBTX) increased spike half-width and suppressed fast afterhyperpolarization (fAHP) amplitude following single APs. In addition, IBTX application increased spike half-width and reduced the spike frequency-dependent AP broadening in trains and spike frequency adaption (SFA). Furthermore, BK channel blockade decreased spike frequency. Collectively, these results demonstrate that PCMNs have BK channels that significantly regulate AP repolarization, fAHP, SFA, and spike frequency. We conclude that activation of BK channels underlies one of the mechanisms for facilitation of PCMN excitability. PMID:24196530

  14. Non-Hebbian spike-timing-dependent plasticity in cerebellar circuits

    PubMed Central

    Piochon, Claire; Kruskal, Peter; MacLean, Jason; Hansel, Christian

    2013-01-01

    Spike-timing-dependent plasticity (STDP) provides a cellular implementation of the Hebb postulate, which states that synapses, whose activity repeatedly drives action potential firing in target cells, are potentiated. At glutamatergic synapses onto hippocampal and neocortical pyramidal cells, synaptic activation followed by spike firing in the target cell causes long-term potentiation (LTP)—as predicted by Hebb—whereas excitatory postsynaptic potentials (EPSPs) evoked after a spike elicit long-term depression (LTD)—a phenomenon that was not specifically addressed by Hebb. In both instances the action potential in the postsynaptic target neuron is an instructive signal that is capable of supporting synaptic plasticity. STDP generally relies on the propagation of Na+ action potentials that are initiated in the axon hillhock back into the dendrite, where they cause depolarization and boost local calcium influx. However, recent studies in CA1 hippocampal pyramidal neurons have suggested that local calcium spikes might provide a more efficient trigger for LTP induction than backpropagating action potentials. Dendritic calcium spikes also play a role in an entirely different type of STDP that can be observed in cerebellar Purkinje cells. These neurons lack backpropagating Na+ spikes. Instead, plasticity at parallel fiber (PF) to Purkinje cell synapses depends on the relative timing of PF-EPSPs and activation of the glutamatergic climbing fiber (CF) input that causes dendritic calcium spikes. Thus, the instructive signal in this system is externalized. Importantly when EPSPs are elicited before CF activity, PF-LTD is induced rather than LTP. Thus, STDP in the cerebellum follows a timing rule that is opposite to its hippocampal/neocortical counterparts. Regardless, a common motif in plasticity is that LTD/LTP induction depends on the relative timing of synaptic activity and regenerative dendritic spikes which are driven by the instructive signal. PMID:23335888

  15. Non-Hebbian spike-timing-dependent plasticity in cerebellar circuits.

    PubMed

    Piochon, Claire; Kruskal, Peter; Maclean, Jason; Hansel, Christian

    2012-01-01

    Spike-timing-dependent plasticity (STDP) provides a cellular implementation of the Hebb postulate, which states that synapses, whose activity repeatedly drives action potential firing in target cells, are potentiated. At glutamatergic synapses onto hippocampal and neocortical pyramidal cells, synaptic activation followed by spike firing in the target cell causes long-term potentiation (LTP)-as predicted by Hebb-whereas excitatory postsynaptic potentials (EPSPs) evoked after a spike elicit long-term depression (LTD)-a phenomenon that was not specifically addressed by Hebb. In both instances the action potential in the postsynaptic target neuron is an instructive signal that is capable of supporting synaptic plasticity. STDP generally relies on the propagation of Na(+) action potentials that are initiated in the axon hillhock back into the dendrite, where they cause depolarization and boost local calcium influx. However, recent studies in CA1 hippocampal pyramidal neurons have suggested that local calcium spikes might provide a more efficient trigger for LTP induction than backpropagating action potentials. Dendritic calcium spikes also play a role in an entirely different type of STDP that can be observed in cerebellar Purkinje cells. These neurons lack backpropagating Na(+) spikes. Instead, plasticity at parallel fiber (PF) to Purkinje cell synapses depends on the relative timing of PF-EPSPs and activation of the glutamatergic climbing fiber (CF) input that causes dendritic calcium spikes. Thus, the instructive signal in this system is externalized. Importantly when EPSPs are elicited before CF activity, PF-LTD is induced rather than LTP. Thus, STDP in the cerebellum follows a timing rule that is opposite to its hippocampal/neocortical counterparts. Regardless, a common motif in plasticity is that LTD/LTP induction depends on the relative timing of synaptic activity and regenerative dendritic spikes which are driven by the instructive signal.

  16. Spike-timing-dependent synaptic plasticity depends on dendritic location

    NASA Astrophysics Data System (ADS)

    Froemke, Robert C.; Poo, Mu-ming; Dan, Yang

    2005-03-01

    In the neocortex, each neuron receives thousands of synaptic inputs distributed across an extensive dendritic tree. Although postsynaptic processing of each input is known to depend on its dendritic location, it is unclear whether activity-dependent synaptic modification is also location-dependent. Here we report that both the magnitude and the temporal specificity of spike-timing-dependent synaptic modification vary along the apical dendrite of rat cortical layer 2/3 pyramidal neurons. At the distal dendrite, the magnitude of long-term potentiation is smaller, and the window of pre-/postsynaptic spike interval for long-term depression (LTD) is broader. The spike-timing window for LTD correlates with the window of action potential-induced suppression of NMDA (N-methyl-D-aspartate) receptors; this correlation applies to both their dendritic location-dependence and pharmacological properties. Presynaptic stimulation with partial blockade of NMDA receptors induced LTD and occluded further induction of spike-timing-dependent LTD, suggesting that NMDA receptor suppression underlies LTD induction. Computer simulation studies showed that the dendritic inhomogeneity of spike-timing-dependent synaptic modification leads to differential input selection at distal and proximal dendrites according to the temporal characteristics of presynaptic spike trains. Such location-dependent tuning of inputs, together with the dendritic heterogeneity of postsynaptic processing, could enhance the computational capacity of cortical pyramidal neurons.

  17. Ion channels generating complex spikes in cartwheel cells of the dorsal cochlear nucleus.

    PubMed

    Kim, Yuil; Trussell, Laurence O

    2007-02-01

    Cartwheel cells are glycinergic interneurons that modify somatosensory input to the dorsal cochlear nucleus. They are characterized by firing of mixtures of both simple and complex action potentials. To understand what ion channels determine the generation of these two types of spike waveforms, we recorded from cartwheel cells using the gramicidin perforated-patch technique in brain slices of mouse dorsal cochlear nucleus and applied channel-selective blockers. Complex spikes were distinguished by whether they arose directly from a negative membrane potential or later during a long depolarization. Ca(2+) channels and Ca(2+)-dependent K(+) channels were major determinants of complex spikes. Onset complex spikes required T-type and possibly R-type Ca(2+) channels and were shaped by BK and SK K(+) channels. Complex spikes arising later in a depolarization were dependent on P/Q- and L-type Ca(2+) channels as well as BK and SK channels. BK channels also contributed to fast repolarization of simple spikes. Simple spikes featured an afterdepolarization that is probably the trigger for complex spiking and is shaped by T/R-type Ca(2+) and SK channels. Fast spikes were dependent on Na(+) channels; a large persistent Na(+) current may provide a depolarizing drive for spontaneous activity in cartwheel cells. Thus the diverse electrical behavior of cartwheel cells is determined by the interaction of a wide variety of ion channels with a prominent role played by Ca(2+).

  18. The Characteristics of Action Potentials in Primo Vessels and the Effects of Acetylcholine Injection to the Action Potentials

    PubMed Central

    Cho, Seong Jin; Lim, Jaekwan; Yeon, Sun Hee; Kwon, O. Sang; Choi, Kwang-Ho; Choi, Sun-Mi; Ryu, Yeon-Hee

    2013-01-01

    In a previous study, we found that Primo vessels generate different action potentials in smooth muscles, but this study compared the pulse shape to distinguish the two tissues. Thus, a more sophisticated extracellular experiment was performed in this study using an acetylcholine injection; we then observed changes in the amplitude, FWHM (full width at half maximum), and period to explore Primo vessel function. A third type of pulse was recorded for Primo vessels. We observed fast depolarizing and repolarizing phases for this pulse. Further, its FWHM was 30 ms between smooth muscles and neurons. Acetylcholine affected only the period. The amplitude and FWHM were consistent after injection. Primo-vessels generated action potentials at twice the frequency after injection. From the results, we speculate that Primo-vessels perform a role in transferring signals in a different manner, which may be relevant for acupuncture treatment. PMID:23861710

  19. Neuronal spike train entropy estimation by history clustering.

    PubMed

    Watters, Nicholas; Reeke, George N

    2014-09-01

    Neurons send signals to each other by means of sequences of action potentials (spikes). Ignoring variations in spike amplitude and shape that are probably not meaningful to a receiving cell, the information content, or entropy of the signal depends on only the timing of action potentials, and because there is no external clock, only the interspike intervals, and not the absolute spike times, are significant. Estimating spike train entropy is a difficult task, particularly with small data sets, and many methods of entropy estimation have been proposed. Here we present two related model-based methods for estimating the entropy of neural signals and compare them to existing methods. One of the methods is fast and reasonably accurate, and it converges well with short spike time records; the other is impractically time-consuming but apparently very accurate, relying on generating artificial data that are a statistical match to the experimental data. Using the slow, accurate method to generate a best-estimate entropy value, we find that the faster estimator converges to this value more closely and with smaller data sets than many existing entropy estimators.

  20. Decision making and action implementation: evidence for an early visually triggered motor activation specific to potential actions.

    PubMed

    Tandonnet, Christophe; Garry, Michael I; Summers, Jeffery J

    2013-07-01

    To make a decision may rely on accumulating evidence in favor of one alternative until a threshold is reached. Sequential-sampling models differ by the way of accumulating evidence and the link with action implementation. Here, we tested a model's prediction of an early action implementation specific to potential actions. We assessed the dynamics of action implementation in go/no-go and between-hand choice tasks by transcranial magnetic stimulation of the motor cortex (single- or paired-pulse TMS; 3-ms interstimulus interval). Prior to implementation of the selected action, the amplitude of the motor evoked potential first increased whatever the visual stimulus but only for the hand potentially involved in the to-be-produced action. These findings suggest that visual stimuli can trigger an early motor activation specific to potential actions, consistent with race-like models with continuous transmission between decision making and action implementation.

  1. Estimating Extracellular Spike Waveforms from CA1 Pyramidal Cells with Multichannel Electrodes

    PubMed Central

    Molden, Sturla; Moldestad, Olve; Storm, Johan F.

    2013-01-01

    Extracellular (EC) recordings of action potentials from the intact brain are embedded in background voltage fluctuations known as the “local field potential” (LFP). In order to use EC spike recordings for studying biophysical properties of neurons, the spike waveforms must be separated from the LFP. Linear low-pass and high-pass filters are usually insufficient to separate spike waveforms from LFP, because they have overlapping frequency bands. Broad-band recordings of LFP and spikes were obtained with a 16-channel laminar electrode array (silicone probe). We developed an algorithm whereby local LFP signals from spike-containing channel were modeled using locally weighted polynomial regression analysis of adjoining channels without spikes. The modeled LFP signal was subtracted from the recording to estimate the embedded spike waveforms. We tested the method both on defined spike waveforms added to LFP recordings, and on in vivo-recorded extracellular spikes from hippocampal CA1 pyramidal cells in anaesthetized mice. We show that the algorithm can correctly extract the spike waveforms embedded in the LFP. In contrast, traditional high-pass filters failed to recover correct spike shapes, albeit produceing smaller standard errors. We found that high-pass RC or 2-pole Butterworth filters with cut-off frequencies below 12.5 Hz, are required to retrieve waveforms comparable to our method. The method was also compared to spike-triggered averages of the broad-band signal, and yielded waveforms with smaller standard errors and less distortion before and after the spike. PMID:24391714

  2. Information Encoding and Reconstruction from the Phase of Action Potentials

    PubMed Central

    Nadasdy, Zoltan

    2009-01-01

    Fundamental questions in neural coding are how neurons encode, transfer, and reconstruct information from the pattern of action potentials (APs) exchanged between different brain structures. We propose a general model of neural coding where neurons encode information by the phase of their APs relative to their subthreshold membrane oscillations. We demonstrate by means of simulations that AP phase retains the spatial and temporal content of the input under the assumption that the membrane potential oscillations are coherent across neurons and between structures and have a constant spatial phase gradient. The model explains many unresolved physiological observations and makes a number of concrete, testable predictions about the relationship between APs, local field potentials, and subthreshold membrane oscillations, and provides an estimate of the spatio-temporal precision of neuronal information processing. PMID:19668700

  3. Intracochlear and extracochlear ECAPs suggest antidromic action potentials.

    PubMed

    Miller, Charles A; Abbas, Paul J; Hay-McCutcheon, Marcia J; Robinson, Barbara K; Nourski, Kirill V; Jeng, Fuh-Cherng

    2004-12-01

    With experimental animals, the electrically evoked compound action potential (ECAP) can be recorded from multiple sites (e.g., round window, intracranial and intracochlear sites). However, human ECAPs are typically recorded from intracochlear electrodes of the implanted array. To bridge this difference, we obtained ECAPs from cats using both intracochlear and nerve-trunk recording sites. We also sought to determine how recording the site influences the acquired evoked potential and how those differences may provide insight into basic excitation properties. In the main experiment, ECAPs were recorded from four acutely deafened cats after implanting a Nucleus-style banded electrode array. Potentials were recorded from an electrode positioned on the nerve trunk and an intracochlear electrode. We manipulated stimulus level, electrode configuration (monopolar vs bipolar) and stimulus polarity, variables that influence the site of excitation. Intracochlear ECAPs were found to be an order of magnitude greater than those obtained with the nerve-trunk electrode. Also, compared with the nerve-trunk potentials, the intracochlear ECAPs more closely resembled those obtained from humans in that latencies were shorter and the waveform morphology was typically biphasic (a negative peak followed by a positive peak). With anodic monophasic stimuli, the ECAP had a unique positive-to-negative morphology which we attributed to antidromic action potentials resulting from a relatively central site of excitation. We also collected intracochlear ECAPs from twenty Nucleus 24 implant users. Compared with the feline ECAPs, the human potentials had smaller amplitudes and longer latencies. It is not clear what underlies these differences, although several factors are considered.

  4. Action currents, internodal potentials, and extracellular records of myelinated mammalian nerve fibers derived from node potentials.

    PubMed Central

    Marks, W B; Loeb, G E

    1976-01-01

    The potential distribution within the internodal axon of mammalian nerve fibers is derived by applying known node potential waveforms to the ends of an equivalent circuit model of the internode. The complete spatial/temporal profile of action potentials synthesized from the internodal profiles is used to compute the node current waveforn, and the extracellular action potential around fibers captured within a tubular electrode. For amphibia, the results agreed with empirical values. For mammals, the amplitude of the node currents plotted against conduction velocity was fitted by a straight line. The extracellular potential waveform depended on the location of the nodes within the tube. For tubes of length from 2 to 8 internodes, extracellular wave amplitude (mammals) was about one-third of the product of peak node current and tube resistance (center to ends). The extracellular potentials developed by longitudinal and radial currents in an anisotropic medium (fiber bundle) are compared. PMID:1276389

  5. Optimization Methods for Spiking Neurons and Networks

    PubMed Central

    Russell, Alexander; Orchard, Garrick; Dong, Yi; Mihalaş, Ştefan; Niebur, Ernst; Tapson, Jonathan; Etienne-Cummings, Ralph

    2011-01-01

    Spiking neurons and spiking neural circuits are finding uses in a multitude of tasks such as robotic locomotion control, neuroprosthetics, visual sensory processing, and audition. The desired neural output is achieved through the use of complex neuron models, or by combining multiple simple neurons into a network. In either case, a means for configuring the neuron or neural circuit is required. Manual manipulation of parameters is both time consuming and non-intuitive due to the nonlinear relationship between parameters and the neuron’s output. The complexity rises even further as the neurons are networked and the systems often become mathematically intractable. In large circuits, the desired behavior and timing of action potential trains may be known but the timing of the individual action potentials is unknown and unimportant, whereas in single neuron systems the timing of individual action potentials is critical. In this paper, we automate the process of finding parameters. To configure a single neuron we derive a maximum likelihood method for configuring a neuron model, specifically the Mihalas–Niebur Neuron. Similarly, to configure neural circuits, we show how we use genetic algorithms (GAs) to configure parameters for a network of simple integrate and fire with adaptation neurons. The GA approach is demonstrated both in software simulation and hardware implementation on a reconfigurable custom very large scale integration chip. PMID:20959265

  6. Effects of odor stimulation on antidromic spikes in olfactory sensory neurons.

    PubMed

    Scott, John W; Sherrill, Lisa

    2008-12-01

    Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very

  7. Electrotonic and action potentials in the Venus flytrap.

    PubMed

    Volkov, Alexander G; Vilfranc, Chrystelle L; Murphy, Veronica A; Mitchell, Colee M; Volkova, Maia I; O'Neal, Lawrence; Markin, Vladislav S

    2013-06-15

    The electrical phenomena and morphing structures in the Venus flytrap have attracted researchers since the nineteenth century. We have observed that mechanical stimulation of trigger hairs on the lobes of the Venus flytrap induces electrotonic potentials in the lower leaf. Electrostimulation of electrical circuits in the Venus flytrap can induce electrotonic potentials propagating along the upper and lower leaves. The instantaneous increase or decrease in voltage of stimulating potential generates a nonlinear electrical response in plant tissues. Any electrostimulation that is not instantaneous, such as sinusoidal or triangular functions, results in linear responses in the form of small electrotonic potentials. The amplitude and sign of electrotonic potentials depend on the polarity and the amplitude of the applied voltage. Electrical stimulation of the lower leaf induces electrical signals, which resemble action potentials, in the trap between the lobes and the midrib. The trap closes if the stimulating voltage is above the threshold level of 4.4V. Electrical responses in the Venus flytrap were analyzed and reproduced in the discrete electrical circuit. The information gained from this study can be used to elucidate the coupling of intracellular and intercellular communications in the form of electrical signals within plants.

  8. Enhanced Burst-Suppression and Disruption of Local Field Potential Synchrony in a Mouse Model of Focal Cortical Dysplasia Exhibiting Spike-Wave Seizures

    PubMed Central

    Williams, Anthony J.; Zhou, Chen; Sun, Qian-Quan

    2016-01-01

    Focal cortical dysplasias (FCDs) are a common cause of brain seizures and are often associated with intractable epilepsy. Here we evaluated aberrant brain neurophysiology in an in vivo mouse model of FCD induced by neonatal freeze lesions (FLs) to the right cortical hemisphere (near S1). Linear multi-electrode arrays were used to record extracellular potentials from cortical and subcortical brain regions near the FL in anesthetized mice (5–13 months old) followed by 24 h cortical electroencephalogram (EEG) recordings. Results indicated that FL animals exhibit a high prevalence of spontaneous spike-wave discharges (SWDs), predominately during sleep (EEG), and an increase in the incidence of hyper-excitable burst/suppression activity under general anesthesia (extracellular recordings, 0.5%–3.0% isoflurane). Brief periods of burst activity in the local field potential (LFP) typically presented as an arrhythmic pattern of increased theta-alpha spectral peaks (4–12 Hz) on a background of low-amplitude delta activity (1–4 Hz), were associated with an increase in spontaneous spiking of cortical neurons, and were highly synchronized in control animals across recording sites in both cortical and subcortical layers (average cross-correlation values ranging from +0.73 to +1.0) with minimal phase shift between electrodes. However, in FL animals, cortical vs. subcortical burst activity was strongly out of phase with significantly lower cross-correlation values compared to controls (average values of −0.1 to +0.5, P < 0.05 between groups). In particular, a marked reduction in the level of synchronous burst activity was observed, the closer the recording electrodes were to the malformation (Pearson’s Correlation = 0.525, P < 0.05). In a subset of FL animals (3/9), burst activity also included a spike or spike-wave pattern similar to the SWDs observed in unanesthetized animals. In summary, neonatal FLs increased the hyperexcitable pattern of burst activity induced by

  9. Effects of 4-aminopyridine on action potentials generation in mouse sinoauricular node strips

    PubMed Central

    Golovko, Vladimir; Gonotkov, Mikhail; Lebedeva, Elena

    2015-01-01

    The physiological role of Ito has yet to be clarified. The goal of this study is to investigate the possible contribution of the transient outward current (Ito) on the generation of transmembrane action potentials (APs) and the sensitivity of mouse sinoauricular node (SAN) cells to a 4-aminopyridine (4AP) as Ito blocker. The electrophysiological identification of cells was performed in the sinoauricular node artery area (nstrips = 38) of the subendocardial surface using microelectrode technique. In this study, for the first time, it was observed that dependence duration of action potential at the level of 20% repolarization (APD20) level under a 4AP concentration in the pacemaker SAN and auricular cells corresponds to a curve predicted by Hill’s equation. APD20 raised by 70% and spike duration of AP increased by 15–25%, when 4AP concentration was increased from 0.1 to 5.0 mmol/L. Auricular cells were found to be more sensitive to 4AP than true pacemaker cells. This was accompanied by a decrease in the upstroke velocity as compared to the control. Our data and previous findings in the literature lead us to hypothesize that the 4AP-sensitive current participates in the repolarization formation of pacemaker and auricular type cells. Thus, study concerning the inhibitory effects of lidocaine and TTX on APD20 can explain the phenomenon of the decrease in upstroke velocity, which, for the first time, was observed after exposure to 4AP. Duration of AP at the level of 20% repolarization (APD20) under a 4-AP concentration 0.5 mmol/L in the true pacemaker cells lengthen by 60–70% with a control. PMID:26156968

  10. Optical Recording of Suprathreshold Neural Activity with Single-cell and Single-spike Resolution

    PubMed Central

    Ranganathan, Gayathri Nattar; Koester, Helmut J.

    2012-01-01

    Signaling of information in the vertebrate central nervous system is often carried by populations of neurons rather than individual neurons. Also propagation of suprathreshold spiking activity involves populations of neurons. Empirical studies addressing cortical function directly thus require recordings from populations of neurons with high resolution. Here we describe an optical method and a deconvolution algorithm to record neural activity from up to 100 neurons with single-cell and single-spike resolution. This method relies on detection of the transient increases in intracellular somatic calcium concentration associated with suprathreshold electrical spikes (action potentials) in cortical neurons. High temporal resolution of the optical recordings is achieved by a fast random-access scanning technique using acousto-optical deflectors (AODs)1. Two-photon excitation of the calcium-sensitive dye results in high spatial resolution in opaque brain tissue2. Reconstruction of spikes from the fluorescence calcium recordings is achieved by a maximum-likelihood method. Simultaneous electrophysiological and optical recordings indicate that our method reliably detects spikes (>97% spike detection efficiency), has a low rate of false positive spike detection (< 0.003 spikes/sec), and a high temporal precision (about 3 msec) 3. This optical method of spike detection can be used to record neural activity in vitro and in anesthetized animals in vivo3,4. PMID:22972033

  11. Uncertainty Propagation in Nerve Impulses Through the Action Potential Mechanism.

    PubMed

    Torres Valderrama, Aldemar; Witteveen, Jeroen; Navarro, Maria; Blom, Joke

    2015-12-01

    We investigate the propagation of probabilistic uncertainty through the action potential mechanism in nerve cells. Using the Hodgkin-Huxley (H-H) model and Stochastic Collocation on Sparse Grids, we obtain an accurate probabilistic interpretation of the deterministic dynamics of the transmembrane potential and gating variables. Using Sobol indices, out of the 11 uncertain parameters in the H-H model, we unravel two main uncertainty sources, which account for more than 90 % of the fluctuations in neuronal responses, and have a direct biophysical interpretation. We discuss how this interesting feature of the H-H model allows one to reduce greatly the probabilistic degrees of freedom in uncertainty quantification analyses, saving CPU time in numerical simulations and opening possibilities for probabilistic generalisation of other deterministic models of great importance in physiology and mathematical neuroscience.

  12. A web portal for in-silico action potential predictions

    PubMed Central

    Williams, Geoff; Mirams, Gary R.

    2015-01-01

    Introduction Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way of predicting the integrated compound effects on whole-cell electrophysiology, to provide an improved indication of pro-arrhythmic risk. Methods We have developed open source software to run cardiac electrophysiology simulations to predict the overall effect of compounds that block IKr, ICaL, INa, IKs, IK1 and Ito to varying degrees, using a choice of mathematical electrophysiology models. To enable safety pharmacology teams to run and evaluate these simulations easily, we have also developed an open source web portal interface to this simulator. Results The web portal can be found at https://chaste.cs.ox.ac.uk/ActionPotential. Users can enter details of compound affinities for ion channels in the form of IC50 or pIC50 values, run simulations, store the results for later retrieval, view summary graphs of the results, and export data to a spreadsheet format. Discussion This web portal provides a simple interface to reference versions of mathematical models, and well-tested state-of-the-art equation solvers. It provides safety teams easy access to the emerging technology of cardiac electrophysiology simulations for use in the drug-discovery process. PMID:25963830

  13. 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.

  14. Click- and chirp-evoked human compound action potentials.

    PubMed

    Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

    2010-05-01

    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.

  15. 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.

  16. Neural response dynamics of spiking and local field potential activity depend on CRT monitor refresh rate in the tree shrew primary visual cortex.

    PubMed

    Veit, Julia; Bhattacharyya, Anwesha; Kretz, Robert; Rainer, Gregor

    2011-11-01

    Entrainment of neural activity to luminance impulses during the refresh of cathode ray tube monitor displays has been observed in the primary visual cortex (V1) of humans and macaque monkeys. This entrainment is of interest because it tends to temporally align and thus synchronize neural responses at the millisecond timescale. Here we show that, in tree shrew V1, both spiking and local field potential activity are also entrained at cathode ray tube refresh rates of 120, 90, and 60 Hz, with weakest but still significant entrainment even at 120 Hz, and strongest entrainment occurring in cortical input layer IV. For both luminance increments ("white" stimuli) and decrements ("black" stimuli), refresh rate had a strong impact on the temporal dynamics of the neural response for subsequent luminance impulses. Whereas there was rapid, strong attenuation of spikes and local field potential to prolonged visual stimuli composed of luminance impulses presented at 120 Hz, attenuation was nearly absent at 60-Hz refresh rate. In addition, neural onset latencies were shortest at 120 Hz and substantially increased, by ∼15 ms, at 60 Hz. In terms of neural response amplitude, black responses dominated white responses at all three refresh rates. However, black/white differences were much larger at 60 Hz than at higher refresh rates, suggesting a mechanism that is sensitive to stimulus timing. Taken together, our findings reveal many similarities between V1 of macaque and tree shrew, while underscoring a greater temporal sensitivity of the tree shrew visual system.

  17. Kv2 channel regulation of action potential repolarization and firing patterns in superior cervical ganglion neurons and hippocampal CA1 pyramidal neurons.

    PubMed

    Liu, Pin W; Bean, Bruce P

    2014-04-02

    Kv2 family "delayed-rectifier" potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60-80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from -70 mV, but not -80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at -70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation.

  18. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    PubMed Central

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  19. The Potential of Deweyan-Inspired Action Research

    ERIC Educational Resources Information Center

    Stark, Jody L.

    2014-01-01

    In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

  20. Atrial cell action potential parameter fitting using genetic algorithms.

    PubMed

    Syed, Z; Vigmond, E; Nattel, S; Leon, L J

    2005-09-01

    Understanding of the considerable variation in action potential (AP) shape throughout the heart is necessary to explain normal and pathological cardiac function. Existing mathematical models reproduce typical APs, but not all measured APs, as fitting the sets of non-linear equations is a tedious process. The study describes the integration of a pre-existing mathematical model of an atrial cell AP with a genetic algorithm to provide an automated tool to generate APs for arbitrary cells by fitting ionic channel conductances. Using the Nygren model as the base, the technique was first verified by starting with random values and fitting the Nygren model to itself with an error of only 0.03%. The Courtemanche model, which has a different morphology from that of the Nygren model, was successfully fitted. The AP duration restitution curve generated by the fit matched that of the target model very well. Finally, experimentally recorded APs were reproduced. To match AP duration restitution behaviour properly, it was necessary simultaneously to fit over several stimulation frequencies. Also, fitting of the upstroke was better if the stimulating current pulse replicated that found in situ as opposed to a rectangular pulse. In conclusion, the modelled parameters were successfully able to reproduce any given atrial AP. This tool can be useful for determining parameters in new AP models, reproducing specific APs, as well as determining the locus of drug action by examining changes in conductance values.

  1. Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

    NASA Astrophysics Data System (ADS)

    Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

    2016-03-01

    Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

  2. Columnar specificity of microvascular oxygenation and blood flow response in primary visual cortex: evaluation by local field potential and spiking activity

    PubMed Central

    Wang, Zheng; Roe, Anna W

    2012-01-01

    The relation of cortical microcirculation, oxygen metabolism, and underlying neuronal network activity remains poorly understood. Anatomical distribution of cortical microvasculature and its relationship to cortical functional domains suggests that functional organizations may be revealed by mapping cerebral blood flow responses. However, there is little direct experimental evidence and a lack of electrophysiological evaluation. In this study, we mapped ocular-dominance columns in primary visual cortex (V1) of anesthetized macaques with capillary flow-based laser speckle contrast imaging and deoxyhemoglobin-based intrinsic optical imaging. In parallel, the local field potentials (LFPs) and spikes were recorded from a linear array of eight microelectrodes, carefully positioned into left and right eye columns in V1. We found differential activation maps of blood flow, after masking large superficial draining vessels, exhibited a column-like pattern similar as the oximetric maps. Both the activated spikes and γ-band LFP demonstrated corresponding eye preference, consistent with the imaging maps. Our results present direct support in favor of previous proposals that the regulation of microcirculation can be as fine as the submillimeter scale, suggesting that cortical vasculature is functionally organized at the columnar level in a manner appropriate for supplying energy demands of functionally specific neuronal populations. PMID:22027939

  3. Power-Law Dynamics of Membrane Conductances Increase Spiking Diversity in a Hodgkin-Huxley Model

    PubMed Central

    Teka, Wondimu; Stockton, David; Santamaria, Fidel

    2016-01-01

    We studied the effects of non-Markovian power-law voltage dependent conductances on the generation of action potentials and spiking patterns in a Hodgkin-Huxley model. To implement slow-adapting power-law dynamics of the gating variables of the potassium, n, and sodium, m and h, conductances we used fractional derivatives of order η≤1. The fractional derivatives were used to solve the kinetic equations of each gate. We systematically classified the properties of each gate as a function of η. We then tested if the full model could generate action potentials with the different power-law behaving gates. Finally, we studied the patterns of action potential that emerged in each case. Our results show the model produces a wide range of action potential shapes and spiking patterns in response to constant current stimulation as a function of η. In comparison with the classical model, the action potential shapes for power-law behaving potassium conductance (n gate) showed a longer peak and shallow hyperpolarization; for power-law activation of the sodium conductance (m gate), the action potentials had a sharp rise time; and for power-law inactivation of the sodium conductance (h gate) the spikes had wider peak that for low values of η replicated pituitary- and cardiac-type action potentials. With all physiological parameters fixed a wide range of spiking patterns emerged as a function of the value of the constant input current and η, such as square wave bursting, mixed mode oscillations, and pseudo-plateau potentials. Our analyses show that the intrinsic memory trace of the fractional derivative provides a negative feedback mechanism between the voltage trace and the activity of the power-law behaving gate variable. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron. PMID:26937967

  4. Spike history neural response model.

    PubMed

    Kameneva, Tatiana; Abramian, Miganoosh; Zarelli, Daniele; Nĕsić, Dragan; Burkitt, Anthony N; Meffin, Hamish; Grayden, David B

    2015-06-01

    There is a potential for improved efficacy of neural stimulation if stimulation levels can be modified dynamically based on the responses of neural tissue in real time. A neural model is developed that describes the response of neurons to electrical stimulation and that is suitable for feedback control neuroprosthetic stimulation. Experimental data from NZ white rabbit retinae is used with a data-driven technique to model neural dynamics. The linear-nonlinear approach is adapted to incorporate spike history and to predict the neural response of ganglion cells to electrical stimulation. To validate the fitness of the model, the penalty term is calculated based on the time difference between each simulated spike and the closest spike in time in the experimentally recorded train. The proposed model is able to robustly predict experimentally observed spike trains.

  5. Potential anti-inflammatory actions of the elmiric (lipoamino) acids

    PubMed Central

    Burstein, Sumner H.; Adams, Jeffrey K.; Bradshaw, Heather B.; Fraioli, Cristian; Rossetti, Ronald G.; Salmonsen, Rebecca A.; Shaw, John W.; Walker, J. Michael; Zipkin, Robert E.; Zurier, Robert B.

    2007-01-01

    A library of amino acid-fatty acid conjugates (elmiric acids) was synthesized and evaluated for activity as potential anti-inflammatory agents. The compounds were tested in vitro for their effects on cell proliferation and prostaglandin production and compared with their effects on in vivo models of inflammation. LPS stimulated RAW 267.4 mouse macrophage cells was the in vitro model and phorbol ester-induced mouse ear edema served as the principal in vivo model. The prostaglandin responses were found to be strongly dependent on the nature of the fatty acid part of the molecule. Polyunsaturated acid conjugates produced a marked increase in media levels of i15-deoxy-PGJ2 with minimal effects on PGE production. It is reported in the literature that prostaglandin ratios in which the J series predominates over the E series promote the resolution of inflammatory conditions. Several of the elmiric acids tested here produced such favorable ratios suggesting that their potential anti-inflammatory activity occurs via a novel mechanism of action. The ear edema assay results were generally in agreement with the prostaglandin assay findings indicating a connection between them. PMID:17383881

  6. Novel MEA platform with PDMS microtunnels enables the detection of action potential propagation from isolated axons in culture.

    PubMed

    Dworak, Bradley J; Wheeler, Bruce C

    2009-02-07

    This study investigated a novel multi-electrode-array (MEA) design capable of long-term and highly selective recordings of axonal signals using PDMS microtunnels. We successfully grew neurons in culture so that only axons extended through narrow (10 microm wide by 3 microm high) and long (750 microm) microtunnels under which multiple electrodes were integrated. This permitted the recording of relatively large (up to 200 microV) electrical signals, including the propagation speed and direction of these travelling action potentials. To further demonstrate the operation of the device as a diagnostic tool for drug screening assays, the drug mepivacaine was applied in washout experiments. Here, we identified significant changes in mean spiking rate and conduction velocity.

  7. A supercritical density of fast Na+ channels ensures rapid propagation of action potentials in GABAergic interneuron axons

    PubMed Central

    Hu, Hua; Jonas, Peter

    2014-01-01

    Fast-spiking, parvalbumin-expressing GABAergic interneurons/basket cells (BCs) play a key role in feedforward and feedback inhibition, gamma oscillations, and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. Here, we examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ~20 μm from the soma, and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block indicated that low axonal Na+ conductance density was sufficient for reliability, but high Na+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching, and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing. PMID:24657965

  8. Cellular mechanisms underlying spontaneous interictal spikes in an acute model of focal cortical epileptogenesis.

    PubMed

    de Curtis, M; Radici, C; Forti, M

    1999-01-01

    The cellular mechanisms involved in the generation of spontaneous epileptiform potentials were investigated in the pirifom cortex of the in vitro isolated guinea-pig brain. A single, unilateral injection of bicuculline (150-200 nmol) in the anterior piriform cortex induced locally spontaneous interictal spikes that recurred with a period of 8.81+/-4.47 s and propagated caudally to the ipsi- and contralateral hemispheres. Simultaneous extra- and intracellular recordings from layer II and III principal cells showed that the spontaneous interictal spike correlates to a burst of action potentials followed by a large afterdepolarization. Intracellular application of the sodium conductance blocker, QX-314 (80 mM), abolished bursting activity and unmasked a high-threshold slow spike enhanced by the calcium chelator EGTA (50 mM). The slow spike was abolished by membrane hyperpolarization and by local perfusion with 2 mM cadmium. The depolarizing potential that followed the primary burst was reduced by arterial perfusion with the N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (100-200 microM). The non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM), completely and reversibly blocked the spontaneous spikes. The interictal spikes were terminated by a large afterpotential blocked either by intracellular QX-314 (80 mM) or by extracellular application of phaclofen and 2-hydroxysaclofen (10 and 4 mM, respectively). The present study demonstrates that, in an acute model of epileptogenesis, spontaneous interictal spikes are fostered by a primary burst of fast action potentials that ride on a regenerative high-threshold, possibly calcium-mediated spike, which activates a recurrent, glutamate-mediated potential responsible for the entrainment of adjacent and remote cortical regions. The bursting activity is controlled by a GABA(B) receptor-mediated inhibitory synaptic potential.

  9. Mechanism of frequency-dependent broadening of molluscan neurone soma spikes.

    PubMed

    Aldrich, R W; Getting, P A; Thompson, S H

    1979-06-01

    1. Action potentials recorded from isolated dorid neurone somata increase in duration, i.e. broaden, during low frequency repetitive firing. Spike broadening is substantially reduced by external Co ions and implicates an inward Ca current. 2. During repetitive voltage clamp steps at frequencies slower than 1 Hz, in 100 mM-tetraethyl ammonium ions (TEA) inward Ca currents do not increase in amplitude. 3. Repetitive action potentials result in inactivation of delayed outward current. Likewise, repetitive voltage clamp steps which cause inactivation of delayed outward current also result in longer duration action potentials. 4. The frequency dependence of spike broadening and inactivation of the voltage dependent component (IK) of delayed outward current are similar. 5. Inactivation of IK is observed in all cells, however, only cells with relative large inward Ca currents show significant spike broadening. Spike broadening apparently results from the frequency dependent inactivation of IK which increases the expression of inward Ca current as a prominent shoulder on the repolarizing phase of the action potential. In addition, the presence of a prolonged Ca current increases the duration of the first action potential thereby allowing sufficient time for inactivation of IK.

  10. Channel noise effects on first spike latency of a stochastic Hodgkin-Huxley neuron

    NASA Astrophysics Data System (ADS)

    Maisel, Brenton; Lindenberg, Katja

    2017-02-01

    While it is widely accepted that information is encoded in neurons via action potentials or spikes, it is far less understood what specific features of spiking contain encoded information. Experimental evidence has suggested that the timing of the first spike may be an energy-efficient coding mechanism that contains more neural information than subsequent spikes. Therefore, the biophysical features of neurons that underlie response latency are of considerable interest. Here we examine the effects of channel noise on the first spike latency of a Hodgkin-Huxley neuron receiving random input from many other neurons. Because the principal feature of a Hodgkin-Huxley neuron is the stochastic opening and closing of channels, the fluctuations in the number of open channels lead to fluctuations in the membrane voltage and modify the timing of the first spike. Our results show that when a neuron has a larger number of channels, (i) the occurrence of the first spike is delayed and (ii) the variation in the first spike timing is greater. We also show that the mean, median, and interquartile range of first spike latency can be accurately predicted from a simple linear regression by knowing only the number of channels in the neuron and the rate at which presynaptic neurons fire, but the standard deviation (i.e., neuronal jitter) cannot be predicted using only this information. We then compare our results to another commonly used stochastic Hodgkin-Huxley model and show that the more commonly used model overstates the first spike latency but can predict the standard deviation of first spike latencies accurately. We end by suggesting a more suitable definition for the neuronal jitter based upon our simulations and comparison of the two models.

  11. Inhibition Potentiates the Synchronizing Action of Electrical Synapses

    PubMed Central

    Pfeuty, Benjamin; Golomb, David; Mato, Germán; Hansel, David

    2007-01-01

    In vivo and in vitro experimental studies have found that blocking electrical interactions connecting GABAergic interneurons reduces oscillatory activity in the γ range in cortex. However, recent theoretical works have shown that the ability of electrical synapses to promote or impede synchrony, when alone, depends on their location on the dendritic tree of the neurons, the intrinsic properties of the neurons and the connectivity of the network. The goal of the present paper is to show that this versatility in the synchronizing ability of electrical synapses is greatly reduced when the neurons also interact via inhibition. To this end, we study a model network comprising two-compartment conductance-based neurons interacting with both types of synapses. We investigate the effect of electrical synapses on the dynamical state of the network as a function of the strength of the inhibition. We find that for weak inhibition, electrical synapses reinforce inhibition-generated synchrony only if they promote synchrony when they are alone. In contrast, when inhibition is sufficiently strong, electrical synapses improve synchrony even if when acting alone they would stabilize asynchronous firing. We clarify the mechanism underlying this cooperative interplay between electrical and inhibitory synapses. We show that it is relevant in two physiologically observed regimes: spike-to-spike synchrony, where neurons fire at almost every cycle of the population oscillations, and stochastic synchrony, where neurons fire irregularly and at a rate which is substantially lower than the frequency of the global population rhythm. PMID:18946530

  12. Spike voltage topography in temporal lobe epilepsy.

    PubMed

    Asadi-Pooya, Ali A; Asadollahi, Marjan; Shimamoto, Shoichi; Lorenzo, Matthew; Sperling, Michael R

    2016-07-15

    We investigated the voltage topography of interictal spikes in patients with temporal lobe epilepsy (TLE) to see whether topography was related to etiology for TLE. Adults with TLE, who had epilepsy surgery for drug-resistant seizures from 2011 until 2014 at Jefferson Comprehensive Epilepsy Center were selected. Two groups of patients were studied: patients with mesial temporal sclerosis (MTS) on MRI and those with other MRI findings. The voltage topography maps of the interictal spikes at the peak were created using BESA software. We classified the interictal spikes as polar, basal, lateral, or others. Thirty-four patients were studied, from which the characteristics of 340 spikes were investigated. The most common type of spike orientation was others (186 spikes; 54.7%), followed by lateral (146; 42.9%), polar (5; 1.5%), and basal (3; 0.9%). Characteristics of the voltage topography maps of the spikes between the two groups of patients were somewhat different. Five spikes in patients with MTS had polar orientation, but none of the spikes in patients with other MRI findings had polar orientation (odds ratio=6.98, 95% confidence interval=0.38 to 127.38; p=0.07). Scalp topographic mapping of interictal spikes has the potential to offer different information than visual inspection alone. The present results do not allow an immediate clinical application of our findings; however, detecting a polar spike in a patient with TLE may increase the possibility of mesial temporal sclerosis as the underlying etiology.

  13. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    PubMed

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  14. Steroid inhibitors of androgen-potentiated actions on skin.

    PubMed

    Ebling, F J; Randall, V A

    1983-07-01

    Antiandrogens, such as cyproterone acetate, and oestrogens both inhibit sebaceous secretion in rats and have a potentiality for the treatment of hirsutism and acne in the human female. However, they act at different points. In castrated rats treated with testosterone, 3 micrograms/day oestradiol produced a greater decrease in sebum secretion than a dose of cyproterone acetate over 1000 times larger; moreover the antiandrogen reduced the incidence of sebaceous mitoses whereas the oestradiol did not. In hirsute women, oral administration of 100 mg of cyproterone acetate daily caused a 40% reduction in sebum secretion within 10 days; a further 20% was subsequently produced by combined therapy with cyproterone acetate and ethinyloestradiol. Significant decreases in the diameter and rate of growth of thigh hairs were not established until around the fourth monthly cycle of treatment. The actions were believed to be mainly peripheral, though contributory factors could also have been the small but significant reductions in plasma androgens produced by the antiandrogen, and the marked rise in sex hormone binding globulin produced by the oestrogen. That it is theoretically possible for cyproterone acetate or oestradiol to act locally follows from an unequivocal demonstration that either compound produced a local depression of sebum secretion when applied topically to rats.

  15. Ultrafast action potentials mediate kilohertz signaling at a central synapse.

    PubMed

    Ritzau-Jost, Andreas; Delvendahl, Igor; Rings, Annika; Byczkowicz, Niklas; Harada, Harumi; Shigemoto, Ryuichi; Hirrlinger, Johannes; Eilers, Jens; Hallermann, Stefan

    2014-10-01

    Fast synaptic transmission is important for rapid information processing. To explore the maximal rate of neuronal signaling and to analyze the presynaptic mechanisms, we focused on the input layer of the cerebellar cortex, where exceptionally high action potential (AP) frequencies have been reported in vivo. With paired recordings between presynaptic cerebellar mossy fiber boutons and postsynaptic granule cells, we demonstrate reliable neurotransmission up to ∼1 kHz. Presynaptic APs are ultrafast, with ∼100 μs half-duration. Both Kv1 and Kv3 potassium channels mediate the fast repolarization, rapidly inactivating sodium channels ensure metabolic efficiency, and little AP broadening occurs during bursts of up to 1.5 kHz. Presynaptic Cav2.1 (P/Q-type) calcium channels open efficiently during ultrafast APs. Furthermore, a subset of synaptic vesicles is tightly coupled to Ca(2+) channels, and vesicles are rapidly recruited to the release site. These data reveal mechanisms of presynaptic AP generation and transmitter release underlying neuronal kHz signaling.

  16. Short latency compound action potentials from mammalian gravity receptor organs

    NASA Technical Reports Server (NTRS)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  17. Bifurcation and Spike Adding Transition in Chay-Keizer Model

    NASA Astrophysics Data System (ADS)

    Lu, Bo; Liu, Shenquan; Liu, Xuanliang; Jiang, Xiaofang; Wang, Xiaohui

    Electrical bursting is an activity which is universal in excitable cells such as neurons and various endocrine cells, and it encodes rich physiological information. As burst delay identifies that the signal integration has reached the threshold at which it can generate an action potential, the number of spikes in a burst may have essential physiological implications, and the transition of bursting in excitable cells is associated with the bifurcation phenomenon closely. In this paper, we focus on the transition of the spike count per burst of the pancreatic β-cells within a mathematical model and bifurcation phenomenon in the Chay-Keizer model, which is utilized to simulate the pancreatic β-cells. By the fast-slow dynamical bifurcation analysis and the bi-parameter bifurcation analysis, the local dynamics of the Chay-Keizer system around the Bogdanov-Takens bifurcation is illustrated. Then the variety of the number of spikes per burst is discussed by changing the settings of a single parameter and bi-parameter. Moreover, results on the number of spikes within a burst are summarized in ISIs (interspike intervals) sequence diagrams, maximum and minimum, and the number of spikes under bi-parameter value changes.

  18. Effects of troglitazone and pioglitazone on the action potentials and membrane currents of rabbit ventricular myocytes.

    PubMed

    Ikeda, S; Watanabe, T

    1998-09-18

    The effects of the antidiabetic thiazolidinediones troglitazone and pioglitazone on action potentials and membrane currents were studied in rabbit ventricular myocytes. Troglitazone (10 microM) reversibly reduced excitability of the myocytes and modified their action potential configuration. It significantly increased the stimulation threshold required to elicit action potentials and decreased action potential amplitude and the maximum upstroke velocity of the action potentials. The Inhibition of the maximum upstroke velocity by troglitazone was also significant at 1 microM. Voltage-clamp experiments revealed that troglitazone (10 microM) reversibly inhibited both the slow inward Ca2+ current and the steady-state K+ current. In contrast to troglitazone, pioglitazone (1-10 microM) had no significant effect on the excitability, action potential configuration, or membrane currents of myocytes. These results suggest that troglitazone, but not pioglitazone, modulates Na+, Ca2+ and K+ currents, leading to the changes in excitability and action potential configuration of ventricular myocytes.

  19. Accumulation of recombinant SARS-CoV spike protein in plant cytosol and chloroplasts indicate potential for development of plant-derived oral vaccines.

    PubMed

    Li, Hong-Ye; Ramalingam, Sathishkumar; Chye, Mee-Len

    2006-09-01

    Plants are promising candidates as bioreactors for the production of oral recombinant proteins in the biopharmaceutical industry. As an initial step toward provision of an oral vaccine against the severe acute respiratory syndrome coronavirus (SARS-CoV), we have expressed a partial spike (S) protein of SARS-CoV in the cytosol of nuclear-transformed plants and in the chloroplasts of plastid-transformed plants. In the construction of both nuclear and plastid transformation vectors, a 2-kilobase nucleotide sequence encoding amino acids 1-658 of the SARS-CoV spike protein (S1) was modified with nucleotide changes, but not amino acid changes, to optimize codon usage for expression in plants. To investigate the subcellular localization of S1 during transient expression in tobacco leaves, a translational fusion consisting of S1 and the green fluorescent protein (GFP) was generated. Following agroinfiltration of tobacco leaves, analysis by laser confocal scanning microscopy revealed that the S1:GFP fusion protein was localized to the cytosol. In stable transgenic tobacco plants and lettuce plants generated by Agrobacterium-mediated transformation, tobacco and lettuce leaves were observed to express the S1 at high levels from the Cauliflower Mosaic Virus 35S promoter with Northern blot analysis. When the S1 was expressed in transplastomic tobacco, S1 messenger RNA and its corresponding protein were detected on Northern and Western blot analyses, respectively. Our results demonstrate the feasibility of producing S1 in nuclear- and chloroplast-transformed plants, indicating its potential in subsequent development of a plant-derived and safe oral recombinant subunit vaccine against the SARS-CoV in edible plants.

  20. Effects of neural refractoriness on spatio-temporal variability in spike initiations with Electrical stimulation.

    PubMed

    Mino, Hiroyuki; Rubinstein, Jay T

    2006-09-01

    In this paper, the effects of neural refractoriness on action potential (spike) initiations with electrical stimulation are investigated using computer modeling and simulation techniques. The computational model was composed of a myelinated nerve fiber with 50 nodes of Ranvier, each consisting of stochastic sodium and potassium channels, making it possible to represent the fluctuations of spike initiation. A series of two-pulse stimuli was presented by a stimulating electrode above the central (26th) node of Ranvier. The amplitude of the first (masker) pulse stimulus was set such that the masker pulse stimulus evoked spikes on each trial, while that of the second (probe) pulse stimulus was set such that the probe pulse stimulus evoked spikes on a half of trials, threshold values. Then the transmembrane potentials in response to the probe pulse stimulus were recorded at each node (i.e., 1-50 nodes) in order to determine the spike initiation node and time. From the observation of the spike initiation node and time, a spatio-temporal histogram as well as a spatial variability and a temporal variability of spike initiations was generated which allowed us to interpret fluctuations in spike initiation node and time. It was shown that the distribution of spike initiations tended to become greater spatially and longer temporally as the masker-probe intervals (MPIs) of the two-pulse stimuli shortened. It was also shown that the number of activated sodium channels as functions of space and time tended to become smaller due to inactivation of sodium channels and varied spatially and temporally as MPIs shortened. These findings may imply that the stochastic sodium channels during a relative refractory period may contribute to enhancing the fluctuations in spike initiations, and give us an insight into encoding information with electric stimuli to improve the performance of the prosthetic devices, especially cochlear implants.

  1. Recording Single Neurons' Action Potentials from Freely Moving Pigeons Across Three Stages of Learning

    PubMed Central

    Güntürkün, Onur

    2014-01-01

    While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.1 for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning. PMID:24961391

  2. Action-potential duration and the modulation of transmitter release from the sensory neurons of Aplysia in presynaptic facilitation and behavioral sensitization.

    PubMed

    Hochner, B; Klein, M; Schacher, S; Kandel, E R

    1986-11-01

    Presynaptic facilitation of transmitter release from Aplysia sensory neurons is an important contributor to behavioral sensitization of the gill and siphon withdrawal reflex. The enhanced release is accompanied by reduction of the serotonin-sensitive S current in the sensory neurons and a consequent increase in duration of the presynaptic action potential (ranging from 10% to 30%). We find that changes of similar magnitude in the duration of depolarizing voltage-clamp steps in sensory neurons in intact abdominal ganglia yield increases in synaptic potentials of 45-120%. In dissociated cell culture, these changes lead to increases of 25-60% in the synaptic potential. Prolongation of presynaptic depolarization using voltage clamp or prolongation of the duration of the action potential by K(+)-channel blockers leads to prolongation of the time-to-peak of the synaptic potentials; similar changes in time-to-peak occur during presynaptic facilitation. The time-to-peak is not changed by homosynaptic depression or by changing the Ca(2+) concentration, procedures that alter release without changing the duration of the action potential. Preventing the spike from broadening by voltage clamping the presynaptic neuron substantially reduces or blocks the facilitation. These results suggest that broadening of the action potential during facilitation is a causal factor in the enhancement of transmitter release.

  3. Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

    PubMed

    Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

    2008-02-01

    Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

  4. The impact of synaptic conductance on action potential waveform: evoking realistic action potentials with a simulated synaptic conductance.

    PubMed

    Johnston, Jamie; Postlethwaite, Michael; Forsythe, Ian D

    2009-10-15

    Most current clamp studies trigger action potentials (APs) by step current injection through the recording electrode and assume that the resulting APs are essentially identical to those triggered by orthodromic synaptic inputs. However this assumption is not always valid, particularly when the synaptic conductance is of large magnitude and of close proximity to the axon initial segment. We addressed this question of similarity using the Calyx of Held/MNTB synapse; we compared APs evoked by long duration step current injections, short step current injections and orthodromic synaptic stimuli. Neither injected current protocol evoked APs that matched the evoked orthodromic AP waveform, showing differences in AP height, half-width and after-hyperpolarization. We postulated that this 'error' could arise from changes in the instantaneous conductance during the combined synaptic and AP waveforms, since the driving forces for the respective ionic currents are integrating and continually evolving over this time-course. We demonstrate that a simple Ohm's law manipulation of the EPSC waveform, which accounts for the evolving driving force on the synaptic conductance during the AP, produces waveforms that closely mimic those generated by physiological synaptic stimulation. This stimulation paradigm allows supra-threshold physiological stimulation (single stimuli or trains) without the variability caused by quantal fluctuation in transmitter release, and can be implemented without a specialised dynamic clamp system. Combined with pharmacological tools this method provides a reliable means to assess the physiological roles of postsynaptic ion channels without confounding affects from the presynaptic input.

  5. BDNF Boosts Spike Fidelity in Chaotic Neural Oscillations

    PubMed Central

    Fujisawa, Shigeyoshi; Yamada, Maki K.; Nishiyama, Nobuyoshi; Matsuki, Norio; Ikegaya, Yuji

    2004-01-01

    Oscillatory activity and its nonlinear dynamics are of fundamental importance for information processing in the central nervous system. Here we show that in aperiodic oscillations, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, enhances the accuracy of action potentials in terms of spike reliability and temporal precision. Cultured hippocampal neurons displayed irregular oscillations of membrane potential in response to sinusoidal 20-Hz somatic current injection, yielding wobbly orbits in the phase space, i.e., a strange attractor. Brief application of BDNF suppressed this unpredictable dynamics and stabilized membrane potential fluctuations, leading to rhythmical firing. Even in complex oscillations induced by external stimuli of 40 Hz (γ) on a 5-Hz (θ) carrier, BDNF-treated neurons generated more precisely timed spikes, i.e., phase-locked firing, coupled with θ-phase precession. These phenomena were sensitive to K252a, an inhibitor of tyrosine receptor kinases and appeared attributable to BDNF-evoked Na+ current. The data are the first indication of pharmacological control of endogenous chaos. BDNF diminishes the ambiguity of spike time jitter and thereby might assure neural encoding, such as spike timing-dependent synaptic plasticity. PMID:14990508

  6. Differential effects of K(+) channel blockers on frequency-dependent action potential broadening in supraoptic neurons.

    PubMed

    Hlubek, M D; Cobbett, P

    2000-09-15

    Recordings were made from magnocellular neuroendocrine cells dissociated from the supraoptic nucleus of the adult guinea pig to determine the role of voltage gated K(+) channels in controlling the duration of action potentials and in mediating frequency-dependent action potential broadening exhibited by these neurons. The K(+) channel blockers charybdotoxin (ChTx), tetraethylammonium (TEA), and 4-aminopyridine (4-AP) increased the duration of individual action potentials indicating that multiple types of K(+) channel are important in controlling action potential duration. The effect of these K(+) channel blockers was almost completely reversed by simultaneous blockade of voltage gated Ca(2+) channels with Cd(2+). Frequency-dependent action potential broadening was exhibited by these neurons during trains of action potentials elicited by membrane depolarizing current pulses presented at 10 Hz but not at 1 Hz. 4-AP but not ChTx or TEA inhibited frequency-dependent action potential broadening indicating that frequency-dependent action potential broadening is dependent on increasing steady-state inactivation of A-type K(+) channels (which are blocked by 4-AP). A model of differential contributions of voltage gated K(+) channels and voltage gated Ca(2+) channels to frequency-dependent action potential broadening, in which an increase of Ca(2+) current during each successive action potential is permitted as a result of the increasing steady-state inactivation of A-type K(+) channels, is presented.

  7. Ontogeny of Vestibular Compound Action Potentials in the Domestic Chicken

    PubMed Central

    M. Jones, Sherri

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of –0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately –25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6–P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 μV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ. PMID:11545229

  8. Ontogeny of vestibular compound action potentials in the domestic chicken

    NASA Technical Reports Server (NTRS)

    Jones, S. M.; Jones, T. A.

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  9. Input-output relation and energy efficiency in the neuron with different spike threshold dynamics.

    PubMed

    Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

    2015-01-01

    Neuron encodes and transmits information through generating sequences of output spikes, which is a high energy-consuming process. The spike is initiated when membrane depolarization reaches a threshold voltage. In many neurons, threshold is dynamic and depends on the rate of membrane depolarization (dV/dt) preceding a spike. Identifying the metabolic energy involved in neural coding and their relationship to threshold dynamic is critical to understanding neuronal function and evolution. Here, we use a modified Morris-Lecar model to investigate neuronal input-output property and energy efficiency associated with different spike threshold dynamics. We find that the neurons with dynamic threshold sensitive to dV/dt generate discontinuous frequency-current curve and type II phase response curve (PRC) through Hopf bifurcation, and weak noise could prohibit spiking when bifurcation just occurs. The threshold that is insensitive to dV/dt, instead, results in a continuous frequency-current curve, a type I PRC and a saddle-node on invariant circle bifurcation, and simultaneously weak noise cannot inhibit spiking. It is also shown that the bifurcation, frequency-current curve and PRC type associated with different threshold dynamics arise from the distinct subthreshold interactions of membrane currents. Further, we observe that the energy consumption of the neuron is related to its firing characteristics. The depolarization of spike threshold improves neuronal energy efficiency by reducing the overlap of Na(+) and K(+) currents during an action potential. The high energy efficiency is achieved at more depolarized spike threshold and high stimulus current. These results provide a fundamental biophysical connection that links spike threshold dynamics, input-output relation, energetics and spike initiation, which could contribute to uncover neural encoding mechanism.

  10. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

    ERIC Educational Resources Information Center

    Rodriguez-Falces, Javier

    2015-01-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

  11. Uniformity detector retinal ganglion cells fire complex spikes and receive only light-evoked inhibition.

    PubMed

    Sivyer, Benjamin; Taylor, W Rowland; Vaney, David I

    2010-03-23

    Retinal ganglion cells convey information by increasing their firing in response to an optimal visual stimulus or "trigger feature." However, one class of ganglion cell responds to changes in the visual scene by decreasing its firing. These cells, termed uniformity detectors in the rabbit retina, are encountered only rarely and the synaptic mechanisms underlying their unusual responses have not been investigated. In this study, patch-clamp recordings of uniformity detectors show that the action potentials underlying the maintained firing arise within "complex spikes." Both ON and OFF visual stimuli elicit only inhibitory synaptic input, the immediate effect of which is to suppress the maintained firing. However, this inhibition also alters the properties of the "renascent" spiking by increasing the amplitude of the spikes within each burst, suggesting that the effect may increase the efficacy of spike propagation and transmission.

  12. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

    PubMed Central

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.

    2015-01-01

    Neuron–astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (−astrocyte) within the same culture dish. −Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. SIGNIFICANCE STATEMENT Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform

  13. Hydrogen peroxide decelerates recovery of action potential after high-frequency fatigue in skeletal muscle.

    PubMed

    Oba, T; Ishikawa, T; Takaishi, T; Aoki, T; Yamaguchi, M

    2000-10-01

    Effects of reactive oxygen species (ROS), especially hydrogen peroxide (H(2)O(2)), on recovery of action potential by resting for 30 min after high-frequency fatigue were studied using frog skeletal muscle fibers. After stimulation at a frequency of 50 HZ for 2 min, the action potential amplitude was decreased by 14.5 mV from controls, and resting membrane was depolarized by 15.4 mV. Action potential duration was also prolonged by high-frequency stimulation (1.5 ms in controls to 2.6 ms). The high-frequency stimulation used here caused no muscle damage. The action potential was partially improved after a 30-min rest. Addition of catalase at 500 units/ml or H(2)O(2) at 0.5 mM to sartorius muscle did not alter any of the parameters of the action potential after high-frequency stimulation. Treatment with catalase accelerated post-fatigue recovery of the action potential. Application of H(2)O(2) delayed post-fatigue recovery of resting and action potentials. When added to detubulated toe muscle fibers, catalase no longer improved the attenuation of action potential induced by high-frequency stimulation, even after a 30-min rest. These findings suggest that removal of H(2)O(2) from transverse tubules is effective for post-fatigue recovery of action potential in skeletal muscle.

  14. Strategically positioned inhibitory synapses of axo-axonic cells potently control principal neuron spiking in the basolateral amygdala.

    PubMed

    Veres, Judit M; Nagy, Gergő Attila; Vereczki, Viktória Krisztina; Andrási, Tibor; Hájos, Norbert

    2014-12-03

    Axo-axonic cells (AACs) in cortical regions selectively innervate the axon initial segments (AISs) of principal cells (PCs), where the action potentials are generated. These GABAergic interneurons can alter the activity of PCs, but how the efficacy of spike control correlates with the number of output synapses remains unclear. Moreover, the relationship between the spatial distribution of GABAergic synapses and the action potential initiation site along the AISs is not well defined. Using paired recordings obtained in the mouse basolateral amygdala, we found that AACs powerfully inhibited or delayed the timing of PC spiking by 30 ms, if AAC output preceded PC spiking with no more than 80 ms. By correlating the number of synapses and the probability of spiking, we revealed that larger numbers of presynaptic AAC boutons giving rise to larger postsynaptic responses provided more effective inhibition of PC spiking. At least 10-12 AAC synapses, which could originate from 2-3 AACs on average, were necessary to veto the PC firing under our recording conditions. Furthermore, we determined that the threshold for the action potential generation along PC axons is the lowest between 20 and 40 μm from soma, which axonal segment received the highest density of GABAergic inputs. Single AACs preferentially innervated this narrow portion of the AIS where action potentials were generated with the highest likelihood, regardless of the number of synapses forming a given connection. Our results uncovered a fine organization of AAC innervation maximizing their inhibitory efficacy by strategically positioning synapses along the AISs.

  15. On the excitation of action potentials by protons and its potential implications for cholinergic transmission.

    PubMed

    Fillafer, Christian; Schneider, Matthias F

    2016-03-01

    One of the most conserved mechanisms for transmission of a nerve pulse across a synapse relies on acetylcholine (ACh). Ever since the Nobel Prize-winning works of Dale and Loewi, it has been assumed that ACh-subsequent to its action on a postsynaptic cell-is split into inactive by-products by acetylcholinesterase (AChE). Herein, the widespread assumption of inactivity of ACh's hydrolysis products is falsified. Excitable cells (Chara braunii internodes), which had previously been unresponsive to ACh, became ACh-sensitive in the presence of AChE. The latter was evidenced by a striking difference in cell membrane depolarization upon exposure to 10 mM intact ACh (∆V = -2 ± 5 mV) and its hydrolysate (∆V = 81 ± 19 mV), respectively, for 60 s. This pronounced depolarization, which also triggered action potentials, was clearly attributed to one of the hydrolysis products: acetic acid (∆V = 87 ± 9 mV at pH 4.0; choline ineffective in the range 1-10 mM). In agreement with our findings, numerous studies in the literature have reported that acids excite gels, lipid membranes, plant cells, erythrocytes, as well as neurons. Whether excitation of the postsynaptic cell in a cholinergic synapse is due to protons or due to intact ACh is a most fundamental question that has not been addressed so far.

  16. Ionic differences between somatic and axonal action potentials in snail giant neurones

    PubMed Central

    Wald, Flora

    1972-01-01

    1. The ionic requirements of the somatic and axonal action potentials of `H' neurones of the snail Cryptomphallus aspersa were studied using intracellular micro-electrodes. 2. The overshoot of the somatic action potential increased by 10 mV for a tenfold increase in [Ca2+]o. In calcium-free media the action potential decreased gradually to values of 50 to 90% of the control and they could be completely eliminated with 2 mM-EGTA. The maximum rate of rise also varied with [Ca2+]o. 3. After 2 hr in sodium-free solution the somatic action potential decreased 6% in overshoot and 24% in rate of rise. 4. The somatic action potential was not affected by TTX, 5 × 10-6 g/ml. Procaine, 18 mM, reduced its rate of rise but did not eliminate it whereas 30 mM-CoCl2 did. 5. The size of the axonal action potential increased with increased [Na+]o, but decreased with an increase in [Ca2+]o. 6. Procaine, 18 mM, abolished the axonal action potential whereas it was not affected by TTX, 5 × 10-6 g/ml., nor, usually, by 30 mM-CoCl2. 7. The results obtained by studying the compound action potential of the nerves were similar to those from axonal action potentials. 8. The possibility that the somatic action potential is mainly calcium dependent while the axonal action potential is mainly produced by sodium is discussed. PMID:5014099

  17. Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

    PubMed

    Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

    2015-07-01

    Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

  18. Potential effects of intrinsic heart pacemaker cell mechanisms on dysrhythmic cardiac action potential firing

    PubMed Central

    Yaniv, Yael; Tsutsui, Kenta; Lakatta, Edward G.

    2015-01-01

    The heart's regular electrical activity is initiated by specialized cardiac pacemaker cells residing in the sinoatrial node. The rate and rhythm of spontaneous action potential firing of sinoatrial node cells are regulated by stochastic mechanisms that determine the level of coupling of chemical to electrical clocks within cardiac pacemaker cells. This coupled-clock system is modulated by autonomic signaling from the brain via neurotransmitter release from the vagus and sympathetic nerves. Abnormalities in brain-heart clock connections or in any molecular clock activity within pacemaker cells lead to abnormalities in the beating rate and rhythm of the pacemaker tissue that initiates the cardiac impulse. Dysfunction of pacemaker tissue can lead to tachy-brady heart rate alternation or exit block that leads to long atrial pauses and increases susceptibility to other cardiac arrhythmia. Here we review evidence for the idea that disturbances in the intrinsic components of pacemaker cells may be implemented in arrhythmia induction in the heart. PMID:25755643

  19. [Phenibut potentiation of the therapeutic action of antiparkinson agents].

    PubMed

    Gol'dblat, Iu V; Lapin, I P

    1986-01-01

    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  20. The growth cones of Aplysia sensory neurons: Modulation by serotonin of action potential duration and single potassium channel currents.

    PubMed

    Belardetti, F; Schacher, S; Kandel, E R; Siegelbaum, S A

    1986-09-01

    Serotonin (5-HT) closes a specific K channel ("S") in the cell body of Aplysia sensory neurons, resulting in a slow excitatory postsynaptic potential and spike broadening. To determine whether the S channel is present and can be modulated in processes of the neuron other than the cell body, we studied the effects of 5-HT on growth cones of sensory neurons in culture by using the patch-clamp technique. Simultaneous application of 5-HT to the cell body and to the growth cones of sensory neurons produced, in both, a slow depolarization of approximately 5 mV. Also, 5-HT produced a lengthening of the duration of action potential in the growth cone and cell body by 20-30%. Similar effects were observed in isolated growth cones that had been severed from the rest of the neuron, implying that the growth cones contain all the molecular components (i.e., receptors, channels, cAMP cascade) necessary for 5-HT action. Cell-attached patch-clamp recordings demonstrated the presence of S channels in sensory neuron growth cones. Application of serotonin to the bath produced long-lasting all-or-none closures of these channels in a manner identical to the previously characterized action of 5-HT in the cell body. Thus, channel modulation is not restricted to the cell body and probably occurs throughout the sensory neuron. This strengthens the view that S-channel modulation may also occur at the sensory neuron presynaptic terminal, where it could play a role in the presynaptic facilitation produced by 5-HT.

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

    PubMed

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

    2017-02-28

    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.

  2. Antimalarial action of hydroxamate-based iron chelators and potentiation of desferrioxamine action by reversed siderophores.

    PubMed Central

    Golenser, J; Tsafack, A; Amichai, Y; Libman, J; Shanzer, A; Cabantchik, Z I

    1995-01-01

    Hydroxamate-based chelators of iron are potent inhibitors of in vitro growth of Plasmodium falciparum. Two types of such chelators, the natural desferrioxamine and the synthetic reversed siderophore RSFileum2, are prototypes of antimalarial agents whose action spectra differ in the speed of action, stage dependence, and degree of reversibility of effects. This work explores the possibility of improving the antimalarial efficacy of these agents by using them in various combinations on in vitro cultures of P. falciparum. Growth assessment was based both on total nucleic acid synthesis and on parasitemia. The results indicate that the synthetic reversed siderophore more than complements the antimalarial action of desferrioxamine when applied during either ring, trophozoite, or mixed stages. The combined drug effects were significantly higher than the additive effect of the individual drugs. Qualitatively similar results were obtained for both reversible effects and irreversible (i.e., sustained) effects. Following an 8-h window of exposure the combined drug treatment caused parasite growth arrest and prevented its recovery, even 3 days after the treatment. The fact that such a combination of iron chelators displays a wider action spectrum than either drug alone has implications for the design of chemotherapy regimens. PMID:7695330

  3. Computer aided prediction and identification of potential epitopes in the receptor binding domain (RBD) of spike (S) glycoprotein of MERS-CoV.

    PubMed

    Ali, Mohammad Tuhin; Morshed, Mohammed Monzur; Gazi, Md Amran; Musa, Md Abu; Kibria, Md Golam; Uddin, Md Jashim; Khan, Md Anik Ashfaq; Hasan, Shihab

    2014-01-01

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) belongs to the coronaviridae family. In spite of several outbreaks in the very recent years, no vaccine against this deadly virus is developed yet. In this study, the receptor binding domain (RBD) of Spike (S) glycoprotein of MERS-CoV was analyzed through Computational Immunology approach to identify the antigenic determinants (epitopes). In order to do so, the sequences of S glycoprotein that belong to different geographical regions were aligned to observe the conservancy of MERS-CoV RBD. The immune parameters of this region were determined using different in silico tools and Immune Epitope Database (IEDB). Molecular docking study was also employed to check the affinity of the potential epitope towards the binding cleft of the specific HLA allele. The N-terminus RBD (S367-S606) of S glycoprotein was found to be conserved among all the available strains of MERS-CoV. Based on the lower IC50 value, a total of eight potential T-cell epitopes and 19 major histocompatibility complex (MHC) class-I alleles were identified for this conserved region. A 9-mer epitope CYSSLILDY displayed interactions with the maximum number of MHC class-I molecules and projected the highest peak in the B-cell antigenicity plot which concludes that it could be a better choice for designing an epitope based peptide vaccine against MERSCoV considering that it must undergo further in vitro and in vivo experiments. Moreover, in molecular docking study, this epitope was found to have a significant binding affinity of -8.5 kcal/mol towards the binding cleft of the HLA-C*12:03 molecule.

  4. Action potentials and twitch forces of rabbit masseter motor units at optimum jaw angle.

    PubMed

    van Eijden, T M G J; Turkawski, S J J

    2002-08-01

    This study examines mutual correlations between electrical and contractile motor-unit properties. Action potentials and twitch force responses of 42 masseter motor units were recorded in 14 rabbits. Motor units were excited by stimulating motoneurones in the trigeminal motor nucleus. Action potentials and twitches were measured at different jaw gapes between 0 and 21 degrees, in steps of 3 degrees. For each motor unit, the jaw angle-active force interrelation was determined and variables for action potential and force were compared at the jaw angle at which the motor unit produced the largest force. The results showed a large variation in variables for action potential and force, possibly related to the variation in motor-unit morphology. A weak correlation was found between the variables for action-potential amplitude and the magnitude of optimum force, indicating that motor units producing larger forces tended to have action potentials with larger amplitudes. Twitch-contraction time and the moment arm of the motor unit correlated positively with both the median frequency and the duration of the action potential. This indicates that slower contracting motor units had longer action potentials and is in accord with the earlier observation that slower motor units are preferentially located in the anterior regions of the masseter.

  5. A memristive spiking neuron with firing rate coding

    PubMed Central

    Ignatov, Marina; Ziegler, Martin; Hansen, Mirko; Petraru, Adrian; Kohlstedt, Hermann

    2015-01-01

    Perception, decisions, and sensations are all encoded into trains of action potentials in the brain. The relation between stimulus strength and all-or-nothing spiking of neurons is widely believed to be the basis of this coding. This initiated the development of spiking neuron models; one of today's most powerful conceptual tool for the analysis and emulation of neural dynamics. The success of electronic circuit models and their physical realization within silicon field-effect transistor circuits lead to elegant technical approaches. Recently, the spectrum of electronic devices for neural computing has been extended by memristive devices, mainly used to emulate static synaptic functionality. Their capabilities for emulations of neural activity were recently demonstrated using a memristive neuristor circuit, while a memristive neuron circuit has so far been elusive. Here, a spiking neuron model is experimentally realized in a compact circuit comprising memristive and memcapacitive devices based on the strongly correlated electron material vanadium dioxide (VO2) and on the chemical electromigration cell Ag/TiO2−x/Al. The circuit can emulate dynamical spiking patterns in response to an external stimulus including adaptation, which is at the heart of firing rate coding as first observed by E.D. Adrian in 1926. PMID:26539074

  6. Prolonged modification of action potential shape by synaptic inputs in molluscan neurones.

    PubMed

    Winlow, W

    1985-01-01

    1. Somatic action potentials of Lymnaea neurons are modified by excitatory or inhibitory synaptic inputs and have been studied using phase-plane techniques and an action potential duration monitor. 2. Excitatory synaptic inputs increase the rate of neuronal discharge, cause action potential broadening, a decrease in the maximum rate of depolarization (Vd) and a decrease in the maximum rate of repolarization (Vr). 3. Inhibitory synaptic inputs decrease the discharge rate and cause narrowing of action potentials, an increase in Vd and an increase in Vr. 4. The effects reported above outlast the original synaptic inputs by many seconds and, if the somatic action potentials are similar to those in the axon terminals, they may have far-reaching effects on transmitter release.

  7. Action potentials of isolated single muscle fibers recorded by potential-sensitive dyes

    PubMed Central

    Nakajima, S.; Gilai, A.

    1980-01-01

    Light transmission changes upon massive stimulation of single muscle fibers of Xenopus were studied with the potential-sensitive nonpermeant dyes, merocyanine rhodanine (WW375) and merocyanine oxazolone (NK2367). Upon stimulation an absorption change (wave a) occurred, which probably represents the sum of action potentials in the transverse tubules and surface membrane. In WW375-stained fibers wave a is a decrease in transmission over the range of 630 to 730 nm (with NK2367, over the range of 590 to 700 nm) but becomes an increase outside this range, thus showing a triphasic spectral pattern. This spectrum differs from that of the squid axon, in which depolarization produces only an increase in transmission over the whole range of wavelengths (Ross et al. 1977. J. Membr. Biol. 33:141-183). When wave a was measured at the edge of the fiber to obtain more signal from the surface membrane, the spectrum did not seem to differ markedly from that obtained from the entire width of the fiber. Thus, the difference in the spectrum between the squid axon and the vertebrate muscle cannot be attributed to the presence of the tubular system. PMID:10822501

  8. Excitation and Inhibition Compete to Control Spiking during Hippocampal Ripples: Intracellular Study in Behaving Mice

    PubMed Central

    English, Daniel F.; Peyrache, Adrien; Stark, Eran; Roux, Lisa; Vallentin, Daniela; Long, Michael A.

    2014-01-01

    High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation of the rhythm and the recruitment of spikes from pyramidal neurons are still poorly understood. Using intracellular, sharp electrode recordings in freely moving, drug-free mice, we observed consistent large depolarizations in CA1 pyramidal cells during sharp wave ripples, which are associated with ripple frequency fluctuation of the membrane potential (“intracellular ripple”). Despite consistent depolarization, often exceeding pre-ripple spike threshold values, current pulse-induced spikes were strongly suppressed, indicating that spiking was under the control of concurrent shunting inhibition. Ripple events were followed by a prominent afterhyperpolarization and spike suppression. Action potentials during and outside ripples were orthodromic, arguing against ectopic spike generation, which has been postulated by computational models of ripple generation. These findings indicate that dendritic excitation of pyramidal neurons during ripples is countered by shunting of the membrane and postripple silence is mediated by hyperpolarizing inhibition. PMID:25471587

  9. Epidermal laser stimulation of action potentials in the frog sciatic nerve

    NASA Astrophysics Data System (ADS)

    Jindra, Nichole M.; Goddard, Douglas; Imholte, Michelle; Thomas, Robert J.

    2010-01-01

    Measurements of laser-stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) are made using two infrared lasers. The dorsal sides of the frog's hind limbs are exposed to short-pulsed 1540- and 1064-nm wavelengths at three separate spot sizes: 2, 3, and 4 mm. Energy density thresholds are determined for eliciting an action potential at each experimental condition. Results from these exposures show similar evoked potential thresholds for both wavelengths. The 2-mm-diam spot sizes yield action potentials at radiant exposure levels almost double that seen with larger beam sizes.

  10. Genotoxic potential of glyphosate formulations: mode-of-action investigations.

    PubMed

    Heydens, William F; Healy, Charles E; Hotz, Kathy J; Kier, Larry D; Martens, Mark A; Wilson, Alan G E; Farmer, Donna R

    2008-02-27

    A broad array of in vitro and in vivo assays has consistently demonstrated that glyphosate and glyphosate-containing herbicide formulations (GCHF) are not genotoxic. Occasionally, however, related and contradictory data are reported, including findings of mouse liver and kidney DNA adducts and damage following intraperitoneal (ip) injection. Mode-of-action investigations were therefore undertaken to determine the significance of these contradictory data while concurrently comparing results from ip and oral exposures. Exposure by ip injection indeed produced marked hepatic and renal toxicity, but oral administration did not. The results suggest that ip injection of GCHF may induce secondary effects mediated by local toxicity rather than genotoxicity. Furthermore, these results continue to support the conclusion that glyphosate and GCHF are not genotoxic under exposure conditions that are relevant to animals and humans.

  11. Neuroactive steroids have multiple actions to potentiate GABAA receptors.

    PubMed

    Akk, Gustav; Bracamontes, John R; Covey, Douglas F; Evers, Alex; Dao, Tim; Steinbach, Joe Henry

    2004-07-01

    The effects of neuroactive steroids on the function of GABAA receptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with alpha1 beta2 gamma2L subunits. Activity was elicited with a half-maximal (50 microM) concentration of GABA. Two steroids were studied in detail: ACN ((3alpha,5alpha,17beta)-3-hydroxyandrostane-17-carbonitrile) and B285 ((3alpha,5beta,17beta)-3-hydroxy-18-norandrostane-17-carbonitrile). Four effects on channel activity were seen, two on open time distributions and two on closed times. When clusters of openings were elicited in the absence of steroid, the open time distribution contained three components. ACN produced concentration-dependent alterations in the open time distribution. The prevalence of the longest duration class of open times was increased from about 15% to about 40% (EC50 about 180 nM ACN), while the duration of the longest class increased from 7.4 ms to 27 ms (EC50 about 35 nM ACN). B285 also increased the prevalence of the longest duration open times (EC50 about 18 nM B285) but increased the duration only at concentrations close to 10 microM. The differences in the actions of these two steroids suggest that the effects on proportion and duration of the long duration open time component are produced by independent mechanisms and that there are separate recognition sites for the steroids which are associated with the two functional actions. The closed time distributions also showed three components in the absence of steroid. The rate of occurrence of the two brief duration closed time components decreased with increasing ACN, with an EC50 of about 50 nM ACN. In contrast, B285 did not reduce the rate of occurrence of the brief closings until high concentrations were applied. However, both B285 and ACN reduced the rate of occurrence of the activation-related closed state selectively, with comparable IC50 concentrations (about 40 nM ACN, 20 nM B285). As in the case for

  12. Neuronal communication: firing spikes with spikes.

    PubMed

    Brecht, Michael

    2012-08-21

    Spikes of single cortical neurons can exert powerful effects even though most cortical synapses are too weak to fire postsynaptic neurons. A recent study combining single-cell stimulation with population imaging has visualized in vivo postsynaptic firing in genetically identified target cells. The results confirm predictions from in vitro work and might help to understand how the brain reads single-neuron activity.

  13. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

    PubMed Central

    Crago, Patrick E; Makowski, Nathan S

    2014-01-01

    Objective Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main Results Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases.. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

  14. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

    NASA Astrophysics Data System (ADS)

    Crago, Patrick E.; Makowski, Nathaniel S.

    2014-10-01

    Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic

  15. Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

    NASA Astrophysics Data System (ADS)

    Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

    2004-05-01

    A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution—plotted as a current-arrow map (CAM)—calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter.

  16. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons

    PubMed Central

    Lee, Philip R.; Cohen, Jonathan E.; Iacobas, Dumitru A.; Iacobas, Sanda; Fields, R. Douglas

    2017-01-01

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life. PMID:28256583

  17. Gene networks activated by specific patterns of action potentials in dorsal root ganglia neurons.

    PubMed

    Lee, Philip R; Cohen, Jonathan E; Iacobas, Dumitru A; Iacobas, Sanda; Fields, R Douglas

    2017-03-03

    Gene regulatory networks underlie the long-term changes in cell specification, growth of synaptic connections, and adaptation that occur throughout neonatal and postnatal life. Here we show that the transcriptional response in neurons is exquisitely sensitive to the temporal nature of action potential firing patterns. Neurons were electrically stimulated with the same number of action potentials, but with different inter-burst intervals. We found that these subtle alterations in the timing of action potential firing differentially regulates hundreds of genes, across many functional categories, through the activation or repression of distinct transcriptional networks. Our results demonstrate that the transcriptional response in neurons to environmental stimuli, coded in the pattern of action potential firing, can be very sensitive to the temporal nature of action potential delivery rather than the intensity of stimulation or the total number of action potentials delivered. These data identify temporal kinetics of action potential firing as critical components regulating intracellular signalling pathways and gene expression in neurons to extracellular cues during early development and throughout life.

  18. Spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells.

    PubMed Central

    Jensen, M S; Azouz, R; Yaari, Y

    1996-01-01

    1. Intracellular recordings in adult rat hippocampal slices were used to investigate the properties and origins of intrinsically generated bursts in the somata of CA1 pyramidal cells (PCs). The CA1 PCs were classified as either non-bursters or bursters according to the firing patterns evoked by intrasomatically applied long ( > or = 100 ms) depolarizing current pulses. Non-bursters generated stimulus-graded trains of independent action potentials, whereas bursters generated clusters of three or more closely spaced spikes riding on a distinct depolarizing envelope. 2. In all PCs fast spike repolarization was incomplete and ended at a potential approximately 10 mV more positive than resting potential. Solitary spikes were followed by a distinct after-depolarizing potential (ADP) lasting 20-40 ms. The ADP in most non-bursters declined monotonically to baseline ('passive' ADP), whereas in most bursters it remained steady or even re-depolarized before declining to baseline ('active' ADP). 3. Active, but not passive, ADPs were associated with an apparent increase in input conductance. They were maximal in amplitude when the spike was evoked from resting potential and were reduced by mild depolarization or hyperpolarization (+/- 2 mV). 4. Evoked and spontaneous burst firing was sensitive to small changes in membrane potential. In most cases maximal bursts were generated at resting potential and were curtailed by small depolarizations or hyperpolarizations (+/- 5 mV). 5. Bursts comprising clusters of spikelets ('d-spikes') were observed in 12% of the bursters. Some of the d-spikes attained threshold for triggering full somatic spikes. Gradually hyperpolarizing these neurones blocked somatic spikes before blocking d-spikes, suggesting that the latter are generated at more remote sites. 6. The data suggest that active ADPs and intrinsic bursts in the somata of adult CA1 PCs are generated by a slow, voltage-gated inward current. Bursts arise in neurones in which this current

  19. Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle

    PubMed Central

    Cho, Seong-Jin; Lee, Sang-Hun; Zhang, Wenji; Lee, Sae-Bhom; Choi, Kwang-Ho; Choi, Sun-Mi; Ryu, Yeon-Hee

    2012-01-01

    We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid depolarizing and repolarizing phases, and (2) Type II pulse had a rapid depolarizing phase and a gradually slowing repolarizing phase. PMID:22319544

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

    NASA Astrophysics Data System (ADS)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    Objective. 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. Approach. 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. Main results. 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. Significance. 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.

  1. Repertoires of Spike Avalanches Are Modulated by Behavior and Novelty

    PubMed Central

    Ribeiro, Tiago L.; Ribeiro, Sidarta; Copelli, Mauro

    2016-01-01

    Neuronal avalanches measured as consecutive bouts of thresholded field potentials represent a statistical signature that the brain operates near a critical point. In theory, criticality optimizes stimulus sensitivity, information transmission, computational capability and mnemonic repertoires size. Field potential avalanches recorded via multielectrode arrays from cortical slice cultures are repeatable spatiotemporal activity patterns. It remains unclear whether avalanches of action potentials observed in forebrain regions of freely-behaving rats also form recursive repertoires, and whether these have any behavioral relevance. Here, we show that spike avalanches, recorded from hippocampus (HP) and sensory neocortex of freely-behaving rats, constitute distinct families of recursive spatiotemporal patterns. A significant number of those patterns were specific to a behavioral state. Although avalanches produced during sleep were mostly similar to others that occurred during waking, the repertoire of patterns recruited during sleep differed significantly from that of waking. More importantly, exposure to novel objects increased the rate at which new patterns arose, also leading to changes in post-exposure repertoires, which were significantly different from those before the exposure. A significant number of families occurred exclusively during periods of whisker contact with objects, but few were associated with specific objects. Altogether, the results provide original evidence linking behavior and criticality at the spike level: spike avalanches form repertoires that emerge in waking, recur during sleep, are diversified by novelty and contribute to object representation. PMID:27047341

  2. Repertoires of Spike Avalanches Are Modulated by Behavior and Novelty.

    PubMed

    Ribeiro, Tiago L; Ribeiro, Sidarta; Copelli, Mauro

    2016-01-01

    Neuronal avalanches measured as consecutive bouts of thresholded field potentials represent a statistical signature that the brain operates near a critical point. In theory, criticality optimizes stimulus sensitivity, information transmission, computational capability and mnemonic repertoires size. Field potential avalanches recorded via multielectrode arrays from cortical slice cultures are repeatable spatiotemporal activity patterns. It remains unclear whether avalanches of action potentials observed in forebrain regions of freely-behaving rats also form recursive repertoires, and whether these have any behavioral relevance. Here, we show that spike avalanches, recorded from hippocampus (HP) and sensory neocortex of freely-behaving rats, constitute distinct families of recursive spatiotemporal patterns. A significant number of those patterns were specific to a behavioral state. Although avalanches produced during sleep were mostly similar to others that occurred during waking, the repertoire of patterns recruited during sleep differed significantly from that of waking. More importantly, exposure to novel objects increased the rate at which new patterns arose, also leading to changes in post-exposure repertoires, which were significantly different from those before the exposure. A significant number of families occurred exclusively during periods of whisker contact with objects, but few were associated with specific objects. Altogether, the results provide original evidence linking behavior and criticality at the spike level: spike avalanches form repertoires that emerge in waking, recur during sleep, are diversified by novelty and contribute to object representation.

  3. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    PubMed

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  4. Inference of neuronal network spike dynamics and topology from calcium imaging data.

    PubMed

    Lütcke, Henry; Gerhard, Felipe; Zenke, Friedemann; Gerstner, Wulfram; Helmchen, Fritjof

    2013-01-01

    Two-photon calcium imaging enables functional analysis of neuronal circuits by inferring action potential (AP) occurrence ("spike trains") from cellular fluorescence signals. It remains unclear how experimental parameters such as signal-to-noise ratio (SNR) and acquisition rate affect spike inference and whether additional information about network structure can be extracted. Here we present a simulation framework for quantitatively assessing how well spike dynamics and network topology can be inferred from noisy calcium imaging data. For simulated AP-evoked calcium transients in neocortical pyramidal cells, we analyzed the quality of spike inference as a function of SNR and data acquisition rate using a recently introduced peeling algorithm. Given experimentally attainable values of SNR and acquisition rate, neural spike trains could be reconstructed accurately and with up to millisecond precision. We then applied statistical neuronal network models to explore how remaining uncertainties in spike inference affect estimates of network connectivity and topological features of network organization. We define the experimental conditions suitable for inferring whether the network has a scale-free structure and determine how well hub neurons can be identified. Our findings provide a benchmark for future calcium imaging studies that aim to reliably infer neuronal network properties.

  5. Inference of neuronal network spike dynamics and topology from calcium imaging data

    PubMed Central

    Lütcke, Henry; Gerhard, Felipe; Zenke, Friedemann; Gerstner, Wulfram; Helmchen, Fritjof

    2013-01-01

    Two-photon calcium imaging enables functional analysis of neuronal circuits by inferring action potential (AP) occurrence (“spike trains”) from cellular fluorescence signals. It remains unclear how experimental parameters such as signal-to-noise ratio (SNR) and acquisition rate affect spike inference and whether additional information about network structure can be extracted. Here we present a simulation framework for quantitatively assessing how well spike dynamics and network topology can be inferred from noisy calcium imaging data. For simulated AP-evoked calcium transients in neocortical pyramidal cells, we analyzed the quality of spike inference as a function of SNR and data acquisition rate using a recently introduced peeling algorithm. Given experimentally attainable values of SNR and acquisition rate, neural spike trains could be reconstructed accurately and with up to millisecond precision. We then applied statistical neuronal network models to explore how remaining uncertainties in spike inference affect estimates of network connectivity and topological features of network organization. We define the experimental conditions suitable for inferring whether the network has a scale-free structure and determine how well hub neurons can be identified. Our findings provide a benchmark for future calcium imaging studies that aim to reliably infer neuronal network properties. PMID:24399936

  6. Neural recording front-end IC using action potential detection and analog buffer with digital delay for data compression.

    PubMed

    Liu, Lei; Yao, Lei; Zou, Xiaodan; Goh, Wang Ling; Je, Minkyu

    2013-01-01

    This paper presents a neural recording analog front-end IC intended for simultaneous neural recording with action potential (AP) detection for data compression in wireless multichannel neural implants. The proposed neural recording front-end IC detects the neural spikes and sends only the preserved AP information for wireless transmission in order to reduce the overall power consumption of the neural implant. The IC consists of a low-noise neural amplifier, an AP detection circuit and an analog buffer with digital delay. The neural amplifier makes use of a current-reuse technique to maximize the transconductance efficiency for attaining a good noise efficiency factor. The AP detection circuit uses an adaptive threshold voltage to generate an enable signal for the subsequent functional blocks. The analog buffer with digital delay is employed using a finite impulse response (FIR) filter which preserves the AP waveform before the enable signal as well as provides low-pass filtering. The neural recording front-end IC has been designed using standard CMOS 0.18-µm technology occupying a core area of 220 µm by 820 µm.

  7. Antioxidant properties of melatonin and its potential action in diseases.

    PubMed

    Karaaslan, Cigdem; Suzen, Sibel

    2015-01-01

    In recent years, relationship between free radicals and oxidative stress with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases became increasingly clear. Confirming the role of oxidants in numerous pathological conditions such as cancer, the antioxidants developed as therapeutics have been proven ineffective. It is well established that melatonin (MLT) and its metabolites are able to function as endogenous free-radical scavengers and broadspectrum antioxidants. Numerous studies also proved the role of MLT and its derivatives in many physiological processes and therapeutic functions, such as the regulation of circadian rhythm and immune functions. The aim of this review is to arouse attention to MLT as a potentially valuable agent in the prevention and/or treatment of some diseases.

  8. Wheel-running exercise alters rat diaphragm action potentials and their regulation by K+ channels.

    PubMed

    Van Lunteren, Erik; Moyer, Michelle

    2003-08-01

    Endurance exercise modifies regulatory systems that control skeletal muscle Na+ and K+ fluxes, in particular Na+-K+-ATPase-mediated transport of these ions. Na+ and K+ ion channels also play important roles in the regulation of ionic movements, specifically mediating Na+ influx and K+ efflux that occur during contractions resulting from action potential depolarization and repolarization. Whether exercise alters skeletal muscle electrophysiological properties controlled by these ion channels is unclear. The present study tested the hypothesis that endurance exercise modifies diaphragm action potential properties. Exercised rats spent 8 wk with free access to running wheels, and they were compared with sedentary rats living in conventional rodent housing. Diaphragm muscle was subsequently removed under anesthesia and studied in vitro. Resting membrane potential was not affected by endurance exercise. Muscle from exercised rats had a slower rate of action potential repolarization than that of sedentary animals (P = 0.0098), whereas rate of depolarization was similar in the two groups. The K+ channel blocker 3,4-diaminopyridine slowed action potential repolarization and increased action potential area of both exercised and sedentary muscle. However, these effects were significantly smaller in diaphragm from exercised than sedentary rats. These data indicate that voluntary running slows diaphragm action potential repolarization, most likely by modulating K+ channel number or function.

  9. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    PubMed

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  10. Pharmacological actions and potential uses of Momordica charantia: a review.

    PubMed

    Grover, J K; Yadav, S P

    2004-07-01

    Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine. Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant. Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient. Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori. Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease). There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results.

  11. Epidermal Laser Stimulation of Action Potentials in the Frog Sciatic Nerve

    DTIC Science & Technology

    2008-10-01

    Laser Stimulation of Action Potentials in the Frog Sciatic Nerve Nichole M. Jindra Robert J. Thomas Human Effectiveness Directorate Directed...in the Frog Sciatic Nerve 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) .Nichole M. Jindra, Robert J. Thomas, Douglas N...Alan Rice 14. ABSTRACT Measurements of laser stimulated action potentials in the sciatic nerve of leopard frogs (Rana pipiens) were made using

  12. Uniform Action Potential Repolarization within the Sarcolemma of In Situ Ventricular Cardiomyocytes

    PubMed Central

    Bu, Guixue; Adams, Heather; Berbari, Edward J.; Rubart, Michael

    2009-01-01

    Previous studies have speculated, based on indirect evidence, that the action potential at the transverse (t)-tubules is longer than at the surface membrane in mammalian ventricular cardiomyocytes. To date, no technique has enabled recording of electrical activity selectively at the t-tubules to directly examine this hypothesis. We used confocal line-scan imaging in conjunction with the fast response voltage-sensitive dyes ANNINE-6 and ANNINE-6plus to resolve action potential-related changes in fractional dye fluorescence (ΔF/F) at the t-tubule and surface membranes of in situ mouse ventricular cardiomyocytes. Peak ΔF/F during action potential phase 0 depolarization averaged −21% for both dyes. The shape and time course of optical action potentials measured with the water-soluble ANNINE-6plus were indistinguishable from those of action potentials recorded with intracellular microelectrodes in the absence of the dye. In contrast, optical action potentials measured with the water-insoluble ANNINE-6 were significantly prolonged compared to the electrical recordings obtained from dye-free hearts, suggesting electrophysiological effects of ANNINE-6 and/or its solvents. With either dye, the kinetics of action potential-dependent changes in ΔF/F during repolarization were found to be similar at the t-tubular and surface membranes. This study provides what to our knowledge are the first direct measurements of t-tubule electrical activity in ventricular cardiomyocytes, which support the concept that action potential duration is uniform throughout the sarcolemma of individual cells. PMID:19289075

  13. Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.

    PubMed

    Jackson, M B; Konnerth, A; Augustine, G J

    1991-01-15

    Hormone release from nerve terminals in the neurohypophysis is a sensitive function of action potential frequency. We have investigated the cellular mechanisms responsible for this frequency-dependent facilitation by combining patch clamp and fluorimetric Ca2+ measurements in single neurosecretory terminals in thin slices of the rat posterior pituitary. In these terminals both action potential-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) and action potential duration were enhanced by high-frequency stimuli, all with a frequency dependence similar to that of hormone release. Furthermore, brief voltage clamp pulses inactivated a K+ current with a very similar frequency dependence. These results support a model for frequency-dependent facilitation in which the inactivation of a K+ current broadens action potentials, leading to an enhancement of [Ca2+]i signals. Further experiments tested for a causal relationship between action potential broadening and facilitation of [Ca2+]i changes. First, increasing the duration of depolarization, either by broadening action potentials with the K(+)-channel blocker tetraethylammonium or by applying longer depolarizing voltage clamp steps, increased [Ca2+]i changes. Second, eliminating frequency-dependent changes in duration, by voltage clamping the terminal with constant duration pulses, substantially reduced the frequency-dependent enhancement of [Ca2+]i changes. These results indicate that action potential broadening contributes to frequency-dependent facilitation of [Ca2+]i changes. However, the small residual frequency dependence of [Ca2+]i changes seen with constant duration stimulation suggests that a second process, distinct from action potential broadening, also contributes to facilitation. These two frequency-dependent mechanisms may also contribute to activity-dependent plasticity in synaptic terminals.

  14. Screening fluorescent voltage indicators with spontaneously spiking HEK cells.

    PubMed

    Park, Jeehae; Werley, Christopher A; Venkatachalam, Veena; Kralj, Joel M; Dib-Hajj, Sulayman D; Waxman, Stephen G; Cohen, Adam E

    2013-01-01

    Development of improved fluorescent voltage indicators is a key challenge in neuroscience, but progress has been hampered by the low throughput of patch-clamp characterization. We introduce a line of non-fluorescent HEK cells that stably express NaV 1.3 and KIR 2.1 and generate spontaneous electrical action potentials. These cells enable rapid, electrode-free screening of speed and sensitivity of voltage sensitive dyes or fluorescent proteins on a standard fluorescence microscope. We screened a small library of mutants of archaerhodopsin 3 (Arch) in spiking HEK cells and identified two mutants with greater voltage-sensitivity than found in previously published Arch voltage indicators.

  15. Solar Decameter Spikes

    NASA Astrophysics Data System (ADS)

    Melnik, V. N.; Shevchuk, N. V.; Konovalenko, A. A.; Rucker, H. O.; Dorovskyy, V. V.; Poedts, S.; Lecacheux, A.

    2014-05-01

    We analyze and discuss the properties of decameter spikes observed in July - August 2002 by the UTR-2 radio telescope. These bursts have a short duration (about one second) and occur in a narrow frequency bandwidth (50 - 70 kHz). They are chaotically located in the dynamic spectrum. Decameter spikes are weak bursts: their fluxes do not exceed 200 - 300 s.f.u. An interesting feature of these spikes is the observed linear increase of the frequency bandwidth with frequency. This dependence can be explained in the framework of the plasma mechanism that causes the radio emission, taking into account that Langmuir waves are generated by fast electrons within a narrow angle θ≈13∘ - 18∘ along the direction of the electron propagation. In the present article we consider the problem of the short lifetime of decameter spikes and discuss why electrons generate plasma waves in limited regions.

  16. A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

    PubMed

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

    2008-01-15

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

  17. Modeling of action potential generation in NG108-15 cells.

    PubMed

    Molnar, Peter; Hickman, James J

    2014-01-01

    In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.

  18. Effects of sparfloxacin, grepafloxacin, moxifloxacin, and ciprofloxacin on cardiac action potential duration.

    PubMed

    Patmore, L; Fraser, S; Mair, D; Templeton, A

    2000-10-20

    Fluoroquinolone antibiotics have been associated with QT prolongation following administration to humans. This study compares the effects of four fluoroquinolones, sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin on action potential duration recorded from canine isolated cardiac Purkinje fibres. Left and right ventricular Purkinje fibres were isolated from canine hearts and continuously superfused with physiological salt solution. Action potential duration at 90% repolarization was recorded via intracellular microelectrodes. Sparfloxacin, grepafloxacin, moxifloxacin and ciprofloxacin prolonged action potential duration in a concentration dependent manner. Mean concentrations causing a 15% prolongation of action potential duration recorded at a stimulation frequency of 1 Hz were: sparfloxacin 4.2+/-0.7 microg/ml; grepafloxacin 9.3+/-0.9 microg/ml; moxifloxacin 9.9+/-1.6 microg/ml and ciprofloxacin 72.8+/-26.4 microg/ml. Prolongation was inverse frequency dependent with larger increases in action potential duration occurring when the stimulation frequency was reduced to 0.5 Hz. These results indicate that effects on action potential duration vary within this class of compound. Rank order of potency was sparfloxacin > grepafloxacin = moxifloxacin > ciprofloxacin.

  19. A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

    PubMed Central

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G.; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N.

    2008-01-01

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (ICa,L) and Cai cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35–37°C. Incorporating a minimal seven-state Markovian model of ICa,L that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Cai cycling model, the new model replicates experimentally observed action potential duration and Cai transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing. PMID:18160660

  20. 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.

  1. Mapping Spikes to Sensations

    PubMed Central

    Stüttgen, Maik C.; Schwarz, Cornelius; Jäkel, Frank

    2011-01-01

    Single-unit recordings conducted during perceptual decision-making tasks have yielded tremendous insights into the neural coding of sensory stimuli. In such experiments, detection or discrimination behavior (the psychometric data) is observed in parallel with spike trains in sensory neurons (the neurometric data). Frequently, candidate neural codes for information read-out are pitted against each other by transforming the neurometric data in some way and asking which code’s performance most closely approximates the psychometric performance. The code that matches the psychometric performance best is retained as a viable candidate and the others are rejected. In following this strategy, psychometric data is often considered to provide an unbiased measure of perceptual sensitivity. It is rarely acknowledged that psychometric data result from a complex interplay of sensory and non-sensory processes and that neglect of these processes may result in misestimating psychophysical sensitivity. This again may lead to erroneous conclusions regarding the adequacy of candidate neural codes. In this review, we first discuss requirements on the neural data for a subsequent neurometric-psychometric comparison. We then focus on different psychophysical tasks for the assessment of detection and discrimination performance and the cognitive processes that may underlie their execution. We discuss further factors that may compromise psychometric performance and how they can be detected or avoided. We believe that these considerations point to shortcomings in our understanding of the processes underlying perceptual decisions, and therefore offer potential for future research. PMID:22084627

  2. Training Deep Spiking Neural Networks Using Backpropagation

    PubMed Central

    Lee, Jun Haeng; Delbruck, Tobi; Pfeiffer, Michael

    2016-01-01

    Deep spiking neural networks (SNNs) hold the potential for improving the latency and energy efficiency of deep neural networks through data-driven event-based computation. However, training such networks is difficult due to the non-differentiable nature of spike events. In this paper, we introduce a novel technique, which treats the membrane potentials of spiking neurons as differentiable signals, where discontinuities at spike times are considered as noise. This enables an error backpropagation mechanism for deep SNNs that follows the same principles as in conventional deep networks, but works directly on spike signals and membrane potentials. Compared with previous methods relying on indirect training and conversion, our technique has the potential to capture the statistics of spikes more precisely. We evaluate the proposed framework on artificially generated events from the original MNIST handwritten digit benchmark, and also on the N-MNIST benchmark recorded with an event-based dynamic vision sensor, in which the proposed method reduces the error rate by a factor of more than three compared to the best previous SNN, and also achieves a higher accuracy than a conventional convolutional neural network (CNN) trained and tested on the same data. We demonstrate in the context of the MNIST task that thanks to their event-driven operation, deep SNNs (both fully connected and convolutional) trained with our method achieve accuracy equivalent with conventional neural networks. In the N-MNIST example, equivalent accuracy is achieved with about five times fewer computational operations. PMID:27877107

  3. Training Deep Spiking Neural Networks Using Backpropagation.

    PubMed

    Lee, Jun Haeng; Delbruck, Tobi; Pfeiffer, Michael

    2016-01-01

    Deep spiking neural networks (SNNs) hold the potential for improving the latency and energy efficiency of deep neural networks through data-driven event-based computation. However, training such networks is difficult due to the non-differentiable nature of spike events. In this paper, we introduce a novel technique, which treats the membrane potentials of spiking neurons as differentiable signals, where discontinuities at spike times are considered as noise. This enables an error backpropagation mechanism for deep SNNs that follows the same principles as in conventional deep networks, but works directly on spike signals and membrane potentials. Compared with previous methods relying on indirect training and conversion, our technique has the potential to capture the statistics of spikes more precisely. We evaluate the proposed framework on artificially generated events from the original MNIST handwritten digit benchmark, and also on the N-MNIST benchmark recorded with an event-based dynamic vision sensor, in which the proposed method reduces the error rate by a factor of more than three compared to the best previous SNN, and also achieves a higher accuracy than a conventional convolutional neural network (CNN) trained and tested on the same data. We demonstrate in the context of the MNIST task that thanks to their event-driven operation, deep SNNs (both fully connected and convolutional) trained with our method achieve accuracy equivalent with conventional neural networks. In the N-MNIST example, equivalent accuracy is achieved with about five times fewer computational operations.

  4. Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels.

    PubMed

    Telinius, Niklas; Majgaard, Jens; Kim, Sukhan; Katballe, Niels; Pahle, Einar; Nielsen, Jørn; Hjortdal, Vibeke; Aalkjaer, Christian; Boedtkjer, Donna Briggs

    2015-07-15

    Voltage-gated sodium channels (VGSC) play a key role for initiating action potentials (AP) in excitable cells. VGSC in human lymphatic vessels have not been investigated. In the present study, we report the electrical activity and APs of small human lymphatic collecting vessels, as well as mRNA expression and function of VGSC in small and large human lymphatic vessels. The VGSC blocker TTX inhibited spontaneous contractions in six of 10 spontaneously active vessels, whereas ranolazine, which has a narrower VGSC blocking profile, had no influence on spontaneous activity. TTX did not affect noradrenaline-induced contractions. The VGSC opener veratridine induced contractions in a concentration-dependent manner (0.1-30 μm) eliciting a stable tonic contraction and membrane depolarization to -18 ± 0.6 mV. Veratridine-induced depolarizations and contractions were reversed ∼80% by TTX, and were dependent on Ca(2+) influx via L-type calcium channels and the sodium-calcium exchanger in reverse mode. Molecular analysis determined NaV 1.3 to be the predominantly expressed VGSC isoform. Electrophysiology of mesenteric lymphatics determined the resting membrane potential to be -45 ± 1.7 mV. Spontaneous APs were preceded by a slow depolarization of 5.3 ± 0.6 mV after which a spike was elicited that almost completely repolarized before immediately depolarizing again to plateau. Vessels transiently hyperpolarized prior to returning to the resting membrane potential. TTX application blocked APs. We have shown that VGSC are necessary for initiating and maintaining APs and spontaneous contractions in human lymphatic vessels and our data suggest the main contribution from comes NaV 1.3. We have also shown that activation of these channels augments the contractile activity of the vessels.

  5. 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.

  6. Direct depolarization and antidromic action potentials transiently suppress dendritic IPSPs in hippocampal CA1 pyramidal cells.

    PubMed

    Morishita, W; Alger, B E

    2001-01-01

    Whole-cell current-clamp recordings were made from distal dendrites of rat hippocampal CA1 pyramidal cells. Following depolarization of the dendritic membrane by direct injection of current pulses or by back-propagating action potentials elicited by antidromic stimulation, evoked gamma-aminobutyric acid-A (GABA(A)) receptor-mediated inhibitory postsynaptic potentials (IPSPs) were transiently suppressed. This suppression had properties similar to depolarization-induced suppression of inhibition (DSI): it was enhanced by carbachol, blocked by dendritic hyperpolarization sufficient to prevent action potential invasion, and reduced by 4-aminopyridine (4-AP) application. Thus DSI or a DSI-like process can be recorded in CA1 distal dendrites. Moreover, localized application of TTX to stratum pyramidale blocked somatic action potentials and somatic IPSPs, but not dendritic IPSPs or DSI induced by direct dendritic depolarization, suggesting DSI is expressed in part in the dendrites. These data extend the potential physiological roles of DSI.

  7. The Flash-Triggering Action Potential of the Luminescent Dinoflagellate Noctiluca

    PubMed Central

    Eckert, Roger; Sibaoka, Takao

    1968-01-01

    The action potential which elicits luminescence in Noctiluca is recorded from the flotation vacuole as a transient all-or-none hyperpolarization in response to either local or general application of inward (bath to vacuole) current. Experiments were performed to determine whether the unorthodox polarities of both the stimulus current and the potential response resulted from uncommon bioelectric mechanisms or from special morphological features of this species. The findings all indicate that the action potential belongs to the familiar class of responses which have their origin in voltage- and time-dependent selective increases in membrane permeability, and that morphological factors account for the observed deviations from normal behavior. Both the stimulus and the response have orthodox polarities provided the vacuole is designated as an "external" extracytoplasmic compartment. Differential recording between vacuole and cytoplasm showed that the action potential occurs across the vacuolar membrane, with the cytoplasmic potential, which at rest is negative with respect to the vacuole, overshooting zero and reversing sign to become transiently electropositive. The rising phase of the action potential therefore depends on active current flow through the vacuolar membrane from the vacuole into the cytoplasm. Propagation of the action potential over the subspherical cell from the locus of stimulation is thought to depend largely on the core conductor properties of the thin perivacuolar shell of cytoplasm which is bounded on its inner surface by the excitable membrane and on its outer surface by inexcitable membranes. PMID:5672004

  8. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    PubMed

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  9. Prospective Coding by Spiking Neurons

    PubMed Central

    Brea, Johanni; Gaál, Alexisz Tamás; Senn, Walter

    2016-01-01

    Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron’s firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ). PMID:27341100

  10. Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex

    PubMed Central

    Komlósi, Gergely; Füle, Miklós; Szabadics, János; Varga, Csaba; Barzó, Pál; Tamás, Gábor

    2008-01-01

    Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date. We recorded the first dataset, to our knowledge, on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action potentials in the human neocortical network. Brain slices were prepared from nonpathological samples of cortex that had to be removed for the surgical treatment of brain areas beneath association cortices of 58 patients aged 18 to 73 y. Simultaneous triple and quadruple whole-cell patch clamp recordings were performed testing mono- and polysynaptic potentials in target neurons following a single action potential fired by layer 2/3 pyramidal cells, and the temporal structure of events and underlying mechanisms were analyzed. In addition to monosynaptic postsynaptic potentials, individual action potentials in presynaptic pyramidal cells initiated long-lasting (37 ± 17 ms) sequences of events in the network lasting an order of magnitude longer than detected previously in other species. These event series were composed of specifically alternating glutamatergic and GABAergic postsynaptic potentials and required selective spike-to-spike coupling from pyramidal cells to GABAergic interneurons producing concomitant inhibitory as well as excitatory feed-forward action of GABA. Single action potentials of human neurons are sufficient to recruit Hebbian-like neuronal assemblies that are proposed to participate in cognitive processes. PMID:18767905

  11. Spectrotemporal processing differences between auditory cortical fast-spiking and regular-spiking neurons

    PubMed Central

    Atencio, Craig A.; Schreiner, Christoph E.

    2008-01-01

    Excitatory pyramidal neurons and inhibitory interneurons constitute the main elements of cortical circuitry and have distinctive morphologic and electrophysiological properties. Here, we differentiate them by analyzing the time course of their action potentials (APs) and characterizing their receptive field properties in auditory cortex. Pyramidal neurons have longer APs and discharge as Regular-Spiking Units (RSUs), while basket and chandelier cells, which are inhibitory interneurons, have shorter APs and are Fast-Spiking Units (FSUs). To compare these neuronal classes we stimulated cat primary auditory cortex neurons with a dynamic moving ripple stimulus and constructed single-unit spectrotemporal receptive fields (STRFs) and their associated nonlinearities. FSUs had shorter latencies, broader spectral tuning, greater stimulus specificity, and higher temporal precision than RSUs. The STRF structure of FSUs was more separable, suggesting more independence between spectral and temporal processing regimes. The nonlinearities associated with the two cell classes was indicative of higher feature selectivity for FSUs. These global functional differences between RSUs and FSUs suggest fundamental distinctions between putative excitatory and inhibitory neurons that shape auditory cortical processing. PMID:18400888

  12. Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium. A computer modeling study.

    PubMed

    Lesh, M D; Pring, M; Spear, J F

    1989-11-01

    Although slow conduction is a requirement for the preparation of sustained reentry, it alone is not sufficient for the initiation of reentry. Additionally, unidirectional block and recovery of excitability distal to the site of block must occur. Thus, a comprehensive description of the electrophysiological determinants of reentry must explain both slow conduction and unidirectional block. Although there is a growing body of research exploring the influence of axial resistivity and anisotropy on slow conduction, somewhat less is known about the relation of axial resistivity to spatial dispersion of action potential duration, a condition favorable to the development of unidirectional block. We hypothesized that when cells are well coupled, local differences in intrinsic action potential duration are not evident and that, as axial resistivity increases, local variation in action potential duration becomes manifest. We tested this hypothesis in a numerical model of electrical propagation in a grid of resistively coupled ionic current sources simulating a sheet of ventricular myocardium. Spatial dispersion of intrinsic action potential duration was simulated by varying the magnitude of the fully activated slow inward conductance in Beeler-Reuter membrane ionic kinetics. By then altering coupling resistance, we showed that dispersion of manifest action potential duration is masked in the setting of normal low-resistance cellular coupling and unmasked by increased axial resistance. When nonuniform anisotropy was simulated, dramatic pacing-site-dependent changes in both the pattern of activation and dispersion of action potential duration were noted. These findings may be important in understanding the mechanism of reentrant tachycardia initiation in the border zone of chronic, healed myocardial infarctions where evidence suggests that abnormal cellular coupling is the predominant electrophysiological derangement. In this study, we have shown, using a detailed ionic

  13. Active action potential propagation but not initiation in thalamic interneuron dendrites

    PubMed Central

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  14. Effect of an educational game on university students' learning about action potentials.

    PubMed

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

    2017-06-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na(+)-K(+)-ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials.

  15. Extracellular calcium transients and action potential configuration changes related to post-stimulatory potentiation in rabbit atrium.

    PubMed

    Hilgemann, D W

    1986-05-01

    Extracellular calcium transients were monitored with 2 mM tetramethylmurexide at low calcium (250 microM total, 130 microM free), and action potentials were monitored together with developed tension at normal calcium (1.3 mM) during the production and decay of post-stimulatory potentiation in rabbit left atrial strips. At normal calcium, the contractile potentiation produced by a brief burst of 4 Hz stimulation is lost in three to five post-stimulatory excitations, which correlate with a negative staircase of the late action potential. At low calcium, stimulation at 4 Hz for 3-8 s results in a net extracellular calcium depletion of 5-15 microM. At the subsequent potentiated contraction (1-45 s rest), total extracellular calcium increases by 4-8 microM. The contractile response at a second excitation is greatly suppressed and results in little or no further calcium shift; the sequence can be repeated immediately thereafter. Reducing external sodium to 60 mM (sucrose replacement) enhances post-rest contractions, suppresses the late action potential, nearly eliminates loss of contractility and net calcium efflux at post-rest excitations, and markedly reduces extracellular calcium depletion during rapid stimulation. 4-Aminopyridine (1 mM) markedly suppresses the rapid early repolarization of this preparation at post-rest excitations and the loss of contractility at post-rest stimulation from the rested state; during a post-stimulatory potentiation sequence at low calcium, replenishment of extracellular calcium takes several post-stimulatory excitations. Ryanodine (10 nM to 5 microM) abolishes the post-stimulatory contraction at rest periods of greater than 5 s. If the initial repolarization is rapid, ryanodine suppresses the late action potential, calcium efflux during quiescence is greatly accelerated, and subsequent excitations do not result in an accumulation of extracellular calcium. A positive staircase of the early action potential correlates with the magnitude

  16. Integration of asynchronously released quanta prolongs the postsynaptic spike window.

    PubMed

    Iremonger, Karl J; Bains, Jaideep S

    2007-06-20

    Classically, the release of glutamate in response to a presynaptic action potential causes a brief increase in postsynaptic excitability. Previous reports indicate that at some central synapses, a single action potential can elicit multiple, asynchronous release events. This raises the possibility that the temporal dynamics of neurotransmitter release may determine the duration of altered postsynaptic excitability. In response to physiological challenges, the magnocellular neurosecretory cells (MNCs) in the paraventricular nucleus of the hypothalamus (PVN) exhibit robust and prolonged increases in neuronal activity. Although the postsynaptic conductances that may facilitate this form of activity have been investigated thoroughly, the role of presynaptic release has been largely overlooked. Because the specific patterns of activity generated by MNCs require the activation of excitatory synaptic inputs, we sought to characterize the release dynamics at these synapses and determine whether they contribute to prolonged excitability in these cells. We obtained whole-cell recordings from MNCs in brain slices of postnatal day 21-44 rats. Stimulation of glutamatergic inputs elicited large and prolonged postsynaptic events that resulted from the summation of multiple, asynchronously released quanta. Asynchronous release was selectively inhibited by the slow calcium buffer EGTA-AM and potentiated by brief high-frequency stimulus trains. These trains caused a prolonged increase in postsynaptic spike activity that could also be eliminated by EGTA-AM. Our results demonstrate that glutamatergic terminals in PVN exhibit asynchronous release, which is important in generating large postsynaptic depolarizations and prolonged spiking in response to brief, high-frequency bursts of presynaptic activity.

  17. Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons

    PubMed Central

    Kim, Sooyun; Guzman, Segundo J; Hu, Hua; Jonas, Peter

    2013-01-01

    CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. PMID:22388958

  18. Acute Alterations of Somatodendritic Action Potential Dynamics in Hippocampal CA1 Pyramidal Cells after Kainate-Induced Status Epilepticus in Mice

    PubMed Central

    Minge, Daniel; Bähring, Robert

    2011-01-01

    Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP) dynamics immediately following status epilepticus (SE) in mice. SE was induced by intraperitoneal (i.p.) injection of kainate, and behavioral manifestation of SE was monitored for 3–4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2–5 mV). No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst) firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP), was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP)-induced Ca2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na+ and K+ current components. PMID:22039527

  19. Prevention of Ca(2+)-mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current.

    PubMed Central

    Pape, H C; Budde, T; Mager, R; Kisvárday, Z F

    1994-01-01

    1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole-cell current-clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue, with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole-cell voltage-clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage-dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na(+)-K(+)-mediated spikes: the T-type Ca2+ current (IT) and an A-type K+ current (IA). Taking into account the differences in membrane surface area, the average size of IT was similar in the two types of neurones, and interneurones possessed a slightly larger A-conductance. 4. In local circuit neurones, the ranges of steady-state inactivation and activation of IT and IA were largely overlapping (VH = 81.1 vs. -82.8 mV), both currents activated at around -70 mV, and they rapidly increased in amplitude with further depolarization. In relay cells, the inactivation curve of IT was negatively shifted along the voltage axis by about 20 mV compared with that of IA (Vh = -86.1 vs. -69.2 mV), and the activation threshold for IT (at -80 mV) was 20 mV more negative than that for IA. In interneurones, the activation range of IT was shifted to values more positive than that in relay cells (Vh = -54.9 vs. -64.5 mV), whereas the activation range of IA was more negative (Vh = -25.2 vs. -14.5 mV). 5. Under whole

  20. Single-trial imaging of spikes and synaptic potentials in single neurons in brain slices with genetically encoded hybrid voltage sensor

    PubMed Central

    Ghitani, Nima; Bayguinov, Peter O.; Ma, Yihe

    2014-01-01

    Genetically encoded voltage sensors expand the optogenetics toolkit into the important realm of electrical recording, enabling researchers to study the dynamic activity of complex neural circuits in real time. However, these probes have thus far performed poorly when tested in intact neural circuits. Hybrid voltage sensors (hVOS) enable the imaging of voltage by harnessing the resonant energy transfer that occurs between a genetically encoded component, a membrane-tethered fluorescent protein that serves as a donor, and a small charged molecule, dipicrylamine, which serves as an acceptor. hVOS generates optical signals as a result of voltage-induced changes in donor-acceptor distance. We expressed the hVOS probe in mouse brain by in utero electroporation and in transgenic mice with a neuronal promoter. Under conditions favoring sparse labeling we could visualize single-labeled neurons. hVOS imaging reported electrically evoked fluorescence changes from individual neurons in slices from entorhinal cortex, somatosensory cortex, and hippocampus. These fluorescence signals tracked action potentials in individual neurons in a single trial with excellent temporal fidelity, producing changes that exceeded background noise by as much as 16-fold. Subthreshold synaptic potentials were detected in single trials in multiple distinct cells simultaneously. We followed signal propagation between different cells within one field of view and between dendrites and somata of the same cell. hVOS imaging thus provides a tool for high-resolution recording of electrical activity from genetically targeted cells in intact neuronal circuits. PMID:25411462

  1. Pre- and postnatal differences in membrane, action potential, and ion channel properties of rostral nucleus of the solitary tract neurons

    PubMed Central

    Suwabe, Takeshi; Mistretta, Charlotte M.; Krull, Catherine

    2011-01-01

    There is little known about the prenatal development of the rostral nucleus of the solitary tract (rNST) neurons in rodents or the factors that influence circuit formation. With morphological and electrophysiological techniques in vitro, we investigated differences in the biophysical properties of rNST neurons in pre- and postnatal rats from embryonic day 14 (E14) through postnatal day 20. Developmental changes in passive membrane and action potential (AP) properties and the emergence and maturation of ion channels important in neuron function were characterized. Morphological maturation of rNST neurons parallels changes in passive membrane properties. Mean soma size, dendritic branch points, neurite endings, and neurite length all increase prenatally. whereas neuron resting membrane potential, input resistance, and time constant decrease. Dendritic spines, on the other hand, develop after birth. AP discharge patterns alter in pre- and postnatal stages. At E14, neurons generated a single TTX-sensitive, voltage-gated Na+ AP when depolarized; a higher discharge rate appeared at older stages. AP amplitude, half-width, and rise and fall times all change during development. Responses to current injection revealed a number of voltage-gated conductances in embryonic rNST, including a hyperpolarization-activated inward current and a low-threshold Ca2+ current that initiated Ca2+ spikes. A hyperpolarization-activated, transient outward potassium current was also present in the developing neurons. Although the properties of these channels change during development, they are present before synapses form and therefore, can contribute to initial establishment of neural circuits, as well as to the changing electrophysiological properties in developing rNST neurons. PMID:21865434

  2. Electrophysiological Actions of Oxytocin on the Rabbit Myometrium

    PubMed Central

    Kleinhaus, A. L.; Kao, C. Y.

    1969-01-01

    The electrical activities of myometrial cells of the pregnant rabbit uterus have been studied by means of sucrose-gap and intracellular micro-electrode recording techniques. The resting potential of the myometrial cell was about -50 mv, and it is unaffected by the duration of pregnancy or placental attachment. Action potentials of the myometrium, although dependent on external Na+, were not always of the regenerative type; preparations from nonparturient uteri often produce mainly small spikes. The mean spike amplitude was 35 mv, rising at a mean maximum rate of 3 v/sec. Oxytocin, in concentrations less than 500 µU/ml, increased the mean spike amplitude to 48 mv and the mean maximum rate of rise to 7 v/sec, without affecting the resting potential. The relation between membrane potential and dV/dt of the spike was steepened by oxytocin, suggesting that oxytocin increased the number of normally sparse sodium gates in the myometrial membrane. By this action, oxytocin is believed to increase the probability of successful regenerative spikes and thereby initiate electrical activity in quiescent preparations, increase the frequency of burst discharges, the number of spikes in each burst, and the amplitude of spikes in individual cells. PMID:5783010

  3. Cell type- and activity-dependent extracellular correlates of intracellular spiking

    PubMed Central

    Perin, Rodrigo; Buzsáki, György; Markram, Henry; Koch, Christof

    2015-01-01

    Despite decades of extracellular action potential (EAP) recordings monitoring brain activity, the biophysical origin and inherent variability of these signals remain enigmatic. We performed whole cell patch recordings of excitatory and inhibitory neurons in rat somatosensory cortex slice while positioning a silicon probe in their vicinity to concurrently record intra- and extracellular voltages for spike frequencies under 20 Hz. We characterize biophysical events and properties (intracellular spiking, extracellular resistivity, temporal jitter, etc.) related to EAP recordings at the single-neuron level in a layer-specific manner. Notably, EAP amplitude was found to decay as the inverse of distance between the soma and the recording electrode with similar (but not identical) resistivity across layers. Furthermore, we assessed a number of EAP features and their variability with spike activity: amplitude (but not temporal) features varied substantially (∼30–50% compared with mean) and nonmonotonically as a function of spike frequency and spike order. Such EAP variation only partly reflects intracellular somatic spike variability and points to the plethora of processes contributing to the EAP. Also, we show that the shape of the EAP waveform is qualitatively similar to the negative of the temporal derivative to the intracellular somatic voltage, as expected from theory. Finally, we tested to what extent EAPs can impact the lowpass-filtered part of extracellular recordings, the local field potential (LFP), typically associated with synaptic activity. We found that spiking of excitatory neurons can significantly impact the LFP at frequencies as low as 20 Hz. Our results question the common assertion that the LFP acts as proxy for synaptic activity. PMID:25995352

  4. Comparison of spike sorting and thresholding of voltage waveforms for intracortical brain-machine interface performance

    NASA Astrophysics Data System (ADS)

    Christie, Breanne P.; Tat, Derek M.; Irwin, Zachary T.; Gilja, Vikash; Nuyujukian, Paul; Foster, Justin D.; Ryu, Stephen I.; Shenoy, Krishna V.; Thompson, David E.; Chestek, Cynthia A.

    2015-02-01

    Objective. For intracortical brain-machine interfaces (BMIs), action potential voltage waveforms are often sorted to separate out individual neurons. If these neurons contain independent tuning information, this process could increase BMI performance. However, the sorting of action potentials (‘spikes’) requires high sampling rates and is computationally expensive. To explicitly define the difference between spike sorting and alternative methods, we quantified BMI decoder performance when using threshold-crossing events versus sorted action potentials. Approach. We used data sets from 58 experimental sessions from two rhesus macaques implanted with Utah arrays. Data were recorded while the animals performed a center-out reaching task with seven different angles. For spike sorting, neural signals were sorted into individual units by using a mixture of Gaussians to cluster the first four principal components of the waveforms. For thresholding events, spikes that simply crossed a set threshold were retained. We decoded the data offline using both a Naïve Bayes classifier for reaching direction and a linear regression to evaluate hand position. Main results. We found the highest performance for thresholding when placing a threshold between -3 and -4.5 × Vrms. Spike sorted data outperformed thresholded data for one animal but not the other. The mean Naïve Bayes classification accuracy for sorted data was 88.5% and changed by 5% on average when data were thresholded. The mean correlation coefficient for sorted data was 0.92, and changed by 0.015 on average when thresholded. Significance. For prosthetics applications, these results imply that when thresholding is used instead of spike sorting, only a small amount of performance may be lost. The utilization of threshold-crossing events may significantly extend the lifetime of a device because these events are often still detectable once single neurons are no longer isolated.

  5. Advances in applications of spiking neuron networks

    NASA Astrophysics Data System (ADS)

    Cios, Krzysztof J.; Sala, Dorel M.

    2000-03-01

    In this paper, we present new findings in constructing and applications of artificial neural networks that use a biologically inspired spiking neuron model. The used model is a point neuron with the interaction between neurons described by postsynaptic potentials. The synaptic plasticity is achieved by using a temporal correlation learning rule, specified as a function of time difference between the firings of pre- and post-synaptic neurons. Using this rule we show how certain associations between neurons in a network of spiking neurons can be implemented. As an example we analyze the dynamic properties of networks of laterally connected spiking neurons and we show their capability to self-organize into topological maps in response to external stimulation. In another application we explore the capability networks of spiking neurons to solve graph algorithms by using temporal coding of distances in a given spatial configuration. The paper underlines the importance of temporal dimension in artificial neural network information processing.

  6. Natural Firing Patterns Imply Low Sensitivity of Synaptic Plasticity to Spike Timing Compared with Firing Rate

    PubMed Central

    Wallisch, Pascal; Ostojic, Srdjan

    2016-01-01

    Synaptic plasticity is sensitive to the rate and the timing of presynaptic and postsynaptic action potentials. In experimental protocols inducing plasticity, the imposed spike trains are typically regular and the relative timing between every presynaptic and postsynaptic spike is fixed. This is at odds with firing patterns observed in the cortex of intact animals, where cells fire irregularly and the timing between presynaptic and postsynaptic spikes varies. To investigate synaptic changes elicited by in vivo-like firing, we used numerical simulations and mathematical analysis of synaptic plasticity models. We found that the influence of spike timing on plasticity is weaker than expected from regular stimulation protocols. Moreover, when neurons fire irregularly, synaptic changes induced by precise spike timing can be equivalently induced by a modest firing rate variation. Our findings bridge the gap between existing results on synaptic plasticity and plasticity occurring in vivo, and challenge the dominant role of spike timing in plasticity. SIGNIFICANCE STATEMENT Synaptic plasticity, the change in efficacy of connections between neurons, is thought to underlie learning and memory. The dominant paradigm posits that the precise timing of neural action potentials (APs) is central for plasticity induction. This concept is based on experiments using highly regular and stereotyped patterns of APs, in stark contrast with natural neuronal activity. Using synaptic plasticity models, we investigated how irregular, in vivo-like activity shapes synaptic plasticity. We found that synaptic changes induced by precise timing of APs are much weaker than suggested by regular stimulation protocols, and can be equivalently induced by modest variations of the AP rate alone. Our results call into question the dominant role of precise AP timing for plasticity in natural conditions. PMID:27807166

  7. An application of reversible-jump Markov chain Monte Carlo to spike classification of multi-unit extracellular recordings.

    PubMed

    Nguyen, David P; Frank, Loren M; Brown, Emery N

    2003-02-01

    Multi-electrode recordings in neural tissue contain the action potential waveforms of many closely spaced neurons. While we can observe the action potential waveforms, we cannot observe which neuron is the source for which waveform nor how many source neurons are being recorded. Current spike-sorting algorithms solve this problem by assuming a fixed number of source neurons and assigning the action potentials given this fixed number. We model the spike waveforms as an anisotropic Gaussian mixture model and present, as an alternative, a reversible-jump Markov chain Monte Carlo (MCMC) algorithm to simultaneously estimate the number of source neurons and to assign each action potential to a source. We derive this MCMC algorithm and illustrate its application using simulated three-dimensional data and real four-dimensional feature vectors extracted from tetrode recordings of rat entorhinal cortex neurons. In the analysis of the simulated data our algorithm finds the correct number of mixture components (sources) and classifies the action potential waveforms with minimal error. In the analysis of real data, our algorithm identifies clusters closely resembling those previously identified by a user-dependent graphical clustering procedure. Our findings suggest that a reversible-jump MCMC algorithm could offer a new strategy for designing automated spike-sorting algorithms.

  8. Spike integration and cellular memory in a rhythmic network from Na+/K+ pump current dynamics

    PubMed Central

    Pulver, Stefan R.

    2009-01-01

    The output of a neural circuit results from an interaction between the intrinsic properties of neurons within the circuit and the features of the synaptic connections between them. The plasticity of intrinsic properties has been primarily attributed to modification of ion channel function and/or number. In this study, we demonstrate a mechanism for intrinsic plasticity in rhythmically active Drosophila neurons that is not conductance-based. Larval motor neurons show a long lasting sodium-dependent afterhyperpolarization (AHP) following bursts of action potentials that is mediated by the electrogenic activity of Na+/K+ ATPase. This AHP persists for multiple seconds following volleys of action potentials and is able to function as a pattern-insensitive integrator of spike number that is independent of external calcium. This current also interacts with endogenous Shal K+ conductances to modulate spike timing for multiple seconds following rhythmic activity, providing a cellular memory of network activity on a behaviorally relevant time scale. PMID:19966842

  9. Photodynamic action of chlorin e6 on thymocyte plasmatic and mitochondrial membrane potentials

    NASA Astrophysics Data System (ADS)

    Gyulkhandanyan, Grigor V.

    2005-08-01

    Transmembrane potentials appear to be cell state sensitive characteristics and can give information about cell damage initial stage. Photodynamic action of the photosensitizer chlorin e6 on plasmatic and mitochondrial membrane potentials of the rat thymus lymphocytes was studied using voltage-sensitive dye rhodamine 6G. It has been revealed that mitochondrial membrane potential is more sensitive characteristic of membrane disfunction than plasmatic one at the cell photodamage.

  10. Ca2+-activated K+ currents regulate odor adaptation by modulating spike encoding of olfactory receptor cells.

    PubMed Central

    Kawai, Fusao

    2002-01-01

    The olfactory system is thought to accomplish odor adaptation through the ciliary transduction machinery in olfactory receptor cells (ORCs). However, ORCs that have lost their cilia can exhibit spike frequency accommodation in which the action potential frequency decreases with time despite a steady depolarizing stimulus. This raises the possibility that somatic ionic channels in ORCs might serve for odor adaptation at the level of spike encoding, because spiking responses in ORCs encode the odor information. Here I investigate the adaptational mechanism at the somatic membrane using conventional and dynamic patch-clamp recording techniques, which enable the ciliary mechanism to be bypassed. A conditioning stimulus with an odorant-induced current markedly shifted the response range of action potentials induced by the same test stimulus to higher concentrations of the odorant, indicating odor adaptation. This effect was inhibited by charybdotoxin and iberiotoxin, Ca2+-activated K+ channel blockers, suggesting that somatic Ca2+-activated K+ currents regulate odor adaptation by modulating spike encoding. I conclude that not only the ciliary machinery but also the somatic membrane currents are crucial to odor adaptation. PMID:11916858

  11. Input-output mapping reconstruction of spike trains at dorsal horn evoked by manual acupuncture

    NASA Astrophysics Data System (ADS)

    Wei, Xile; Shi, Dingtian; Yu, Haitao; Deng, Bin; Lu, Meili; Han, Chunxiao; Wang, Jiang

    2016-12-01

    In this study, a generalized linear model (GLM) is used to reconstruct mapping from acupuncture stimulation to spike trains driven by action potential data. The electrical signals are recorded in spinal dorsal horn after manual acupuncture (MA) manipulations with different frequencies being taken at the “Zusanli” point of experiment rats. Maximum-likelihood method is adopted to estimate the parameters of GLM and the quantified value of assumed model input. Through validating the accuracy of firings generated from the established GLM, it is found that the input-output mapping of spike trains evoked by acupuncture can be successfully reconstructed for different frequencies. Furthermore, via comparing the performance of several GLMs based on distinct inputs, it suggests that input with the form of half-sine with noise can well describe the generator potential induced by acupuncture mechanical action. Particularly, the comparison of reproducing the experiment spikes for five selected inputs is in accordance with the phenomenon found in Hudgkin-Huxley (H-H) model simulation, which indicates the mapping from half-sine with noise input to experiment spikes meets the real encoding scheme to some extent. These studies provide us a new insight into coding processes and information transfer of acupuncture.

  12. Optical magnetic detection of single-neuron action potentials using NV-diamond

    NASA Astrophysics Data System (ADS)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  13. Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields.

    PubMed

    Shneider, M N; Pekker, M

    2014-05-01

    In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed.

  14. DBI potential, DBI inflation action and general Lagrangian relative to phantom, K-essence and quintessence

    SciTech Connect

    Zhang, Qing; Huang, Yong-Chang

    2011-11-01

    We derive a Dirac-Born-Infeld (DBI) potential and DBI inflation action by rescaling the metric. The determinant of the induced metric naturally includes the kinetic energy and the potential energy. In particular, the potential energy and kinetic energy can convert into each other in any order, which is in agreement with the limit of classical physics. This is quite different from the usual DBI action. We show that the Taylor expansion of the DBI action can be reduced into the form in the non-linear classical physics. These investigations are the support for the statement that the results of string theory are consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model.

  15. Optical coherence tomography for detection of compound action potential in Xenopus Laevis sciatic nerve

    NASA Astrophysics Data System (ADS)

    Troiani, Francesca; Nikolic, Konstantin; Constandinou, Timothy G.

    2016-03-01

    Due to optical coherence tomography (OCT) high spatial and temporal resolution, this technique could be used to observe the quick changes in the refractive index that accompany action potential. In this study we explore the use of time domain Optical Coherence Tomography (TD-OCT) for real time action potential detection in ex vivo Xenopus Laevis sciatic nerve. TD-OCT is the easiest and less expensive OCT technique and, if successful in detecting real time action potential, it could be used for low cost monitoring devices. A theoretical investigation into the order of magnitude of the signals detected by a TD-OCT setup is provided by this work. A linear dependence between the refractive index and the intensity changes is observed and the minimum SNR for which the setup could work is found to be SNR = 2 x 104.

  16. Initiation and blocking of the action potential in an axon in weak ultrasonic or microwave fields

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2014-05-01

    In this paper, we analyze the effect of the redistribution of the transmembrane ion channels in an axon caused by longitudinal acoustic vibrations of the membrane. These oscillations can be excited by an external source of ultrasound and weak microwave radiation interacting with the charges sitting on the surface of the lipid membrane. It is shown, using the Hodgkin-Huxley model of the axon, that the density redistribution of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At the significant redistribution of sodium channels in the membrane, the rarefaction zones of the transmembrane channel density are formed, blocking the propagation of the action potential. Blocking the action potential propagation along the axon is shown to cause anesthesia in the example case of a squid axon. Various approaches to experimental observation of the effects considered in this paper are discussed.

  17. Changes in action potential duration alter reliance of excitatory synaptic transmission on multiple types of Ca2+ channels in rat hippocampus.

    PubMed

    Wheeler, D B; Randall, A; Tsien, R W

    1996-04-01

    It has been established that multiple types of Ca2+ channels participate in triggering neurotransmitter release at central synapses, but there is uncertainty about the nature of their combined actions. We investigated synaptic transmission at CA3-CA1 synapses of rat hippocampal slices and asked whether the dependence on omega-CTx-GVIA-sensitive N-type channels and omega-Aga-IVA-sensitive P/Q-type Ca2+ channels can be altered by physiological mechanisms. The reliance on multiple types of Ca2+ channels was not absolute but depended strongly on the amount of Ca2+ influx through individual channels, which was manipulated by prolonging the presynaptic action potential with the K+ channel blocker 4-aminopyridine (4-AP) and by varying the extracellular Ca2+ concentration ([Ca2+]o). We quantified the influence of spike broadening on Ca2+ influx through various Ca2+ channels by imposing mock action potentials on voltage-clamped cerebellar granule neurons. In field recordings of the EPSP in hippocampal slices, action potential prolongation increased the EPSP slope by 2-fold and decreased its reliance on either N-type or P/Q-type Ca2+ channels. The inhibition of synaptic transmission by N-type channel blockade was virtually eliminated in the presence of 4-AP, but it could be restored by lowering [Ca2+]o. These results rule out a scenario in which a significant fraction of presynaptic terminals rely solely on N-type channels to trigger transmission. The change in sensitivity to the neurotoxins with 4-AP could be explained in terms of a nonlinear relationship between Ca2+ entry and synaptic strength, which rises steeply at low [Ca2+]o, but approaches saturation at high [Ca2+]o. This relationship was evaluated experimentally by varying [CA2+]o in the absence and presence of 4-AP. One consequence of this relationship is that down-modulation of presynaptic Ca2+ channels by various modulators would increase the relative impact of spike broadening greatly.

  18. A phantom axon setup for validating models of action potential recordings.

    PubMed

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

  19. Incorporated Fish Oil Fatty Acids Prevent Action Potential Shortening Induced by Circulating Fish Oil Fatty Acids

    PubMed Central

    Ruijter, Hester M. Den; Verkerk, Arie O.; Coronel, Ruben

    2010-01-01

    Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids (ω3-PUFAs) reduces the severity and number of arrhythmias. Long-term ω3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating ω3-PUFAs in the bloodstream and incorporated ω3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating ω3-PUFAs in the bloodstream enhance or diminish the effects of incorporated ω3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (ω3) or sunflower oil (ω9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered ω3-PUFAs. Plasma of ω3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of ω3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, ω3 myocytes had a shorter action potential with a more negative plateau than ω9 myocytes. In the ω9 myocytes, but not in the ω3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated ω3-PUFAs into the sarcolemma and acutely administered ω3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac ω3-PUFA status will probably not benefit from short term ω3 supplementation as an antiarrhythmic therapy. PMID:21423389

  20. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

    PubMed

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

    High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

  1. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

    PubMed

    Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2013-06-15

    Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations.

  2. The neuroendocrine action potential. Winner of the 2008 Frank Beach Award in Behavioral Neuroendocrinology.

    PubMed

    Hofmann, Hans A

    2010-09-01

    Animals are remarkably well equipped to respond to changes in their environment across different time scales and levels of biological organization. Here, I introduce a novel perspective that incorporates the three main processes the nervous system uses to integrate and process information: electrophysiological, genomic, and neuroendocrine action potentials. After discussing several examples of neuroendocrine action potentials, I lay out the commonalities of these temporally organized responses and how they might be interrelated with electrophysiological activity and genomic responses. This framework provides a novel outlook on longstanding questions in behavioral neuroendocrinology and suggests exciting new avenues for further research that will integrate across disciplines and levels of biological organization.

  3. Effects of some heavy metals on the action potentials of an identified Helix pomatia photosensitive neuron.

    PubMed

    Kartelija, Gordana; Radenović, Lidija; Todorović, Natasa; Nedeljković, Miodrag

    2005-06-01

    In the photosensitive MB neuron in the left parietal ganglion of Helix pomatia, the onset of light prolongs significantly (by about 40%) the duration of the action potential. The broadening of the action potential after the onset of light was found to be due to its calcium component and could not be induced after blocking Ca(2+) channels by Cd(2+) and Pb(2+) and in absence of Ca(2+) in medium. The blocking effect of both compounds was reversible. It was found that CdCl(2) exhibited a more intense blocking effect than PbCl(2).

  4. Spikes and matter inhomogeneities in massless scalar field models

    NASA Astrophysics Data System (ADS)

    Coley, A. A.; Lim, W. C.

    2016-01-01

    We shall discuss the general relativistic generation of spikes in a massless scalar field or stiff perfect fluid model. We first investigate orthogonally transitive (OT) G 2 stiff fluid spike models both heuristically and numerically, and give a new exact OT G 2 stiff fluid spike solution. We then present a new two-parameter family of non-OT G 2 stiff fluid spike solutions, obtained by the generalization of non-OT G 2 vacuum spike solutions to the stiff fluid case by applying Geroch's transformation on a Jacobs seed. The dynamics of these new stiff fluid spike solutions is qualitatively different from that of the vacuum spike solutions in that the matter (stiff fluid) feels the spike directly and the stiff fluid spike solution can end up with a permanent spike. We then derive the evolution equations of non-OT G 2 stiff fluid models, including a second perfect fluid, in full generality, and briefly discuss some of their qualitative properties and their potential numerical analysis. Finally, we discuss how a fluid, and especially a stiff fluid or massless scalar field, affects the physics of the generation of spikes.

  5. From spiking neuron models to linear-nonlinear models.

    PubMed

    Ostojic, Srdjan; Brunel, Nicolas

    2011-01-20

    Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates.

  6. 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

  7. Alternative splicing regulates kv3.1 polarized targeting to adjust maximal spiking frequency.

    PubMed

    Gu, Yuanzheng; Barry, Joshua; McDougel, Robert; Terman, David; Gu, Chen

    2012-01-13

    Synaptic inputs received at dendrites are converted into digital outputs encoded by action potentials generated at the axon initial segment in most neurons. Here, we report that alternative splicing regulates polarized targeting of Kv3.1 voltage-gated potassium (Kv) channels to adjust the input-output relationship. The spiking frequency of cultured hippocampal neurons correlated with the level of endogenous Kv3 channels. Expression of axonal Kv3.1b, the longer form of Kv3.1 splice variants, effectively converted slow-spiking young neurons to fast-spiking ones; this was not the case for Kv1.2 or Kv4.2 channel constructs. Despite having identical biophysical properties as Kv3.1b, dendritic Kv3.1a was significantly less effective at increasing the maximal firing frequency. This suggests a possible role of channel targeting in regulating spiking frequency. Mutagenesis studies suggest the electrostatic repulsion between the Kv3.1b N/C termini, created by its C-terminal splice domain, unmasks the Kv3.1b axonal targeting motif. Kv3.1b axonal targeting increased the maximal spiking frequency in response to prolonged depolarization. This finding was further supported by the results of local application of channel blockers and computer simulations. Taken together, our studies have demonstrated that alternative splicing controls neuronal firing rates by regulating the polarized targeting of Kv3.1 channels.

  8. Event-related potentials to intact and disrupted actions in children and adults

    PubMed Central

    Pace, Amy; Carver, Leslie J.; Friend, Margaret

    2013-01-01

    The current research used event-related potentials (ERPs) to investigate neurophysiological responses to intact and disrupted actions embedded within an event in children and adults. Responses were recorded as children (24-month-olds) and adults observed a relatively novel event composed of three actions. In one condition pauses were inserted at intact boundaries (i.e., at the endpoint of each action), whereas in the other condition they were inserted at breakpoints that disrupted the action (i.e., in the middle of each action). Evoked responses revealed differences across conditions in both groups; disrupted actions elicited a prolonged negative slow wave from 100 to 700 ms in children, whereas adults demonstrated two distinct negative peaks between 50–150 and 250–350 ms. These findings contribute the first electrophysiological evidence that children readily detect disruptions to ongoing events by the end of the second year, even with limited exposure to the event itself. Furthermore, they suggest that adults rely on two distinct mechanisms when processing novel events. Results are discussed in relation to the role of perceptual and conceptual levels of analysis in the development of action processing. PMID:23374603

  9. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    PubMed

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

  10. Action potential propagation and propagation block by GABA in rat posterior pituitary nerve terminals.

    PubMed Central

    Jackson, M B; Zhang, S J

    1995-01-01

    1. A theoretical model was developed to investigate action potential propagation in posterior pituitary nerve terminals. This model was then used to evaluate the efficacy of depolarizing and shunting GABA responses on action potential propagation. 2. Experimental data obtained from the posterior pituitary with patch clamp techniques were used to derive empirical expressions for the voltage and time dependence of the nerve terminal Na+ and K+ channels. The essential structure employed here was based on anatomical and cable data from the posterior pituitary, and consisted of a long cylindrical axon (diameter, 0.5 mm) with a large spherical swelling (diameter, 4-21 mm) in the middle. 3. In the absence of an inhibitory conductance, simulated action potentials propagated with high fidelity through the nerve terminal. Swellings could block propagation, but only when sizes exceeded those observed in the posterior pituitary. Adding axonal branches reduced the critical size only slightly. These results suggested that action potentials invade the entire posterior pituitary nerve terminal in the absence of inhibition or depression. 4. The addition of inhibitory conductance to a swelling caused simulated action potentials to fail at the swelling. Depolarizing inhibitory conductances were 1.6 times more effective than shunting inhibitory conductances in blocking propagation. 5. Inhibitory conductances within the range of experimentally observed magnitudes and localized to swellings in the observed range of sizes were too weak to block simulated action potentials. However, twofold enhancement of GABA responses by neurosteroid resulted in currents strong enough to block propagation in realistic swelling sizes. 6. GABA could block simulated propagation without neurosteroid enhancement provided that GABA was present throughout a region in the order of a few hundred micrometres. For this widespread inhibition depolarizing conductance was 2.2 times more effective than shunting

  11. Macroscopic Description for Networks of Spiking Neurons

    NASA Astrophysics Data System (ADS)

    Montbrió, Ernest; Pazó, Diego; Roxin, Alex

    2015-04-01

    A major goal of neuroscience, statistical physics, and nonlinear dynamics is to understand how brain function arises from the collective dynamics of networks of spiking neurons. This challenge has been chiefly addressed through large-scale numerical simulations. Alternatively, researchers have formulated mean-field theories to gain insight into macroscopic states of large neuronal networks in terms of the collective firing activity of the neurons, or the firing rate. However, these theories have not succeeded in establishing an exact correspondence between the firing rate of the network and the underlying microscopic state of the spiking neurons. This has largely constrained the range of applicability of such macroscopic descriptions, particularly when trying to describe neuronal synchronization. Here, we provide the derivation of a set of exact macroscopic equations for a network of spiking neurons. Our results reveal that the spike generation mechanism of individual neurons introduces an effective coupling between two biophysically relevant macroscopic quantities, the firing rate and the mean membrane potential, which together govern the evolution of the neuronal network. The resulting equations exactly describe all possible macroscopic dynamical states of the network, including states of synchronous spiking activity. Finally, we show that the firing-rate description is related, via a conformal map, to a low-dimensional description in terms of the Kuramoto order parameter, called Ott-Antonsen theory. We anticipate that our results will be an important tool in investigating how large networks of spiking neurons self-organize in time to process and encode information in the brain.

  12. Automated stationary source dynamic spiking. Final report

    SciTech Connect

    McGaughey, J.F.

    1998-06-17

    Methods of collection and analysis for monitoring stationary sources must demonstrate conclusively that the methodology is functioning properly and according to specified EPA criteria. The appropriate procedure for demonstrating proper operation of the method is to perform dynamic spiking of the analyte in the field, at the specified source being monitored. Gaseous dynamic spiking, using certified gas mixtures as the spiking medium has been used in previous EPA stationary source sampling methods and documented in EPA reports. Liquid dynamic spiking, using mixtures of liquid and solid analytes in an organic or aqueous solvent has also been used in previous EPA field tests. To remove, as much as possible, the potential for human error, the EPA has developed a prototype liquid dynamic spiking system employing computerized operation of the analyte spiking procedure with video monitoring and control of the liquid droplet frequency and size. This report describes development of the system applicability to stationary source sampling, the individual parts incorporated into the system, and the standard operating procedures.

  13. BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in Myelinated Axons of Cerebellar Purkinje Cells

    PubMed Central

    Hirono, Moritoshi; Ogawa, Yasuhiro; Misono, Kaori; Zollinger, Daniel R.; Trimmer, James S.

    2015-01-01

    In myelinated axons, K+ channels are clustered in distinct membrane domains to regulate action potentials (APs). At nodes of Ranvier, Kv7 channels are expressed with Na+ channels, whereas Kv1 channels flank nodes at juxtaparanodes. Regulation of axonal APs by K+ channels would be particularly important in fast-spiking projection neurons such as cerebellar Purkinje cells. Here, we show that BK/Slo1 channels are clustered at the paranodal junctions of myelinated Purkinje cell axons of rat and mouse. The paranodal junction is formed by a set of cell-adhesion molecules, including Caspr, between the node and juxtaparanodes in which it separates nodal from internodal membrane domains. Remarkably, only Purkinje cell axons have detectable paranodal BK channels, whose clustering requires the formation of the paranodal junction via Caspr. Thus, BK channels occupy this unique domain in Purkinje cell axons along with the other K+ channel complexes at nodes and juxtaparanodes. To investigate the physiological role of novel paranodal BK channels, we examined the effect of BK channel blockers on antidromic AP conduction. We found that local application of blockers to the axon resulted in a significant increase in antidromic AP failure at frequencies above 100 Hz. We also found that Ni2+ elicited a similar effect on APs, indicating the involvement of Ni2+-sensitive Ca2+ channels. Furthermore, axonal application of BK channel blockers decreased the inhibitory synaptic response in the deep cerebellar nuclei. Thus, paranodal BK channels uniquely support high-fidelity firing of APs in myelinated Purkinje cell axons, thereby underpinning the output of the cerebellar cortex. PMID:25948259

  14. Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons.

    PubMed

    Lien, Cheng-Chang; Jonas, Peter

    2003-03-15

    Kv3 channels are thought to be essential for the fast-spiking (FS) phenotype in GABAergic interneurons, but how these channels confer the ability to generate action potentials (APs) at high frequency is unknown. To address this question, we developed a fast dynamic-clamp system (approximately 50 kHz) that allowed us to add a Kv3 model conductance to CA1 oriens alveus (OA) interneurons in hippocampal slices. Selective pharmacological block of Kv3 channels by 0.3 mm 4-aminopyridine or 1 mm tetraethylammonium ions led to a marked broadening of APs during trains of short stimuli and a reduction in AP frequency during 1 sec stimuli. The addition of artificial Kv3 conductance restored the original AP pattern. Subtraction of Kv3 conductance by dynamic clamp mimicked the effects of the blockers. Application of artificial Kv3 conductance also led to FS in OA interneurons after complete K+ channel block and even induced FS in hippocampal pyramidal neurons in the absence of blockers. Adding artificial Kv3 conductance with altered deactivation kinetics revealed a nonmonotonic relationship between mean AP frequency and deactivation rate, with a maximum slightly above the original value. Insertion of artificial Kv3 conductance with either lowered activation threshold or inactivation also led to a reduction in the mean AP frequency. However, the mechanisms were distinct. Shifting the activation threshold induced adaptation, whereas adding inactivation caused frequency-dependent AP broadening. In conclusion, Kv3 channels are necessary for the FS phenotype of OA interneurons, and several of their gating properties appear to be optimized for high-frequency repetitive activity.

  15. Contribution of LFP dynamics to single-neuron spiking variability in motor cortex during movement execution

    PubMed Central

    Rule, Michael E.; Vargas-Irwin, Carlos; Donoghue, John P.; Truccolo, Wilson

    2015-01-01

    Understanding the sources of variability in single-neuron spiking responses is an important open problem for the theory of neural coding. This variability is thought to result primarily from spontaneous collective dynamics in neuronal networks. Here, we investigate how well collective dynamics reflected in motor cortex local field potentials (LFPs) can account for spiking variability during motor behavior. Neural activity was recorded via microelectrode arrays implanted in ventral and dorsal premotor and primary motor cortices of non-human primates performing naturalistic 3-D reaching and grasping actions. Point process models were used to quantify how well LFP features accounted for spiking variability not explained by the measured 3-D reach and grasp kinematics. LFP features included the instantaneous magnitude, phase and analytic-signal components of narrow band-pass filtered (δ,θ,α,β) LFPs, and analytic signal and amplitude envelope features in higher-frequency bands. Multiband LFP features predicted single-neuron spiking (1ms resolution) with substantial accuracy as assessed via ROC analysis. Notably, however, models including both LFP and kinematics features displayed marginal improvement over kinematics-only models. Furthermore, the small predictive information added by LFP features to kinematic models was redundant to information available in fast-timescale (<100 ms) spiking history. Overall, information in multiband LFP features, although predictive of single-neuron spiking during movement execution, was redundant to information available in movement parameters and spiking history. Our findings suggest that, during movement execution, collective dynamics reflected in motor cortex LFPs primarily relate to sensorimotor processes directly controlling movement output, adding little explanatory power to variability not accounted by movement parameters. PMID:26157365

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

    SciTech Connect

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi

    2013-04-26

    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 compound 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.

  17. [Double action potentials in the command neurons of Helix pomatia in response to the action of cobalt ions].

    PubMed

    Palikhova, T A; Khludova, L K; Sokolov, E N

    1987-01-01

    Cobalt chloride (20 mmol/l) in physiological solution results in generation of doublets of spikes in Helix pomatia command neurons in response to intracellularly injected depolarizing current. The extraspikes arise in arborizations of neuron and are determined by influx sodium ions. It is supposed that facilitation of extraspikes in apparently due to long-lasting blockade of calcium-dependent potassium current by Co2+ ions.

  18. Dopamine Modulation of Ih Improves Temporal Fidelity of Spike Propagation in an Unmyelinated Axon

    PubMed Central

    Ballo, Aleksander W.; Nadim, Farzan; Bucher, Dirk

    2012-01-01

    We studied how conduction delays of action potentials in an unmyelinated axon depended on the history of activity, and how this dependence was changed by the neuromodulator dopamine (DA). The pyloric dilator axons of the stomatogastric nervous system in the lobster, Homarus americanus, exhibited substantial activity-dependent hyperpolarization and changes in spike shape during repetitive activation. The conduction delays varied by several milliseconds per centimeter, and during activation with realistic burst patterns or Poisson-like patterns, changes in delay occurred over multiple time scales. The mean delay increased while the resting membrane potential hyperpolarized with a time constant of several minutes. Concomitantly with the mean delay, the variability of delay also increased. The variability of delay was not a linear or monotonic function of instantaneous spike frequency or spike shape parameters, and the relationship between these parameters changed with the increase in mean delay. Hyperpolarization was counteracted by a hyperpolarization-activated inward current (Ih), and the magnitude of Ih critically determined the temporal fidelity of spike propagation. Pharmacological block of Ih increased the change in delay and the variability of delay, and increasing Ih by application of DA diminished both. Consequently, the temporal fidelity of pattern propagation was largely improved in DA. Standard measurements of changes in excitability or delay with paired stimuli or tonic stimulation failed to capture the dynamics of spike conduction. These results indicate that spike conduction can be extremely sensitive to the history of axonal activity and to the presence of neuromodulators, with potentially important consequences for temporal coding. PMID:22496556

  19. Zinc-dependent action potentials in giant neurons of the snail, Euhadra quaestia.

    PubMed

    Kawa, K

    1979-09-14

    In giant neurons of subesophageal ganglion of the Japanese land snail, Euhadra quaestia Deshayes, permeation of Zn ions through Ca channels were investigated with a conventional current clamp method. All-or-none action potentials of long duration (90 to 120 sec) were evoked in 24 mM Zn containing salines. The overshoots were about +10 mV and the maximum rate of rises (MRRs) was about 2.9 V/sec. The amplitudes and the MRRs of the action potentials depended on external Zn ion concentrations. The action potentials were suppressed by specific Ca-channel inhibitors such as Co2+, La3+ and Verapamil, but they were resistant to Na-channel inhibitor, tetrodotoxin, even at 30 microM. It is concluded that these action potentials are generated by Zn ions permeating Ca channels in snail neuronal membrane. On the basis of Hagiwara and Takahashi's (S. Hagiwara & K. Takahashi, 1967, J. Gen. Physiol. 50:583) model of Ca channels, it is inferred that Zn ions are 5 to 10 times stronger in affinity to Ca channels than Ca ions, but 10 to 20 times less permeable.

  20. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

    ERIC Educational Resources Information Center

    Bertrand, Melanie

    2016-01-01

    In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

  1. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

    ERIC Educational Resources Information Center

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  2. Viewing Objects and Planning Actions: On the Potentiation of Grasping Behaviours by Visual Objects

    ERIC Educational Resources Information Center

    Makris, Stergios; Hadar, Aviad A.; Yarrow, Kielan

    2011-01-01

    How do humans interact with tools? Gibson (1979) suggested that humans perceive directly what tools afford in terms of meaningful actions. This "affordances" hypothesis implies that visual objects can potentiate motor responses even in the absence of an intention to act. Here we explore the temporal evolution of motor plans afforded by common…

  3. Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons.

    PubMed

    Erisir, A; Lau, D; Rudy, B; Leonard, C S

    1999-11-01

    Fast-spiking GABAergic interneurons of the neocortex and hippocampus fire high-frequency trains of brief action potentials with little spike-frequency adaptation. How these striking properties arise is unclear, although recent evidence suggests K(+) channels containing Kv3.1-Kv3.2 proteins play an important role. We investigated the role of these channels in the firing properties of fast-spiking neocortical interneurons from mouse somatosensory cortex using a pharmacological and modeling approach. Low tetraethylammonium (TEA) concentrations (action potential repolarization and high-frequency firing. Analysis of the spike trains evoked by steady depolarization revealed that, although TEA had little effect on the initial firing rate, it strongly reduced firing frequency later in the trains. These effects appeared to be specific to Kv3.1 and Kv3.2 channels, because blockade of dendrotoxin-sensitive Kv1 channels and BK Ca(2+)-activated K(+) channels, which also have high TEA sensitivity, produced opposite or no effects. Voltage-clamp experiments confirmed the presence of a Kv3.1-Kv3.2-like current in fast-spiking neurons, but not in other interneurons. Analysis of spike shape changes during the spike trains suggested that Na(+) channel inactivation plays a significant role in the firing-rate slowdown produced by TEA, a conclusion that was supported by computer simulations. These findings indicate that the unique properties of Kv3.1-Kv3.2 channels enable sustained high-frequency firing by facilitating the recovery of Na(+) channel inactivation and by minimizing the duration of the afterhyperpolarization in neocortical interneurons.

  4. Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of streptozotocin-induced diabetic rats.

    PubMed

    Kamal, A; Artola, A; Biessels, G J; Gispen, W H; Ramakers, G M J

    2003-01-01

    Diabetes mellitus is associated with impairments of cognitive function both in humans and animal models. In diabetic rats cognitive deficits are related to alterations in activity-dependent synaptic plasticity in the hippocampus. Many similarities with the pathophysiology of normal brain aging have been noted, and the view emerges that the effects of diabetes on the brain are best described as "accelerated brain aging."In the present study we examined whether CA1 pyramidal neurons from streptozotocin-induced diabetic rats display an increased slow afterhyperpolarization, often considered as a hallmark of neuronal aging. We found no differences in resting membrane potential, input resistance, membrane time-constant, and action potential amplitude and duration between CA1 pyramidal neurons from streptozotocin-induced diabetic and age-matched control rats. During a train of action potentials, however, there is an increased broadening of the action potentials in diabetic animals, so-called "spike broadening." The amplitude of the slow afterhyperpolarization elicited by a train of action potentials is indeed increased in diabetic animals. Interestingly, when the slow afterhyperpolarization is elicited by a Ca(2+) spike, there is no difference between control and diabetic rats. This indicates that the increased slow afterhyperpolarization in diabetes is likely to be due to an increased Ca(2+) influx resulting from the increased spike broadening. These data underscore the notion that the diabetic brain at the neuronal level shares properties with brain aging.

  5. Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron.

    PubMed

    Lin, Pei-Lin; Tsai, Ming-Cheng; Lu, Guan-Ling; Lu, Dah-Yuu; Chuang, Chieh-Min; Yang, Han-Yin; Huang, Shiang-Suo; Chen, Yi-Hung

    2010-01-01

    This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol

  6. Dependence of transient and residual calcium dynamics on action-potential patterning during neuropeptide secretion.

    PubMed

    Muschol, M; Salzberg, B M

    2000-09-15

    Secretion of the neuropeptide arginine vasopressin (AVP) from the neurohypophysis is optimized by short phasic bursts of action potentials with a mean intraburst frequency around 10 Hz. Several hypotheses, most prominently action-potential broadening and buildup of residual calcium, have been proposed to explain this frequency dependence of AVP release. However, how either of these mechanisms would optimize release at any given frequency remains an open question. We have addressed this issue by correlating the frequency-dependence of intraterminal calcium dynamics and AVP release during action-potential stimulation. By monitoring the intraterminal calcium changes with low-affinity indicator dyes and millisecond time resolution, the signal could be dissected into three separate components: rapid Ca(2+) rises (Delta[Ca(2+)](tr)) related to action-potential depolarization, Ca(2+) extrusion and/or uptake, and a gradual increase in residual calcium (Delta[Ca(2+)](res)) throughout the stimulus train. Action-potential stimulation modulated all three components in a manner dependent on both the stimulation frequency and number of stimuli. Overall, the cumulative Delta[Ca(2+)](tr) amplitude initially increased with f(Stim) and then rapidly deteriorated, with a maximum around f(Stim)

  7. Dendritic spikes induce ripples in parvalbumin interneurons during hippocampal sharp waves.

    PubMed

    Chiovini, Balázs; Turi, Gergely F; Katona, Gergely; Kaszás, Attila; Pálfi, Dénes; Maák, Pál; Szalay, Gergely; Szabó, Mátyás Forián; Szabó, Gábor; Szadai, Zoltán; Káli, Szabolcs; Rózsa, Balázs

    2014-05-21

    Sharp-wave ripples are transient oscillatory events in the hippocampus that are associated with the reactivation of neuronal ensembles within specific circuits during memory formation. Fast-spiking, parvalbumin-expressing interneurons (FS-PV INs) are thought to provide fast integration in these oscillatory circuits by suppressing regenerative activity in their dendrites. Here, using fast 3D two-photon imaging and a caged glutamate, we challenge this classical view by demonstrating that FS-PV IN dendrites can generate propagating Ca(2+) spikes during sharp-wave ripples. The spikes originate from dendritic hot spots and are mediated dominantly by L-type Ca(2+) channels. Notably, Ca(2+) spikes were associated with intrinsically generated membrane potential oscillations. These oscillations required the activation of voltage-gated Na(+) channels, had the same frequency as the field potential oscillations associated with sharp-wave ripples, and controlled the phase of action potentials. Furthermore, our results demonstrate that the smallest functional unit that can generate ripple-frequency oscillations is a segment of a dendrite.

  8. Sodium-calcium exchange during the action potential in guinea-pig ventricular cells.

    PubMed Central

    Egan, T M; Noble, D; Noble, S J; Powell, T; Spindler, A J; Twist, V W

    1989-01-01

    1. Slow inward tail currents attributable to electrogenic sodium-calcium exchange can be recorded by imposing hyperpolarizing voltage clamp pulses during the normal action potential of isolated guinea-pig ventricular cells. The hyperpolarizations return the membrane to the resting potential (between -65 and -88 m V) allowing an inward current to be recorded. This current usually has peak amplitude when repolarization is imposed during the first 50 ms after the action potential upstroke, but becomes negligible once the final phase of repolarization is reached. The envelope of peak current tail amplitudes strongly resembles that of the intracellular calcium transient recorded in other studies. 2. Repetitive stimulation producing normal action potentials at a frequency of 2 Hz progressively augments the tail current recorded immediately after the stimulus train. Conversely, if each action potential is prematurely terminated at 0.1 Hz, repetitive stimulation produces a tail current much smaller than the control value. The control amplitude of inward current is only maintained if interrupted action potentials are separated by at least one full 'repriming' action potential. These effects mimic those on cell contraction (Arlock & Wohlfart, 1986) and suggest that progressive changes in tail current are controlled by variations in the amplitude and time course of the intracellular calcium transient. 3. When intracellular calcium is buffered sufficiently to abolish contraction, the tail current is abolished. Substitution of calcium with strontium greatly reduces the tail current. 4. The inward tail current can also be recorded at more positive membrane potentials using standard voltage clamp pulse protocols. In this way it was found that temperature has a large effect on the tail current, which can change from net inward at 22 degrees C to net outward at 37 degrees C. The largest inward currents are usually recorded at about 30 degrees C. It is shown that this effect is

  9. Two functional inhibitory circuits are comprised of a heterogeneous population of fast-spiking cortical interneurons.

    PubMed

    Li, P; Huntsman, M M

    2014-04-18

    Cortical fast spiking (FS) interneurons possess autaptic, synaptic, and electrical synapses that serve to mediate a fast, coordinated response to their postsynaptic targets. While FS interneurons are known to participate in numerous and diverse actions, functional subgroupings within this multi-functional interneuron class remain to be identified. In the present study, we examined parvalbumin-positive FS interneurons in layer 4 of the primary somatosensory (barrel) cortex - a brain region well-known for specialized inhibitory function. Here we show that FS interneurons fall into two broad categories identified by the onset of the first action potential in a depolarizing train as: "delayed firing FS interneurons (FSD) and early onset firing FS interneurons (FSE). Subtle variations in action potential firing reveal six subtypes within these two categories: delayed non-accommodating (FSD-NAC), delayed stuttering (FSD-STUT), early onset stuttering (FSE-STUT), early onset-late spiking (FSE-LS), early onset early-spiking (FSE-ES), and early onset accommodating (FSE-AC). Using biophysical criteria previously employed to distinguish neuronal cell types, the FSD and FSE categories exhibit several shared biophysical and synaptic properties that coincide with the notion of specificity of inhibitory function within the cortical FS interneuron class.

  10. Toward a system to measure action potential on mice brain slices with local magnetoresistive probes

    SciTech Connect

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastiao, A. M.

    2011-04-01

    This work combines an electrophysiological system with a magnetoresistive chip to measure the magnetic field created by the synaptic/action potential currents. The chip, with 15 spin valve sensors, was designed to be integrated in a recording chamber for submerged mice brain slices used for synaptic potential measurements. Under stimulation (rectangular pulses of 0.1 ms every 10 s) through a concentric electrode placed near the CA3/CA1 border of the hippocampus, the spin valve sensor readout signals with 20 {mu}V amplitude and a pulse length of 20 to 30 ms were recorded only in the pyramidal cell bodies region and can be interpreted as being derived from action potentials/currents.

  11. Toward a system to measure action potential on mice brain slices with local magnetoresistive probes

    NASA Astrophysics Data System (ADS)

    Amaral, J.; Cardoso, S.; Freitas, P. P.; Sebastião, A. M.

    2011-04-01

    This work combines an electrophysiological system with a magnetoresistive chip to measure the magnetic field created by the synaptic/action potential currents. The chip, with 15 spin valve sensors, was designed to be integrated in a recording chamber for submerged mice brain slices used for synaptic potential measurements. Under stimulation (rectangular pulses of 0.1 ms every 10 s) through a concentric electrode placed near the CA3/CA1 border of the hippocampus, the spin valve sensor readout signals with 20 μV amplitude and a pulse length of 20 to 30 ms were recorded only in the pyramidal cell bodies region and can be interpreted as being derived from action potentials/currents.

  12. Spike sorting of synchronous spikes from local neuron ensembles

    PubMed Central

    Pröpper, Robert; Alle, Henrik; Meier, Philipp; Geiger, Jörg R. P.; Obermayer, Klaus; Munk, Matthias H. J.

    2015-01-01

    Synchronous spike discharge of cortical neurons is thought to be a fingerprint of neuronal cooperativity. Because neighboring neurons are more densely connected to one another than neurons that are located further apart, near-synchronous spike discharge can be expected to be prevalent and it might provide an important basis for cortical computations. Using microelectrodes to record local groups of neurons does not allow for the reliable separation of synchronous spikes from different cells, because available spike sorting algorithms cannot correctly resolve the temporally overlapping waveforms. We show that high spike sorting performance of in vivo recordings, including overlapping spikes, can be achieved with a recently developed filter-based template matching procedure. Using tetrodes with a three-dimensional structure, we demonstrate with simulated data and ground truth in vitro data, obtained by dual intracellular recording of two neurons located next to a tetrode, that the spike sorting of synchronous spikes can be as successful as the spike sorting of nonoverlapping spikes and that the spatial information provided by multielectrodes greatly reduces the error rates. We apply the method to tetrode recordings from the prefrontal cortex of behaving primates, and we show that overlapping spikes can be identified and assigned to individual neurons to study synchronous activity in local groups of neurons. PMID:26289473

  13. Spiking neural network for recognizing spatiotemporal sequences of spikes

    NASA Astrophysics Data System (ADS)

    Jin, Dezhe Z.

    2004-02-01

    Sensory neurons in many brain areas spike with precise timing to stimuli with temporal structures, and encode temporally complex stimuli into spatiotemporal spikes. How the downstream neurons read out such neural code is an important unsolved problem. In this paper, we describe a decoding scheme using a spiking recurrent neural network. The network consists of excitatory neurons that form a synfire chain, and two globally inhibitory interneurons of different types that provide delayed feedforward and fast feedback inhibition, respectively. The network signals recognition of a specific spatiotemporal sequence when the last excitatory neuron down the synfire chain spikes, which happens if and only if that sequence was present in the input spike stream. The recognition scheme is invariant to variations in the intervals between input spikes within some range. The computation of the network can be mapped into that of a finite state machine. Our network provides a simple way to decode spatiotemporal spikes with diverse types of neurons.

  14. Restitution slope is principally determined by steady-state action potential duration.

    PubMed

    Shattock, Michael J; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela Wc; Niederer, Steve; MacLeod, Kenneth T; Winter, James

    2017-03-23

    AimsThe steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF.Methods and ResultsExperiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalising the restitution curve as a % of steady-state APD abolished the difference in restitution curves by all interventions. Altered restitution dynamics were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM, to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope.Conclusion(s)Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce

  15. Spiking Neurons for Analysis of Patterns

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terrance

    2008-01-01

    Artificial neural networks comprising spiking neurons of a novel type have been conceived as improved pattern-analysis and pattern-recognition computational systems. These neurons are represented by a mathematical model denoted the state-variable model (SVM), which among other things, exploits a computational parallelism inherent in spiking-neuron geometry. Networks of SVM neurons offer advantages of speed and computational efficiency, relative to traditional artificial neural networks. The SVM also overcomes some of the limitations of prior spiking-neuron models. There are numerous potential pattern-recognition, tracking, and data-reduction (data preprocessing) applications for these SVM neural networks on Earth and in exploration of remote planets. Spiking neurons imitate biological neurons more closely than do the neurons of traditional artificial neural networks. A spiking neuron includes a central cell body (soma) surrounded by a tree-like interconnection network (dendrites). Spiking neurons are so named because they generate trains of output pulses (spikes) in response to inputs received from sensors or from other neurons. They gain their speed advantage over traditional neural networks by using the timing of individual spikes for computation, whereas traditional artificial neurons use averages of activity levels over time. Moreover, spiking neurons use the delays inherent in dendritic processing in order to efficiently encode the information content of incoming signals. Because traditional artificial neurons fail to capture this encoding, they have less processing capability, and so it is necessary to use more gates when implementing traditional artificial neurons in electronic circuitry. Such higher-order functions as dynamic tasking are effected by use of pools (collections) of spiking neurons interconnected by spike-transmitting fibers. The SVM includes adaptive thresholds and submodels of transport of ions (in imitation of such transport in biological

  16. The effect of adrenaline on the temperature dependency of cardiac action potentials in pink salmon Oncorhynchus gorbuscha.

    PubMed

    Ballesta, S; Hanson, L M; Farrell, A P

    2012-04-01

    Using sharp electrode impalement, action potentials recorded from atrial and ventricular tissue of pink salmon Oncorhynchus gorbuscha generally decreased in duration with increasing test temperature (6, 10, 16 and 20° C). Stimulation of the tissue using 500 nM adrenaline had no significant effect on the duration of the atrial action potential at any test temperature but lengthened the ventricular action potential by ~17%.

  17. Variations in onset of action potential broadening: effects on calcium current studied in chick ciliary ganglion neurones.

    PubMed

    Pattillo, J M; Artim, D E; Simples, J E; Meriney, S D

    1999-02-01

    1. The voltage dependence and kinetic properties of stage 40 ciliary ganglion calcium currents were determined using short (10 ms) voltage steps. These properties aided the interpretation of the action potential-evoked calcium current described below, and the comparison of our data with those observed in other preparations. 2. Three different natural action potential waveforms were modelled by a series of ramps to generate voltage clamp commands. Calcium currents evoked by these model action potentials were compared before and after alterations in the repolarization phase of each action potential. 3. Abrupt step repolarizations from various time points were used to estimate the time course of calcium current activation during each action potential. Calcium current evoked by fast action potentials (duration at half-amplitude, 0.5 or 1.0 ms) did not reach maximal activation until the action potential had repolarized by 40-50 %. In contrast, calcium current evoked by a slow action potential (duration at half-amplitude, 2.2 ms) was maximally activated near the peak of the action potential. 4. Slowing the rate of repolarization of the action potential (broadening) from different times was used to examine effects on peak and total calcium influx. With all three waveforms tested, broadening consistently increased total calcium influx (integral). However, peak calcium current was either increased or decreased depending on the duration of the control action potential tested and the specific timing of the initiation of broadening the repolarization phase. 5. The opposite effects on peak calcium current observed with action potential broadening beginning at different time points in repolarization may provide a mechanism for the variable effects of potassium channel blockers on transmitter release magnitude.

  18. Ischemia deteriorates the spike encoding of rat cerebellar Purkinje cells by raising intracellular Ca{sup 2+}

    SciTech Connect

    Zhao Shidi; Chen Na; Yang Zhilai; Huang Li; Zhu Yan; Guan Sudong; Chen Qianfen; Wang Jinhui

    2008-02-08

    Ischemia-induced excitotoxicity at cerebellar Purkinje cells is presumably due to a persistent glutamate action. To the fact that they are more vulnerable to ischemia than other glutamate-innervated neurons, we studied whether additional mechanisms are present and whether cytoplasm Ca{sup 2+} plays a key role in their ischemic excitotoxicity. Ischemic changes in the excitability of Purkinje cells were measured by whole-cell recording in cerebellar slices of rats with less glutamate action. The role of cytoplasm Ca{sup 2+} was examined by two-photon cellular imaging and BAPTA infusion in Purkinje cells. Lowering perfusion rate to cerebellar slices deteriorated spike timing and raised spike capacity of Purkinje cells. These changes were associated with the reduction of spike refractory periods and threshold potentials, as well as the loss of their control to spike encoding. Ischemia-induced functional deterioration at Purkinje neurons was accompanied by cytoplasm Ca{sup 2+} rise and prevented by BAPTA infusion. Therefore, the ischemia destabilizes the spike encoding of Purkinje cells via raising cytoplasm Ca{sup 2+} without a need for glutamate, which subsequently causes their excitotoxic death.

  19. Modeling the calcium spike as a threshold triggered fixed waveform for synchronous inputs in the fluctuation regime

    PubMed Central

    Chua, Yansong; Morrison, Abigail; Helias, Moritz

    2015-01-01

    Modeling the layer 5 pyramidal neuron as a system of three connected isopotential compartments, the soma, proximal, and distal compartment, with calcium spike dynamics in the distal compartment following first order kinetics, we are able to reproduce in-vitro experimental results which demonstrate the involvement of calcium spikes in action potentials generation. To explore how calcium spikes affect the neuronal output in-vivo, we emulate in-vivo like conditions by embedding the neuron model in a regime of low background fluctuations with occasional large synchronous inputs. In such a regime, a full calcium spike is only triggered by the synchronous events in a threshold like manner and has a stereotypical waveform. Hence, in such a regime, we are able to replace the calcium dynamics with a simpler threshold triggered current of fixed waveform, which is amenable to analytical treatment. We obtain analytically the mean somatic membrane potential excursion due to a calcium spike being triggered while in the fluctuating regime. Our analytical form that accounts for the covariance between conductances and the membrane potential shows a better agreement with simulation results than a naive first order approximation. PMID:26283954

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

    PubMed

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi

    2013-04-26

    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 compound 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 IC50 values of 1.2 and 1.5mM, 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; IC50=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.

  1. Consensus-Based Sorting of Neuronal Spike Waveforms

    PubMed Central

    Fournier, Julien; Mueller, Christian M.; Shein-Idelson, Mark; Hemberger, Mike

    2016-01-01

    Optimizing spike-sorting algorithms is difficult because sorted clusters can rarely be checked against independently obtained “ground truth” data. In most spike-sorting algorithms in use today, the optimality of a clustering solution is assessed relative to some assumption on the distribution of the spike shapes associated with a particular single unit (e.g., Gaussianity) and by visual inspection of the clustering solution followed by manual validation. When the spatiotemporal waveforms of spikes from different cells overlap, the decision as to whether two spikes should be assigned to the same source can be quite subjective, if it is not based on reliable quantitative measures. We propose a new approach, whereby spike clusters are identified from the most consensual partition across an ensemble of clustering solutions. Using the variability of the clustering solutions across successive iterations of the same clustering algorithm (template matching based on K-means clusters), we estimate the probability of spikes being clustered together and identify groups of spikes that are not statistically distinguishable from one another. Thus, we identify spikes that are most likely to be clustered together and therefore correspond to consistent spike clusters. This method has the potential advantage that it does not rely on any model of the spike shapes. It also provides estimates of the proportion of misclassified spikes for each of the identified clusters. We tested our algorithm on several datasets for which there exists a ground truth (simultaneous intracellular data), and show that it performs close to the optimum reached by a support vector machine trained on the ground truth. We also show that the estimated rate of misclassification matches the proportion of misclassified spikes measured from the ground truth data. PMID:27536990

  2. Simple techniques suitable for student use to record action potentials from the frog heart.

    PubMed

    Yoshida, S

    2001-12-01

    Demonstrating action potentials during class experiments is very educational for science students. It is not easy, however, to obtain a stable intracellular recording of action potentials from the conventionally used skeletal muscle cells, because the tip of a glass microelectrode often comes out or breaks due to muscle contraction. Here, I present a much simpler recording method using a flexible polyethylene electrode with a wide orifice (approximately 1 mm) for a bullfrog heart beating on automaticity. Extracellular recordings of action potentials (electrocardiogram) can be obtained by placing an electrode on the cardiac surface, and transmembrane potentials can be obtained by rupturing the membrane with negative pressure, i.e., whole cell configuration. Once attached to the heart by suction, the polyethylene electrode does not easily come off during contraction of the heart. Perfusion of the heart via the postcaval vein offers us opportunities for observing the effects of either changing ionic compositions of solutions or applying drugs. The techniques shown here provide a simple and convenient way to perform a variety of class experiments.

  3. Transient enhancement of spike-evoked calcium signaling by a serotonergic interneuron.

    PubMed

    Hill, Evan S; Sakurai, Akira; Katz, Paul S

    2008-11-01

    Enhancement of presynaptic Ca(2+) signals is widely recognized as a potential mechanism for heterosynaptic potentiation of neurotransmitter release. Here we show that stimulation of a serotonergic interneuron increased spike-evoked Ca(2+) in a manner consistent with its neuromodulatory effect on synaptic transmission. In the gastropod mollusk, Tritonia diomedea, stimulation of a serotonergic dorsal swim interneuron (DSI) at physiological rates heterosynaptically enhances the strength of output synapses made by another swim interneuron, C2, onto neurons in the pedal ganglion. Using intracellular electrophysiological recording combined with real-time confocal imaging of C2 (loaded with Oregon Green Bapta 1), it was determined that DSI stimulation increases the amplitude of spike-evoked Ca(2+) signals in C2 without altering basal Ca(2+) signals. This neuromodulatory action was restricted to distal neurites of C2 where synapses with pedal neurons are located. The effect of DSI stimulation on C2 spike-evoked Ca(2+) signals resembled DSI heterosynaptic enhancement of C2 synapses in several measures: both decayed within 15 s, both were abolished by the serotonin receptor antagonist, methysergide, and both were independent of DSI's depolarizing actions on C2. A brief puff of serotonin could mimic the enhancement of spike-evoked Ca(2+) signals in the distal neurites of C2, but larger puffs or bath-applied serotonin elicited nonphysiological effects. These results suggest that DSI heterosynaptic enhancement of C2 synaptic strength may be mediated by a local enhancement of spike-evoked Ca(2+) signals in the distal neurites of C2.

  4. On Spike-Timing-Dependent-Plasticity, Memristive Devices, and Building a Self-Learning Visual Cortex

    PubMed Central

    Zamarreño-Ramos, Carlos; Camuñas-Mesa, Luis A.; Pérez-Carrasco, Jose A.; Masquelier, Timothée; Serrano-Gotarredona, Teresa; Linares-Barranco, Bernabé

    2011-01-01

    In this paper we present a very exciting overlap between emergent nanotechnology and neuroscience, which has been discovered by neuromorphic engineers. Specifically, we are linking one type of memristor nanotechnology devices to the biological synaptic update rule known as spike-time-dependent-plasticity (STDP) found in real biological synapses. Understanding this link allows neuromorphic engineers to develop circuit architectures that use this type of memristors to artificially emulate parts of the visual cortex. We focus on the type of memristors referred to as voltage or flux driven memristors and focus our discussions on a behavioral macro-model for such devices. The implementations result in fully asynchronous architectures with neurons sending their action potentials not only forward but also backward. One critical aspect is to use neurons that generate spikes of specific shapes. We will see how by changing the shapes of the neuron action potential spikes we can tune and manipulate the STDP learning rules for both excitatory and inhibitory synapses. We will see how neurons and memristors can be interconnected to achieve large scale spiking learning systems, that follow a type of multiplicative STDP learning rule. We will briefly extend the architectures to use three-terminal transistors with similar memristive behavior. We will illustrate how a V1 visual cortex layer can assembled and how it is capable of learning to extract orientations from visual data coming from a real artificial CMOS spiking retina observing real life scenes. Finally, we will discuss limitations of currently available memristors. The results presented are based on behavioral simulations and do not take into account non-idealities of devices and interconnects. The aim of this paper is to present, in a tutorial manner, an initial framework for the possible development of fully asynchronous STDP learning neuromorphic architectures exploiting two or three-terminal memristive type devices

  5. The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells

    PubMed Central

    Shao, Li-Rong; Halvorsrud, Ragnhild; Borg-Graham, Lyle; Storm, Johan F

    1999-01-01

    The role of large-conductance Ca2+-dependent K+ channels (BK-channels; also known as maxi-K- or slo-channels) in spike broadening during repetitive firing was studied in CA1 pyramidal cells, using sharp electrode intracellular recordings in rat hippocampal slices, and computer modelling. Trains of action potentials elicited by depolarizing current pulses showed a progressive, frequency-dependent spike broadening, reflecting a reduced rate of repolarization. During a 50 ms long 5 spike train, the spike duration increased by 63·6 ± 3·4% from the 1st to the 3rd spike. The amplitude of the fast after-hyperpolarization (fAHP) also rapidly declined during each train. Suppression of BK-channel activity with (a) the selective BK-channel blocker iberiotoxin (IbTX, 60 nM), (b) the non-peptidergic BK-channel blocker paxilline (2–10 μM), or (c) calcium-free medium, broadened the 1st spike to a similar degree (≈60%). BK-channel suppression also caused a similar change in spike waveform as observed during repetitive firing, and eliminated (occluded) most of the spike broadening during repetitive firing. Computer simulations using a reduced compartmental model with transient BK-channel current and 10 other active ionic currents, produced an activity-dependent spike broadening that was strongly reduced when the BK-channel inactivation mechanism was removed. These results, which are supported by recent voltage-clamp data, strongly suggest that in CA1 pyramidal cells, fast inactivation of a transient BK-channel current (ICT), substantially contributes to frequency-dependent spike broadening during repetitive firing. PMID:10562340

  6. A spiking neuron circuit based on a carbon nanotube transistor.

    PubMed

    Chen, C-L; Kim, K; Truong, Q; Shen, A; Li, Z; Chen, Y

    2012-07-11

    A spiking neuron circuit based on a carbon nanotube (CNT) transistor is presented in this paper. The spiking neuron circuit has a crossbar architecture in which the transistor gates are connected to its row electrodes and the transistor sources are connected to its column electrodes. An electrochemical cell is incorporated in the gate of the transistor by sandwiching a hydrogen-doped poly(ethylene glycol)methyl ether (PEG) electrolyte between the CNT channel and the top gate electrode. An input spike applied to the gate triggers a dynamic drift of the hydrogen ions in the PEG electrolyte, resulting in a post-synaptic current (PSC) through the CNT channel. Spikes input into the rows trigger PSCs through multiple CNT transistors, and PSCs cumulate in the columns and integrate into a 'soma' circuit to trigger output spikes based on an integrate-and-fire mechanism. The spiking neuron circuit can potentially emulate biological neuron networks and their intelligent functions.

  7. Non-fibrillar beta-amyloid abates spike-timing-dependent synaptic potentiation at excitatory synapses in layer 2/3 of the neocortex by targeting postsynaptic AMPA receptors.

    PubMed

    Shemer, Isaac; Holmgren, Carl; Min, Rogier; Fülöp, Livia; Zilberter, Misha; Sousa, Kyle M; Farkas, Tamás; Härtig, Wolfgang; Penke, Botond; Burnashev, Nail; Tanila, Heikki; Zilberter, Yuri; Harkany, Tibor

    2006-04-01

    Cognitive decline in Alzheimer's disease (AD) stems from the progressive dysfunction of synaptic connections within cortical neuronal microcircuits. Recently, soluble amyloid beta protein oligomers (Abeta(ol)s) have been identified as critical triggers for early synaptic disorganization. However, it remains unknown whether a deficit of Hebbian-related synaptic plasticity occurs during the early phase of AD. Therefore, we studied whether age-dependent Abeta accumulation affects the induction of spike-timing-dependent synaptic potentiation at excitatory synapses on neocortical layer 2/3 (L2/3) pyramidal cells in the APPswe/PS1dE9 transgenic mouse model of AD. Synaptic potentiation at excitatory synapses onto L2/3 pyramidal cells was significantly reduced at the onset of Abeta pathology and was virtually absent in mice with advanced Abeta burden. A decreased alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/N-methyl-D-aspartate (NMDA) receptor-mediated current ratio implicated postsynaptic mechanisms underlying Abeta synaptotoxicity. The integral role of Abeta(ol)s in these processes was verified by showing that pretreatment of cortical slices with Abeta((25-35)ol)s disrupted spike-timing-dependent synaptic potentiation at unitary connections between L2/3 pyramidal cells, and reduced the amplitude of miniature excitatory postsynaptic currents therein. A robust decrement of AMPA, but not NMDA, receptor-mediated currents in nucleated patches from L2/3 pyramidal cells confirmed that Abeta(ol)s perturb basal glutamatergic synaptic transmission by affecting postsynaptic AMPA receptors. Inhibition of AMPA receptor desensitization by cyclothiazide significantly increased the amplitude of excitatory postsynaptic potentials evoked by afferent stimulation, and rescued synaptic plasticity even in mice with pronounced Abeta pathology. We propose that soluble Abeta(ol)s trigger the diminution of synaptic plasticity in neocortical pyramidal cell networks during early

  8. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-09

    With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension.

  9. Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater.

    PubMed

    Brown, Daniel J; Patuzzi, Robert B

    2010-08-01

    We have investigated the generation of the compound action potential (CAP) from the auditory nerve of guinea pigs. Responses to acoustic tone-bursts were recorded from the round window (RW), throughout the cochlear fluids, from the surface of the cochlear nucleus, from the central end of the auditory nerve after removal of the cochlear nucleus, from the scalp vertex, and from the contralateral ear. Responses were compared before, during and after experimental manipulations including pharmacological blockade of the auditory nerve, section of the auditory nerve, section of the efferent nerves, removal of the cochlear nucleus, and focal cooling of the cochlear nerve and/or cochlear nucleus. Regardless of the waveform changes occurring with these manipulations, the responses were similar in waveform but inverted polarity across the internal auditory meatus. The CAP waveforms were very similar before and after removal of the cochlear nucleus, apart from transient changes that could last many minutes. This suggests that the main CAP components are generated entirely by the eighth nerve. Based on previous studies and a clear understanding of the generation of extracellular potentials, we suggest that the early components in the responses recorded from the round window, from the cochlear fluids, from the surface of the cochlear nucleus, or from the scalp are a far-field or stationary potential, generated when the circulating action currents associated with each auditory neurone encounters a high extracellular resistance as it passes through the dura mater.

  10. Dopaminergic modulation of short-term synaptic plasticity in fast-spiking interneurons of primate dorsolateral prefrontal cortex.

    PubMed

    Gonzalez-Burgos, G; Kroener, S; Seamans, J K; Lewis, D A; Barrionuevo, G

    2005-12-01

    Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms of dopamine neuromodulation in PFC are not well understood. We have studied the effects of dopamine receptor activation during persistent stimulation of excitatory inputs onto fast-spiking GABAergic interneurons in monkey PFC. Stimulation at 20 Hz induced short-term excitatory postsynaptic potential (EPSP) depression. The D1 receptor agonist SKF81297 (5 microM) significantly reduced the amplitude of the first EPSP but not of subsequent responses in EPSP trains, which still displayed significant depression. Dopamine (DA; 10 microM) effects were similar to those of SKF81297 and were abolished by the D1 antagonist SCH23390 (5 microM), indicating a D1 receptor-mediated effect. DA did not alter miniature excitatory postsynaptic currents, suggesting that its effects were activity dependent and presynaptic action potential dependent. In contrast to previous findings in pyramidal neurons, in fast-spiking cells, contribution of N-methyl-D-aspartate receptors to EPSPs at subthreshold potentials was not significant and fast-spiking cell depolarization decreased EPSP duration. In addition, DA had no significant effects on temporal summation. The selective decrease in the amplitude of the first EPSP in trains delivered every 10 s suggests that in fast-spiking neurons, DA reduces the amplitude of EPSPs evoked at low frequency but not of EPSPs evoked by repetitive stimulation. DA may therefore improve detection of EPSP bursts above background synaptic activity. EPSP bursts displaying short-term depression may transmit spike-timing-dependent temporal codes contained in presynaptic spike trains. Thus DA neuromodulation may increase the signal-to-noise ratio at fast-spiking cell inputs.

  11. Modeling the attenuation and failure of action potentials in the dendrites of hippocampal neurons.

    PubMed Central

    Migliore, M

    1996-01-01

    We modeled two different mechanisms, a shunting conductance and a slow sodium inactivation, to test whether they could modulate the active propagation of a train of action potentials in a dendritic tree. Computer simulations, using a compartmental model of a pyramidal neuron, suggest that each of these two mechanisms could account for the activity-dependent attenuation and failure of the action potentials in the dendrites during the train. Each mechanism is shown to be in good qualitative agreement with experimental findings on somatic or dendritic stimulation and on the effects of hyperpolarization. The conditions under which branch point failures can be observed, and a few experimentally testable predictions, are presented and discussed. PMID:8913580

  12. Regulation of cough and action potentials by voltage-gated Na channels.

    PubMed

    Carr, Michael J

    2013-10-01

    The classical role ascribed to voltage-gated Na channels is the conduction of action potentials. Some excitable tissues such as cardiac muscle and skeletal muscle predominantly express a single voltage-gated Na channels isoform. Of the nine voltage-gated Na channels, seven are expressed in neurons, of these Nav 1.7, 1.8 and 1.9 are expressed in sensory neurons including vagal sensory neurons that innervate the airways and initiate cough. Nav 1.7 and Nav 1.9 are of particular interest as they represent two extremes in the functional diversity of voltage-gated Na channels. Voltage-gated Na channel isoforms expressed in airway sensory neurons produce multiple distinct Na currents that underlie distinct aspects of sensory neuron function. The interaction between voltage-gated Na currents underlies the characteristic ability of airway sensory nerves to encode encounters with irritant stimuli into action potential discharge and evoke the cough reflex.

  13. Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites.

    PubMed

    Bakkum, Douglas J; Frey, Urs; Radivojevic, Milos; Russell, Thomas L; Müller, Jan; Fiscella, Michele; Takahashi, Hirokazu; Hierlemann, Andreas

    2013-01-01

    Axons are traditionally considered stable transmission cables, but evidence of the regulation of action potential propagation demonstrates that axons may have more important roles. However, their small diameters render intracellular recordings challenging, and low-magnitude extracellular signals are difficult to detect and assign. Better experimental access to axonal function would help to advance this field. Here we report methods to electrically visualize action potential propagation and network topology in cortical neurons grown over custom arrays, which contain 11,011 microelectrodes and are fabricated using complementary metal oxide semiconductor technology. Any neuron lying on the array can be recorded at high spatio-temporal resolution, and simultaneously precisely stimulated with little artifact. We find substantial velocity differences occurring locally within single axons, suggesting that the temporal control of a neuron's output may contribute to neuronal information processing.

  14. Risperidone prolongs cardiac action potential through reduction of K+ currents in rabbit myocytes.

    PubMed

    Gluais, Pascale; Bastide, Michèle; Caron, Jacques; Adamantidis, Monique

    2002-05-31

    Prolongation of QT interval by antipsychotic drugs is an unwanted side effect that may lead to ventricular arrhythmias. The antipsychotic agent risperidone has been shown to cause QT prolongation, especially in case of overdosage. We investigated risperidone effects on action potentials recorded from rabbit Purkinje fibers and ventricular myocardium and on potassium currents recorded from atrial and ventricular rabbit isolated myocytes. The results showed that (1) risperidone (0.1-3 microM) exerted potent lengthening effects on action potential duration in both tissues with higher potency in Purkinje fibers and caused the development of early afterdepolarizations at low stimulation rate; (2) risperidone (0.03-0.3 microM) reduced significantly the current density of the delayed rectifier current and at 30 microM decreased the transient outward and the inward rectifier currents. This study might explain QT prolongation observed in some patients treated with risperidone and gives enlightenment on the risk of cardiac adverse events.

  15. Real-time imaging of action potentials in nerves using changes in birefringence

    PubMed Central

    Badreddine, Ali H.; Jordan, Tomas; Bigio, Irving J.

    2016-01-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time “movies”. This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

  16. A mathematical model of action potential in cells of vascular plants.

    PubMed

    Sukhov, Vladimir; Vodeneev, Vladimir

    2009-12-01

    A mathematical model of action potential (AP) in vascular plants cells has been worked out. The model takes into account actions of plasmalemma ion transport systems (K(+), Cl(-) and Ca(2+) channels; H(+)- and Ca(2+)-ATPases; 2H(+)/Cl(-) symporter; and H(+)/K(+) antiporter), changes of ion concentrations in the cell and in the extracellular space, cytoplasmic and apoplastic buffer capacities and the temperature dependence of active transport systems. The model of AP simulates a stationary level of the membrane potential and ion concentrations, generation of AP induced by electrical stimulation and gradual cooling and the impact of external Ca(2+) for AP development. The model supports a hypothesis about participation of H(+)-ATPase in AP generation.

  17. Monophasic action potentials in a patient with multiform ventricular tachycardia without QT prolongation.

    PubMed Central

    Emori, T; Ohe, T; Shimomura, K

    1993-01-01

    A 41 year old woman had multiform ventricular tachycardia without QT prolongation. Monophasic action potentials were recorded from the right ventricle during the attacks of multiform ventricular tachycardia and effective refractory periods were examined at the same sites. There was no abnormal hump to suggest early afterdepolarisation in the monophasic action potentials, but there was dispersion of the effective refractory period in the right ventricle (80 ms). Stimulation from the right ventricular apex, where the effective refractory period was shortest, reproducibly induced multiform ventricular tachycardia. Two weeks after admission, when her condition was stable, multiform ventricular tachycardia could not be induced and the dispersion of the effective refractory period in the right ventricle was 20 ms. PMID:8489870

  18. Spike Phase Locking in CA1 Pyramidal Neurons depends on Background Conductance and Firing Rate

    PubMed Central

    Broiche, Tilman; Malerba, Paola; Dorval, Alan D.; Borisyuk, Alla; Fernandez, Fernando R.; White, John A.

    2012-01-01

    Oscillatory activity in neuronal networks correlates with different behavioral states throughout the nervous system, and the frequency-response characteristics of individual neurons are believed to be critical for network oscillations. Recent in vivo studies suggest that neurons experience periods of high membrane conductance, and that action potentials are often driven by membrane-potential fluctuations in the living animal. To investigate the frequency-response characteristics of CA1 pyramidal neurons in the presence of high conductance and voltage fluctuations, we performed dynamic-clamp experiments in rat hippocampal brain slices. We drove neurons with noisy stimuli that included a sinusoidal component ranging, in different trials, from 0.1 to 500 Hz. In subsequent data analysis, we determined action potential phase-locking profiles with respect to background conductance, average firing rate, and frequency of the sinusoidal component. We found that background conductance and firing rate qualitatively change the phase-locking profiles of CA1 pyramidal neurons vs. frequency. In particular, higher average spiking rates promoted band-pass profiles, and the high-conductance state promoted phase-locking at frequencies well above what would be predicted from changes in the membrane time constant. Mechanistically, spike-rate adaptation and frequency resonance in the spike-generating mechanism are implicated in shaping the different phase-locking profiles. Our results demonstrate that CA1 pyramidal cells can actively change their synchronization properties in response to global changes in activity associated with different behavioral states. PMID:23055508

  19. Antisense suppression of potassium channel expression demonstrates its role in maturation of the action potential.

    PubMed

    Vincent, A; Lautermilch, N J; Spitzer, N C

    2000-08-15

    A developmental increase in delayed rectifier potassium current (I(Kv)) in embryonic Xenopus spinal neurons is critical for the maturation of excitability and action potential waveform. Identifying potassium channel genes that generate I(Kv) is essential to understanding the mechanisms by which they are controlled. Several Kv genes are upregulated during embryogenesis in parallel with increases in I(Kv) and produce delayed rectifier current when heterologously expressed, indicating that they could encode channels underlying this current. We used antisense (AS) cRNA to test the contribution of xKv3.1 to the maturation of I(Kv), because xKv3.1 AS appears to suppress specifically heterologous expression of potassium current by xKv3.1 mRNA. The injection of xKv3.1 AS into embryos reduces endogenous levels of xKv3.1 mRNA in the developing spinal cord and reduces the amplitude and rate of activation of I(Kv) in 40% of cultured neurons, similar to the percentage of neurons in which endogenous xKv3.1 transcripts are detected. The current in these mature neurons resembles that at an earlier stage of differentiation before the appearance of xKv3.1 mRNA. Furthermore, AS expression increases the duration of the action potential in 40% of the neurons. No change in voltage-dependent calcium current is observed, suggesting that the decrease in I(Kv) is sufficient to account for lengthening of the action potential. Computer-simulated action potentials incorporating observed reductions in amplitude and rate of activation of I(Kv) exhibit an increase in duration similar to that observed experimentally. Thus xKv3.1 contributes to the maturation of I(Kv) in a substantial percentage of these developing spinal neurons.

  20. Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation.

    PubMed

    Terrenoire, Cecile; Clancy, Colleen E; Cormier, Joseph W; Sampson, Kevin J; Kass, Robert S

    2005-03-18

    I(Ks), the slowly activating component of the delayed rectifier current, plays a major role in repolarization of the cardiac action potential (AP). Genetic mutations in the alpha- (KCNQ1) and beta- (KCNE1) subunits of I(Ks) underlie Long QT Syndrome type 1 and 5 (LQT-1 and LQT-5), respectively, and predispose carriers to the development of polymorphic ventricular arrhythmias and sudden cardiac death. beta-adrenergic stimulation increases I(Ks) and results in rate dependent AP shortening, a control system that can be disrupted by some mutations linked to LQT-1 and LQT-5. The mechanisms by which I(Ks) regulates action potential duration (APD) during beta-adrenergic stimulation at different heart rates are not known, nor are the consequences of mutation induced disruption of this regulation. Here we develop a complementary experimental and theoretical approach to address these questions. We reconstituted I(Ks) in CHO cells (ie, KCNQ1 coexpressed with KCNE1 and the adaptator protein Yotiao) and quantitatively examined the effects of beta-adrenergic stimulation on channel kinetics. We then developed theoretical models of I(Ks) in the absence and presence of beta-adrenergic stimulation. We simulated the effects of sympathetic stimulation on channel activation (speeding) and deactivation (slowing) kinetics on the whole cell action potential under different pacing conditions. The model suggests these kinetic effects are critically important in rate-dependent control of action potential duration. We also investigate the effects of two LQT-5 mutations that alter kinetics and impair sympathetic stimulation of I(Ks) and show the likely mechanism by which they lead to tachyarrhythmias and indicate a distinct role of I(KS) kinetics in this electrical dysfunction. The full text of this article is available online at http://circres.ahajournals.org.

  1. Contributions of HERG K+ current to repolarization of the human ventricular action potential.

    PubMed

    Fink, Martin; Noble, Denis; Virag, Laszlo; Varro, Andras; Giles, Wayne R

    2008-01-01

    Action potential repolarization in the mammalian heart is governed by interactions of a number of time- and voltage-dependent channel-mediated currents, as well as contributions from the Na+/Ca2+ exchanger and the Na+/K+ pump. Recent work has shown that one of the K+ currents (HERG) which contributes to repolarization in mammalian ventricle is a locus at which a number of point mutations can have significant functional consequences. In addition, the remarkable sensitivity of this K+ channel isoform to inhibition by a variety of pharmacological agents and clinical drugs has resulted in HERG being a major focus for Safety Pharmacology requirements. For these reasons we and others have attempted to define the functional role for HERG-mediated K+ currents in repolarization of the action potential in the human ventricle. Here, we describe and evaluate changes in the formulations for two K+ currents, IK1 and HERG (or IK,r), within the framework of ten Tusscher model of the human ventricular action potential. In this computational study, new mathematical formulations for the two nonlinear K+ conductances, IK1 and HERG, have been developed based upon experimental data obtained from electrophysiological studies of excised human ventricular tissue and/or myocytes. The resulting mathematical model provides much improved simulations of the relative sizes and time courses of the K+ currents which modulate repolarization. Our new formulation represents an important first step in defining the mechanism(s) of repolarization of the membrane action potential in the human ventricle. Our overall goal is to understand the genesis of the T-wave of the human electrocardiogram.

  2. Effects of ropinirole on action potential characteristics and the underlying ion currents in canine ventricular myocytes.

    PubMed

    Simkó, József; Szentandrássy, Norbert; Harmati, Gábor; Bárándi, László; Horváth, Balázs; Magyar, János; Bányász, Tamás; Lorincz, István; Nánási, Péter P

    2010-09-01

    In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the dopamine receptor agonist ropinirole. In the present study, therefore, the concentration-dependent effects of ropinirole on action potential morphology and the underlying ion currents were studied in enzymatically dispersed canine ventricular cardiomyocytes using standard microelectrode, conventional whole-cell patch clamp, and action potential voltage clamp techniques. At concentrations > or = 1 microM, ropinirole increased action potential duration (APD(90)) and suppressed the rapid delayed rectifier K(+) current (I (Kr)) with an IC(50) value of 2.7 +/- 0.25 microM and Hill coefficient of 0.92 +/- 0.09. The block increased with increasing depolarizations to more positive voltages, but paradoxically, the activation of I (Kr) was accelerated by 3 muM ropinirole (time constant decreased from 34 +/- 4 to 14 +/- 1 ms). No significant changes in the fast and slow deactivation time constants were observed with ropinirole. At higher concentrations, ropinirole decreased the amplitude of early repolarization (at concentrations > or = 10 microM), reduced the maximum rate of depolarization and caused depression of the plateau (at concentrations > or = 30 microM), and shortened APD measured at 50% repolarization (at 300 microM) indicating a concentration-dependent inhibition of I (to), I (Na), and I (Ca). Suppression of I (Kr), I (to), and I (Ca) has been confirmed under conventional patch clamp and action potential voltage clamp conditions. I (Ks) and I (K1) were not influenced significantly by ropinirole at concentrations less than 300 microM. All these effects of ropinirole were fully reversible upon washout. The results indicate that ropinirole treatment may carry proarrhythmic risk for patients with inherited or acquired long QT syndrome due to inhibition of I (Kr)-especially in cases of accidental overdose or intoxication.

  3. Application of the optical method in experimental cardiology: action potential and intracellular calcium concentration measurement.

    PubMed

    Ronzhina, M; Cmiel, V; Janoušek, O; Kolářová, J; Nováková, M; Babula, P; Provazník, I

    2013-01-01

    It has been shown that, in addition to conventional contact electrode techniques, optical methods using fluorescent dyes can be successfully used for cardiac signal measurement. In this review, the physical and technical fundamentals of the method are described, as well as the properties of the most common systems for measuring action potentials and intracellular calcium concentration. Special attention is paid to summarizing limitations and trends in developing this method.

  4. Beyond faithful conduction: short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon.

    PubMed

    Bucher, Dirk; Goaillard, Jean-Marc

    2011-09-01

    Most spiking neurons are divided into functional compartments: a dendritic input region, a soma, a site of action potential initiation, an axon trunk and its collaterals for propagation of action potentials, and distal arborizations and terminals carrying the output synapses. The axon trunk and lower order branches are probably the most neglected and are often assumed to do nothing more than faithfully conducting action potentials. Nevertheless, there are numerous reports of complex membrane properties in non-synaptic axonal regions, owing to the presence of a multitude of different ion channels. Many different types of sodium and potassium channels have been described in axons, as well as calcium transients and hyperpolarization-activated inward currents. The complex time- and voltage-dependence resulting from the properties of ion channels can lead to activity-dependent changes in spike shape and resting potential, affecting the temporal fidelity of spike conduction. Neural coding can be altered by activity-dependent changes in conduction velocity, spike failures, and ectopic spike initiation. This is true under normal physiological conditions, and relevant for a number of neuropathies that lead to abnormal excitability. In addition, a growing number of studies show that the axon trunk can express receptors to glutamate, GABA, acetylcholine or biogenic amines, changing the relative contribution of some channels to axonal excitability and therefore rendering the contribution of this compartment to neural coding conditional on the presence of neuromodulators. Long-term regulatory processes, both during development and in the context of activity-dependent plasticity may also affect axonal properties to an underappreciated extent.

  5. Beyond faithful conduction: short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon

    PubMed Central

    Bucher, Dirk; Goaillard, Jean-Marc

    2011-01-01

    Most spiking neurons are divided into functional compartments: a dendritic input region, a soma, a site of action potential initiation, an axon trunk and its collaterals for propagation of action potentials, and distal arborizations and terminals carrying the output synapses. The axon trunk and lower order branches are probably the most neglected and are often assumed to do nothing more than faithfully conducting action potentials. Nevertheless, there are numerous reports of complex membrane properties in non-synaptic axonal regions, owing to the presence of a multitude of different ion channels. Many different types of sodium and potassium channels have been described in axons, as well as calcium transients and hyperpolarization-activated inward currents. The complex time- and voltage-dependence resulting from the properties of ion channels can lead to activity-dependent changes in spike shape and resting potential, affecting the temporal fidelity of spike conduction. Neural coding can be altered by activity-dependent changes in conduction velocity, spike failures, and ectopic spike initiation. This is true under normal physiological conditions, and relevant for a number of neuropathies that lead to abnormal excitability. In addition, a growing number of studies show that the axon trunk can express receptors to glutamate, GABA, acetylcholine or biogenic amines, changing the relative contribution of some channels to axonal excitability and therefore rendering the contribution of this compartment to neural coding conditional on the presence of neuromodulators. Long-term regulatory processes, both during development and in the context of activity-dependent plasticity may also affect axonal properties to an underappreciated extent. PMID:21708220

  6. Hebbian spike-timing dependent plasticity at the cerebellar input stage.

    PubMed

    Sgritta, M; Locatelli, F; Soda, T; Prestori, F; D'Angelo, E

    2017-02-10

    Spike-timing dependent plasticity (STDP) is a form of long-term synaptic plasticity exploiting the time relationship between postsynaptic action potentials (AP) and EPSPs. Surprisingly enough, very little was known about STDP in the cerebellum, although it is thought to play a critical role for learning appropriate timing of actions. We speculated that low-frequency oscillations observed in the granular layer may provide a reference for repetitive EPSP/AP phase coupling. Here we show that EPSP-spike pairing at 6Hz can optimally induce STDP at the mossy fiber - granule cell synapse in rats. Spike timing-dependent long-term potentiation and depression (st-LTP and st-LTD) were confined to a ±25 ms time-window. Since EPSPs led APs in st-LTP while APs led EPSPs in st-LTD, STDP was Hebbian in nature. STDP occurred at 6-10 Hz but vanished above 50 Hz or below 1 Hz (where only LTP or LTD occurred). STDP disappeared with randomized EPSP/AP pairing or high intracellular Ca(2+) buffering and its sign was inverted by GABA-A receptor activation. Both st-LTP and st-LTD required NMDA receptors, but st-LTP also required reinforcing signals mediated by mGluRs and intracellular calcium stores. Importantly, st-LTP and st-LTD were significantly larger than LTP and LTD obtained by modulating the frequency and duration of mossy fiber bursts, probably because STDP expression involved postsynaptic in addition to presynaptic mechanisms. These results thus show that a Hebbian form of STDP occurs at the cerebellum input stage providing the substrate for phase-dependent binding of mossy fiber spikes to repetitive theta-frequency cycles of granule cell activity.SIGNIFICANCE STATEMENTLong-term synaptic plasticity is a fundamental property of the brain causing persistent modifications of neuronal communication thought to provide the cellular basis of learning and memory. The cerebellum is critical for learning the appropriate timing of sensorimotor behaviors but whether and how appropriate

  7. ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

    PubMed Central

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-01-01

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis. PMID:27649160

  8. Concept of relative variability of cardiac action potential duration and its test under various experimental conditions.

    PubMed

    Magyar, János; Kistamás, Kornél; Váczi, Krisztina; Hegyi, Bence; Horváth, Balázs; Bányász, Tamás; Nánási, Péter P; Szentandrássy, Norbert

    2016-01-01

    Beat-to-beat variability of action potential duration (short-term variability, SV) is an intrinsic property of mammalian myocardium. Since the majority of agents and interventions affecting SV may modify also action potential duration (APD), we propose here the concept of relative SV (RSV), where changes in SV are normalized to changes in APD and these data are compared to the control SV-APD relationship obtained by lengthening or shortening of action potentials by inward and outward current injections. Based on this concept the influence of the several experimental conditions like stimulation frequency, temperature, pH, redox-state and osmolarity were examined on RSV in canine ventricular myocytes using sharp microelectrodes. RSV was increased by high stimulation frequency (cycle lengths <0.7 s), high temperature (above 37ºC), oxidative agents (H2O2), while it was decreased by reductive environment. RSV was not affected by changes in pH (within the range of 6.4-8.4) and osmolarity of the solution (between 250-350 mOsm). The results indicate that changes in beat-to-beat variability of APD must be evaluated exclusively in terms of RSV; furthermore, some experimental conditions, including the stimulation frequency, redox-state and temperature have to be controlled strictly when analyzing alterations in the short-term variability of APD.

  9. TASK-1 Channels May Modulate Action Potential Duration of Human Atrial Cardiomyocytes

    PubMed Central

    Limberg, Sven H.; Netter, Michael F.; Rolfes, Caroline; Rinné, Susanne; Schlichthörl, Günter; Zuzarte, Marylou; Vassiliou, Timon; Moosdorf, Rainer; Wulf, Hinnerk; Daut, Jürgen; Sachse, Frank B.; Decher, Niels

    2011-01-01

    Background/Aims: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current ITASK-1. Methods and Results: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (ITASK-1) in human atrial tissue. We show that ITASK-1 contributes to the sustained outward current IKsus and that ITASK-1 is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of ITASK-1 can alter human atrial action potential duration. Conclusion: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation. PMID:22178873

  10. Spike-Dependent Intrinsic Plasticity Increases Firing Probability in Rat Striatal Neurons In Vivo

    PubMed Central

    Mahon, Séverine; Casassus, Guillaume; Mulle, Christophe; Charpier, Stéphane

    2003-01-01

    The collision of pre- and postynaptic activity is known to provide a trigger for controlling the gain of synaptic transmission between neurons. Here, using in vivo intracellular recordings of rat striatal output neurons, we analyse the effect of a single action potential, generated by ongoing synaptic activity, on subsequent excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the cerebral cortex. This pairing induced a short-term increase in the probability that cortically evoked EPSPs caused striatal cells to fire. This enhanced EPSP-spike coupling was associated with a decrease in the voltage firing threshold with no apparent change in the synaptic strength itself. Antidromic action potentials in striatal cells were also able to induce the facilitation while subthreshold EPSPs were ineffective, indicating that the postsynaptic spike was necessary and sufficient for the induction of the plasticity. A prior spontaneous action potential also enhanced the probability with which directly applied current pulses elicited firing, suggesting that the facilitation originated from changes in the intrinsic electrical properties of the postsynaptic cell. Using whole-cell recordings in cortico-striatal slices, we found that the increase in membrane excitability as well as in EPSP-spike coupling was abolished by low concentration of 4-aminopyridine. This suggests that the intrinsic plasticity results from a time-dependent modulation of a striatal voltage-dependent potassium current available close to the firing threshold. Action potentials thus provide a postsynaptic signal, not only for associative synaptic plasticity but also for activity-dependent intrinsic plasticity, which directly controls the efficacy of coupling between pre- and postsynaptic neurons. PMID:12844508

  11. Lyondell outage spikes prices

    SciTech Connect

    1996-08-07

    Methanol spot markets in the US Gulf Coast cooled a bit late last week from their Monday spike in the wake of a pipeline rupture and fire that shut down Lyondell Petrochemical`s Channelview, TX complex and its 248-million gal/year methanol plant. The unit resumed production last week and was expected to return to full service by August 3. Offering prices shot up at least 10% over the pre-accident level of about 50 cts/gal fob. No actual business could be confirmed at a price of more than 52 cts-53 cts/gal, however.

  12. [The effect of modulators of SK channels on simple spike firing frequency in the discharge of the cerebellar Purkinje cells in laboratory mice].

    PubMed

    Egorova, P A; Karelina, T V; Vlasova, O L; Antonov, S M; Besprozvanny, I B

    2014-01-01

    The effect of CyPPA, a positive modulator of small conductance calcium-activated potassium channels of type 3 and 2 (SK3/SK2), and of NS309, an activator of intermediate and small conductance calcium-activated potassium channels (IK/SK), on the activity of cerebellar Purkinje cells was studied in 2-month-old male mice. The use of 1 mM of CyPPA has led to a decrease of simple spike firing frequency in the discharge of Purkinje cells by 25%, on average, during 1 h after application. At the same time, application of 100 μM of NS309 has promoted a decrease in simple spike firing frequency by 47 %, on average, during 1 h after the beginning of the action. The obtained results confirm the hypothesis that SK channels participate in regulation of simple spike firing frequency in the discharge of Purkinje cells and are responsible for restriction of signal frequency. The effect of NS309 on simple spike firing frequency was more pronounced; therefore, the IK/SK channels may be suggested to play the cardinal role in regulation of spike activity of Purkinje cells. Since increasing simple spike frequency in the discharge of Purkinje cells is observed at many disturbances of motor activity, in particular, at spinocerebellar ataxia, it can be suggested that the studied compounds or substances of similar action are of interest as potential medicinal agents.

  13. 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.

  14. T-type calcium channels consolidate tonic action potential output of thalamic neurons to neocortex.

    PubMed

    Deleuze, Charlotte; David, François; Béhuret, Sébastien; Sadoc, Gérard; Shin, Hee-Sup; Uebele, Victor N; Renger, John J; Lambert, Régis C; Leresche, Nathalie; Bal, Thierry

    2012-08-29

    The thalamic output during different behavioral states is strictly controlled by the firing modes of thalamocortical neurons. During sleep, their hyperpolarized membrane potential allows activation of the T-type calcium channels, promoting rhythmic high-frequency burst firing that reduces sensory information transfer. In contrast, in the waking state thalamic neurons mostly exhibit action potentials at low frequency (i.e., tonic firing), enabling the reliable transfer of incoming sensory inputs to cortex. Because of their nearly complete inactivation at the depolarized potentials that are experienced during the wake state, T-channels are not believed to modulate tonic action potential discharges. Here, we demonstrate using mice brain slices that activation of T-channels in thalamocortical neurons maintained in the depolarized/wake-like state is critical for the reliable expression of tonic firing, securing their excitability over changes in membrane potential that occur in the depolarized state. Our results establish a novel mechanism for the integration of sensory information by thalamocortical neurons and point to an unexpected role for T-channels in the early stage of information processing.

  15. Effect of sodium perturbations on rat chemoreceptor spike generation: implications for a Poisson model

    PubMed Central

    Donnelly, David F; Panisello, Jose M; Boggs, Dona

    1998-01-01

    The sensitivity of arterial chemoreceptor spike generation to reductions in excitability was examined using rat chemoreceptors in vitro. Axonal excitability was reduced by reducing extracellular sodium concentration ([Na+]o) by 10-40 % or by applying low doses of tetrodotoxin (TTX).In normoxia and in hypoxia, an isosmotic reduction in [Na+]o caused a proportional decrease in single-fibre, spiking nerve activity. For a 20 % reduction in [Na+]o, nerve activity decreased to 54 ± 7 % of control in normoxia and 41 ± 5 % in hypoxia.Low doses of TTX (25-50 nM) caused a similar decrease in spiking frequency, but this response was variable amongst fibres, with some fibres unaffected by TTX.A reduction in [Na+]o by 20 % caused a slowing of conduction velocity, measured using an electrical stimulus delivered to an electrode placed in the carotid body. Threshold current for spike generation was increased by about 2·7 ± 1·4 %. Threshold current increased by 6·5 ± 3·7 % following a 40 % reduction in [Na+]o.The spike generation process was modelled as a Poisson process in which depolarizing events summate and give rise to an action potential. The experimental data were best fitted to a high order process characterized by a large number of events and high event threshold.This result is not consistent with depolarization events caused by episodic transmitter release, but suggests that afferent spike generation is an endogenous process in the afferent nerve fibres, perhaps linked to random channel activity or to thermal noise fluctuations. PMID:9679183

  16. Reading Between the Spikes: Real-Time Signal Processing in Neural Systems

    NASA Astrophysics Data System (ADS)

    Warland, David Karsten

    This thesis discusses biological strategies for real-time signal processing in neural systems. Nearly all creatures encode information about the world as patterns of identically shaped action potentials, or "spikes". As a result, all the animal's knowledge of the world is contained in the occurrence times of these discrete events. Traditional approaches to the study of neural coding emphasize the encoding process, resulting in predictions of average neural responses to a limited class of stimuli. However, these studies fail to address the relevant biological question: What can the organism "learn" about the outside world from real-time observations of its own spike trains? Therefore, this thesis approaches neural coding from the point of view of the organism itself: We learn to decode neural spike trains to obtain real-time estimates of sensory stimuli. In particular, this ability to extract continuous signals from spiking cells, together with the definition of an equivalent spectral noise level for a spiking neuron allows characterization of the information contained in patterns of neural response as well as forming the basis for the prediction of optimal neural computation strategies with spike trains. These methods are applied to the design and analysis of experiments on a single wide field, movement -sensitive neuron (H1) in the visual system of the blowfly Calliphora erythrocephela and to the filiform hair receptors of the wind-sensing system of the cricket Acheta domestica. This thesis also discusses the generalization of these strategies to collections of neurons and the applications to future work in the context of neural computation in the retina.

  17. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    PubMed

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca(2+)] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca(2+)-dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca(2+)-dependent phosphatase, calcineurin. Intracellular [Ca(2+)] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca(2)(+)]i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca(2+)]i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca(2+)-independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca(2+)]i. PP2A had no role. Conduction velocity was reduced by raised [Ca(2+)]i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca(2+)] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  18. ACTION-SPACE CLUSTERING OF TIDAL STREAMS TO INFER THE GALACTIC POTENTIAL

    SciTech Connect

    Sanderson, Robyn E.; Helmi, Amina; Hogg, David W.

    2015-03-10

    We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires three-dimensional positions and velocities for all stars to be fit, but does not require identification of any specific stream or determination of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered when the potential used to calculate the actions is closest to the true potential. Clustering is quantified with the Kullback-Leibler Divergence (KLD), which also provides conditional uncertainties for our parameter estimates. We show, for toy Gaia-like data in a spherical isochrone potential, that maximizing the KLD of the action distribution relative to a smoother distribution recovers the input potential. The precision depends on the observational errors and number of streams; using K III giants as tracers, we measure the enclosed mass at the average radius of the sample stars accurate to 3% and precise to 20%-40%. Recovery of the scale radius is precise to 25%, biased 50% high by the small galactocentric distance range of stars in our mock sample (1-25 kpc, or about three scale radii, with mean 6.5 kpc). 20-25 streams with at least 100 stars each are required for a stable confidence interval. With radial velocities (RVs) to 100 kpc, all parameters are determined with ∼10% accuracy and 20% precision (1.3% accuracy for the enclosed mass), underlining the need to complete the RV catalog for faint halo stars observed by Gaia.

  19. Radioxenon spiked air

    DOE PAGES

    Watrous, Matthew G.; Delmore, James E.; Hague, Robert K.; ...

    2015-08-27

    Four of the radioactive xenon isotopes (131mXe, 133mXe, 133Xe and 135Xe) with half-lives ranging from 9 h to 12 days are produced from nuclear fission and can be detected from days to weeks following their production and release. Being inert gases, they are readily transported through the atmosphere. Sources for release of radioactive xenon isotopes include operating nuclear reactors via leaks in fuel rods, medical isotope production facilities, and nuclear weapons' detonations. They are not normally released from fuel reprocessing due to the short half-lives. The Comprehensive Nuclear-Test-Ban Treaty has led to creation of the International Monitoring System. The Internationalmore » Monitoring System, when fully implemented, will consist of one component with 40 stations monitoring radioactive xenon around the globe. Monitoring these radioactive xenon isotopes is important to the Comprehensive Nuclear-Test-Ban Treaty in determining whether a seismically detected event is or is not a nuclear detonation. A variety of radioactive xenon quality control check standards, quantitatively spiked into various gas matrices, could be used to demonstrate that these stations are operating on the same basis in order to bolster defensibility of data across the International Monitoring System. This study focuses on Idaho National Laboratory's capability to produce three of the xenon isotopes in pure form and the use of the four xenon isotopes in various combinations to produce radioactive xenon spiked air samples that could be subsequently distributed to participating facilities.« less

  20. Environmental Asthma Reduction Potential Estimates for Selected Mitigation Actions in Finland Using a Life Table Approach

    PubMed Central

    Rumrich, Isabell Katharina; Hänninen, Otto

    2015-01-01

    Aims: To quantify the reduction potential of asthma in Finland achievable by adjusting exposures to selected environmental factors. Methods: A life table model for the Finnish population for 1986–2040 was developed and Years Lived with Disability caused by asthma and attributable to the following selected exposures were estimated: tobacco smoke (smoking and second hand tobacco smoke), ambient fine particles, indoor dampness and mould, and pets. Results: At baseline (2011) about 25% of the total asthma burden was attributable to the selected exposures. Banning tobacco was the most efficient mitigation action, leading to 6% reduction of the asthma burden. A 50% reduction in exposure to dampness and mould as well as a doubling in exposure to pets lead each to a 2% reduction. Ban of urban small scale wood combustion, chosen as a mitigation action to reduce exposure to fine particles, leads to a reduction of less than 1% of the total asthma burden. Combination of the most efficient mitigation actions reduces the total asthma burden by 10%. A more feasible combination of mitigation actions leads to 6% reduction of the asthma burden. Conclusions: The adjustment of environmental exposures can reduce the asthma burden in Finland by up to 10%. PMID:26067987

  1. Effects of visual stimulation on LFPs, spikes, and LFP-spike relations in PRR.

    PubMed

    Hwang, Eun Jung; Andersen, Richard A

    2011-04-01

    Local field potentials (LFPs) have shown diverse relations to the spikes across different brain areas and stimulus features, suggesting that LFP-spike relationships are highly specific to the underlying connectivity of a local network. If so, the LFP-spike relationship may vary even within one brain area under the same task condition if neurons have heterogeneous connectivity with the active input sources during the task. Here, we tested this hypothesis in the parietal reach region (PRR), which includes two distinct classes of motor goal planning neurons with different connectivity to the visual input, i.e., visuomotor neurons receive stronger visual input than motor neurons. We predicted that the visual stimulation would render both the spike response and the LFP-spike relationship different between the two neuronal subpopulations. Thus we examined how visual stimulations affect spikes, LFPs, and LFP-spike relationships in PRR by comparing their planning (delay) period activity between two conditions: with or without a visual stimulus at the reach target. Neurons were classified as visuomotor if the visual stimulation increased their firing rate, or as motor otherwise. We found that the visual stimulation increased LFP power in gamma bands >40 Hz for both classes. Moreover, confirming our prediction, the correlation between the LFP gamma power and the firing rate became higher for the visuomotor than motor neurons in the presence of visual stimulation. We conclude that LFPs vary with the stimulation condition and that the LFP-spike relationship depends on a given neuron's connectivity to the dominant input sources in a particular stimulation condition.

  2. Potentiation of antimalarial drug action by chlorpheniramine against multidrug-resistant Plasmodium falciparum in vitro.

    PubMed

    Nakornchai, Sunan; Konthiang, Phattanapong

    2006-09-01

    Chlorpheniramine, a histamine H1 receptor antagonist, was assayed for in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum K1 strain and chloroquine-resistant P. falciparum T9/94 clone, by measuring the 3H-hypoxanthine incorporation. Chlorphenirame inhibited P. falciparum K1 and T9/94 growth with IC50 values of 136.0+/-40.2 microM and 102.0+/-22.6 microM respectively. A combination of antimalarial drug and chlorpheniramine was tested against resistant P. falciparum in vitro. Isobologram analysis showed that chlorpheniramine exerts marked synergistic action on chloroquine against P. falciparum K1 and T9/94. Chlorpheniramine also potentiated antimalarial action of mefloquine, quinine or pyronaridine against both of the resistant strains of P. falciparum. However, chlorpheniramine antagonism with artesunate was obtained in both P. falciparum K1 and T9/94. The results in this study indicate that antihistaminic drugs may be promising candidates for potentiating antimalarial drug action against drug resistant malarial parasites.

  3. The real-time link between person perception and action: brain potential evidence for dynamic continuity.

    PubMed

    Freeman, Jonathan B; Ambady, Nalini; Midgley, Katherine J; Holcomb, Phillip J

    2011-01-01

    Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw.

  4. The real-time link between person perception and action: Brain potential evidence for dynamic continuity

    PubMed Central

    Freeman, Jonathan B.; Ambady, Nalini; Midgley, Katherine J.; Holcomb, Phillip J.

    2010-01-01

    Using event-related potentials, we investigated how the brain extracts information from another’s face and translates it into relevant action in real-time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250-550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential (LRP) revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target’s sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another’s face before perceivers have finished interpreting what they just saw. PMID:20602284

  5. A novel anionic conductance affects action potential duration in isolated rat ventricular myocytes.

    PubMed

    Spencer, C I; Uchida, W; Kozlowski, R Z

    2000-01-01

    Effects of extracellular anions were studied in electrophysiological experiments on freshly isolated rat ventricular myocytes. Under current-clamp, action potential duration (APD) was prolonged by reducing the extracellular Cl(-) concentration and shortened by replacement of extracellular Cl(-) with I(-). Under voltage-clamp, membrane potential steps or ramps evoked an anionic background current (I(AB)) carried by either Cl(-), Br(-), I(-) or NO(3)(-). Activation of I(AB) was Ca(2+)- and cyclic AMP-independent, and was unaffected by cell shrinkage. I(AB) was insensitive to stilbene and fenamate anion transport blockers at concentrations that inhibit Ca(2+)-, cyclic AMP- and swelling-activated Cl(-) currents in ventricular cells of other mammals. These results suggest that I(AB) may be carried by a novel class of Cl(-) channel. Correlation of anion substitution experiments on membrane current and action potentials revealed that I(AB) could play a major role in controlling rat ventricular APD. These findings have important implications for those studying cardiac Cl(-) channels as potential targets for novel antiarrythmic agents.

  6. Constraining the Galactic potential via action-based distribution functions for mono-abundance stellar populations

    NASA Astrophysics Data System (ADS)

    Ting, Yuan-Sen; Rix, Hans-Walter; Bovy, Jo; van de Ven, Glenn

    2013-09-01

    We present a rigorous and practical way of constraining the Galactic potential based on the phase-space information for many individual stars. Such an approach is needed to dynamically model the data from ongoing spectroscopic surveys of the Galaxy and in the future Gaia. This approach describes the orbit distribution of stars by a family of parametrized distribution function (DF) proposed by McMillan and Binney, which are based on actions. We find that these parametrized DFs are flexible enough to capture well the observed phase-space distributions of individual abundance-selected Galactic subpopulations of stars (`mono-abundance populations') for a disc-like gravitational potential, which enables independent dynamical constraints from each of the Galactic mono-abundance populations. We lay out a statistically rigorous way to constrain the Galactic potential parameters by constructing the joint likelihood of potential and DF parameters, and subsequently marginalizing over the DF parameters. This approach explicitly incorporates the spatial selection function inherent to all Galactic surveys, and can account for the uncertainties of the individual position-velocity observations. On that basis, we study the precision of the parameters of the Galactic potential that can be reached with various sample sizes and realistic spatial selection functions. By creating mock samples from the DF, we show that, even under a restrictive and realistic spatial selection function, given a two-parameter gravitational potential, one can recover the true potential parameters to a few per cent with sample sizes of a few thousands. The assumptions of axisymmetry, of DFs that are smooth in the actions and of no time variation remain important limitations in our current study.

  7. Effects of rosiglitazone on the configuration of action potentials and ion currents in canine ventricular cells

    PubMed Central

    Szentandrássy, N; Harmati, G; Bárándi, L; Simkó, J; Horváth, B; Magyar, J; Bányász, T; Lőrincz, I; Szebeni, A; Kecskeméti, V; Nánási, PP

    2011-01-01

    BACKGROUND AND PURPOSE In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts. EXPERIMENTAL APPROACH Standard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts. KEY RESULTS At concentrations ≥10 µM rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects developed rapidly and were readily reversible upon washout. Rosiglitazone suppressed several transmembrane ion currents, concentration-dependently, under conventional voltage clamp conditions and altered their kinetic properties. The EC50 value for this inhibition was 25.2 ± 2.7 µM for the transient outward K+ current (Ito), 72.3 ± 9.3 µM for the rapid delayed rectifier K+ current (IKr) and 82.5 ± 9.4 µM for the L-type Ca2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K+ current (IK1) was not affected by rosiglitazone up to concentrations of 100 µM. Suppression of Ito, IKr, and ICa was confirmed also under action potential voltage clamp conditions. CONCLUSIONS AND IMPLICATIONS Alterations in the densities and kinetic properties of ion currents may carry serious pro-arrhythmic risk in case of overdose with rosiglitazone, especially in patients having multiple cardiovascular risk factors, like elderly diabetic patients. LINKED ARTICLE This article is commented on by Hancox, pp. 496–498 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01281.x PMID:21232044

  8. FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels.

    PubMed

    Deng, Pan-Yue; Rotman, Ziv; Blundon, Jay A; Cho, Yongcheol; Cui, Jianmin; Cavalli, Valeria; Zakharenko, Stanislav S; Klyachko, Vitaly A

    2013-02-20

    Loss of FMRP causes fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx, and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation independent and are mediated selectively by BK channels via interaction of FMRP with BK channel's regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology.

  9. Excitatory amino acids acting on metabotropic glutamate receptors broaden the action potential in hippocampal neurons.

    PubMed

    Hu, G Y; Storm, J F

    1991-12-24

    Activation of metabotropic glutamate receptors (mGluRs, QP or ACPD receptors) has recently been shown to cause depolarization, blockade of the slow after-hyperpolarization and depression of calcium currents in hippocampal pyramidal cells. Here, we report evidence for a new mGluR-mediated effect: slowing of the spike repolarization in CA1 cells in rat hippocampal slices. During blockade of the ionotropic glutamate receptors, the mGluR agonists trans-1-amino-cyclopentyl-1,3-dicarboxylate (t-ACPD), quisqualate or L-glutamate caused spike broadening. In contrast, the ionotropic receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) was ineffective. The spike broadening may act in concert with the other mGluR effects, e.g. by further increasing the influx of Ca2+ ions which, in turn, may contribute to synaptic modulation.

  10. Rayleigh--Taylor spike evaporation

    SciTech Connect

    Schappert, G. T.; Batha, S. H.; Klare, K. A.; Hollowell, D. E.; Mason, R. J.

    2001-09-01

    Laser-based experiments have shown that Rayleigh--Taylor (RT) growth in thin, perturbed copper foils leads to a phase dominated by narrow spikes between thin bubbles. These experiments were well modeled and diagnosed until this '' spike'' phase, but not into this spike phase. Experiments were designed, modeled, and performed on the OMEGA laser [T. R. Boehly, D. L. Brown, R. S. Craxton , Opt. Commun. 133, 495 (1997)] to study the late-time spike phase. To simulate the conditions and evolution of late time RT, a copper target was fabricated consisting of a series of thin ridges (spikes in cross section) 150 {mu}m apart on a thin flat copper backing. The target was placed on the side of a scale-1.2 hohlraum with the ridges pointing into the hohlraum, which was heated to 190 eV. Side-on radiography imaged the evolution of the ridges and flat copper backing into the typical RT bubble and spike structure including the '' mushroom-like feet'' on the tips of the spikes. RAGE computer models [R. M. Baltrusaitis, M. L. Gittings, R. P. Weaver, R. F. Benjamin, and J. M. Budzinski, Phys. Fluids 8, 2471 (1996)] show the formation of the '' mushrooms,'' as well as how the backing material converges to lengthen the spike. The computer predictions of evolving spike and bubble lengths match measurements fairly well for the thicker backing targets but not for the thinner backings.

  11. Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala.

    PubMed

    Faber, E S Louise; Sah, Pankaj

    2003-10-15

    In many neurons, trains of action potentials show frequency-dependent broadening. This broadening results from the voltage-dependent inactivation of K+ currents that contribute to action potential repolarisation. In different neuronal cell types these K+ currents have been shown to be either slowly inactivating delayed rectifier type currents or rapidly inactivating A-type voltage-gated K+ currents. Recent findings show that inactivation of a Ca2+-dependent K+ current, mediated by large conductance BK-type channels, also contributes to spike broadening. Here, using whole-cell recordings in acute slices, we examine spike broadening in lateral amygdala projection neurons. Spike broadening is frequency dependent and is reversed by brief hyperpolarisations. This broadening is reduced by blockade of voltage-gated Ca2+ channels and BK channels. In contrast, broadening is not blocked by high concentrations of 4-aminopyridine (4-AP) or alpha-dendrotoxin. We conclude that while inactivation of BK-type Ca2+-activated K+ channels contributes to spike broadening in lateral amygdala neurons, inactivation of another as yet unidentified outward current also plays a role.

  12. A unified description of cerebellar inter-spike interval distributions and variabilities using summation of Gaussians.

    PubMed

    Chen, Yanqing; Nitz, Douglas A

    2011-01-01

    Neuronal inter-spike intervals (ISIs) have previously been described as Poisson, Gamma, inverse Gaussian or other unimodal distributions. We analyzed ISIs of rhythmic and arrhythmic neuronal spike trains in cerebellum recorded from freely behaving rats, and found that their distributions can be described as the summation or integration of multiple Gaussian distributions. The ISIs of rhythmic cerebellar Purkinje cells have a main Gaussian peak at a basic firing interval and exponentially reduced peaks at multiples of this firing period. ISIs of arrhythmic Purkinje cells can be modeled as the integration of multiple Gaussian distributions centered at continuous intervals with exponentially reduced peak amplitudes. The sources of variability are directly related to the relative timing of action potentials between neighboring cells since we show that irregularities of discharge in one cell are associated with the previous history of its discharge in time relative to another cell. Through relative phase analyses, we demonstrate that the shape and the mathematical form of the ISI distributions in cerebellum are direct result of dynamic interactions in the nearby neuronal network, in addition to intrinsic firing properties. The analysis in this paper provides a unified description of cerebellar inter-spike interval distributions which deviate from the usual Poisson assumptions. Our results suggest the existence of an intrinsic rhythmicity in cells exhibiting arrhythmic spike trains in cerebellum, and may identify an important source of variability in neuronal firing patterns that is relevant to the mechanism of neural computation in cerebellum.

  13. Activity-dependent plasticity of spike pauses in cerebellar Purkinje cells

    PubMed Central

    Grasselli, Giorgio; He, Qionger; Wan, Vivian; Adelman, John P.; Ohtsuki, Gen; Hansel, Christian

    2016-01-01

    Summary Plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst–pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice) and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning. PMID:26972012

  14. Regional differences in action potential characteristics and membrane currents of guinea-pig left ventricular myocytes.

    PubMed

    Main, M C; Bryant, S M; Hart, G

    1998-11-01

    Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA). Mean action potential duration at 90 % repolarization (APD90) was 237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial (n = 30) and 204 +/- 7 ms in subepicardial myocytes (n = 36). L-type calcium current (ICa) density and background potassium current (IK1) density were similar in the three regions studied. Delayed rectifier current (IK) was measured as deactivating tail current, elicited on repolarization back to -45 mV after 2 s step depolarizations to test potentials ranging from -10 to +80 mV. Mean IK density (after a step to +80 mV) was larger in subepicardial myocytes (1.59 +/- 0.16 pA pF-1, n = 16) than in either subendocardial (1.16 +/- 0.12 pA pF-1, n = 17) or midmyocardial (1. 13 +/- 0.11 pA pF-1, n = 21) myocytes (P < 0.05, ANOVA). The La3+-insensitive current (IKs) elicited on repolarization back to -45 mV after a 250 ms step depolarization to +60 mV was similar in the three regions studied. The La3+-sensitive tail current, (IKr) was greater in subepicardial (0.50 +/- 0.04 pA pF-1, n = 11) than in subendocardial (0.25 +/- 0.05 pA pF-1, n = 9) or in midmyocardial myocytes (0.38 +/- 0.05 pA pF-1, n = 11, P < 0.05, ANOVA). The contribution of a Na+ background current to regional differences in APD was assessed by application of 0.1 microM tetrodotoxin (TTX). TTX-induced shortening of APD90 was greater in subendocardial myocytes (35.7 +/- 7.1 %, n = 11) than in midmyocardial (15.7 +/- 3. 8 %, n = 10) and subepicardial (20.2 +/- 4.3 %, n = 11) myocytes (P < 0.05, ANOVA). Regional differences in action potential characteristics between subendocardial, midmyocardial, and subepicardial myocytes isolated from

  15. Dendritic Synapse Location and Neocortical Spike-Timing-Dependent Plasticity

    PubMed Central

    Froemke, Robert C.; Letzkus, Johannes J.; Kampa, Björn M.; Hang, Giao B.; Stuart, Greg J.

    2010-01-01

    While it has been appreciated for decades that synapse location in the dendritic tree has a powerful influence on signal processing in neurons, the role of dendritic synapse location on the induction of long-term synaptic plasticity has only recently been explored. Here, we review recent work revealing how learning rules for spike-timing-dependent plasticity (STDP) in cortical neurons vary with the spatial location of synaptic input. A common principle appears to be that proximal synapses show conventional STDP, whereas distal inputs undergo plasticity according to novel learning rules. One crucial factor determining location-dependent STDP is the backpropagating action potential, which tends to decrease in amplitude and increase in width as it propagates into the dendritic tree of cortical neurons. We discuss additional location-dependent mechanisms as well as the functional implications of heterogeneous learning rules at different dendritic locations for the organization of synaptic inputs. PMID:21423515

  16. Firing regulation of fast-spiking interneurons by autaptic inhibition

    NASA Astrophysics Data System (ADS)

    Guo, Daqing; Chen, Mingming; Perc, Matjaž; Wu, Shengdun; Xia, Chuan; Zhang, Yangsong; Xu, Peng; Xia, Yang; Yao, Dezhong

    2016-05-01

    Fast-spiking (FS) interneurons in the brain are self-innervated by powerful inhibitory GABAergic autaptic connections. By computational modelling, we investigate how autaptic inhibition regulates the firing response of such interneurons. Our results indicate that autaptic inhibition both boosts the current threshold for action potential generation and modulates the input-output gain of FS interneurons. The autaptic transmission delay is identified as a key parameter that controls the firing patterns and determines multistability regions of FS interneurons. Furthermore, we observe that neuronal noise influences the firing regulation of FS interneurons by autaptic inhibition and extends their dynamic range for encoding inputs. Importantly, autaptic inhibition modulates noise-induced irregular firing of FS interneurons, such that coherent firing appears at an optimal autaptic inhibition level. Our results reveal the functional roles of autaptic inhibition in taming the firing dynamics of FS interneurons.

  17. Radioxenon spiked air

    SciTech Connect

    Watrous, Matthew G.; Delmore, James E.; Hague, Robert K.; Houghton, Tracy P.; Jenson, Douglas D.; Mann, Nick R.

    2015-08-27

    Four of the radioactive xenon isotopes (131mXe, 133mXe, 133Xe and 135Xe) with half-lives ranging from 9 h to 12 days are produced from nuclear fission and can be detected from days to weeks following their production and release. Being inert gases, they are readily transported through the atmosphere. Sources for release of radioactive xenon isotopes include operating nuclear reactors via leaks in fuel rods, medical isotope production facilities, and nuclear weapons' detonations. They are not normally released from fuel reprocessing due to the short half-lives. The Comprehensive Nuclear-Test-Ban Treaty has led to creation of the International Monitoring System. The International Monitoring System, when fully implemented, will consist of one component with 40 stations monitoring radioactive xenon around the globe. Monitoring these radioactive xenon isotopes is important to the Comprehensive Nuclear-Test-Ban Treaty in determining whether a seismically detected event is or is not a nuclear detonation. A variety of radioactive xenon quality control check standards, quantitatively spiked into various gas matrices, could be used to demonstrate that these stations are operating on the same basis in order to bolster defensibility of data across the International Monitoring System. This study focuses on Idaho National Laboratory's capability to produce three of the xenon isotopes in pure form and the use of the four xenon isotopes in various combinations to produce radioactive xenon spiked air samples that could be subsequently distributed to participating facilities.

  18. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    PubMed Central

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-01-01

    Very fine needle-electrode arrays potentially offer both low invasiveness and high spatial resolution of electrophysiological neuronal recordings in vivo. Herein we report the penetrating and recording capabilities of silicon-growth-based three-dimensional microscale-diameter needle-electrodes arrays. The fabricated needles exhibit a circular-cone shape with a 3-μm-diameter tip and a 210-μm length. Due to the microscale diameter, our silicon needles are more flexible than other microfabricated silicon needles with larger diameters. Coating the microscale-needle-tip with platinum black results in an impedance of ~600 kΩ in saline with output/input signal amplitude ratios of more than 90% at 40 Hz–10 kHz. The needles can penetrate into the whisker barrel area of a rat's cerebral cortex, and the action potentials recorded from some neurons exhibit peak-to-peak amplitudes of ~300 μVpp. These results demonstrate the feasibility of in vivo neuronal action potential recordings with a microscale needle-electrode array fabricated using silicon growth technology. PMID:24785307

  19. Stretch-induced excitation and action potential changes of single cardiac cells.

    PubMed

    Riemer, Tara L; Tung, Leslie

    2003-01-01

    Mechanoelectric coupling (MEC) has been studied extensively in the heart at the tissue and organ levels, but to only a limited extent in single cells because of the technical challenges. New results are presented in which MEC was studied in 57 single frog ventricular myocytes that were held on both ends by glass holding pipettes. Axial stretch was applied either by displacement of the pipettes, or by a glass fiber around which the cell was wrapped, that was displaced in a pulsatile or sinusoidal fashion. Electrical activity of the cell was monitored either by active contraction, by intracellular action potentials, or by focal extracellular potentials. Of more than 350 stretches applied to 57 cells with amplitudes ranging from 3% to 35%, only 4 cases of mechanically induced stimulation were observed. In 252 stretches applied to 32 cells in which action potential duration (APD) was measured, no change >20% was observed, except in 3 cells in which APD increased by >100%, and in 2 cells with extended triggered activity. Thus, in contrast to studies in intact tissue, single frog ventricular myocytes are generally insensitive to direct axial stretch. However, robust mechanosensitive responses were observed in 7 of 57 ( approximately 12%) cells. The results of other single cell studies are reviewed, and the significance of differences in tissue-level and single cell results is discussed.

  20. Effects of bath resistance on action potentials in the squid giant axon: myocardial implications.

    PubMed Central

    Wu, J; Wikswo, J P

    1997-01-01

    This study presents a simplified version of the quasi-one-dimensional theory (Wu, J., E. A. Johnson, and J. M. Kootsey. 1996. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys. J. 71:2427-2439) with two components of the extracellular current, along and perpendicular to the axis, and a simulation and its experimental confirmation for the giant axon of the squid. By extending the one-dimensional core conductor cable equations, this theory predicts, as confirmed by the experiment, that the shapes of the intracellular and the extracellular action potentials are related to the resistance of the bath. Such a result was previously only expected by the field theories. The correlation between the shapes of the intracellular and the extracellular potentials of the giant axon of the squid resembles that observed during the anisotropic propagation of excitation in cardiac muscle. Therefore, this study not only develops a quasi-one-dimensional theory for a squid axon, but also provides one possible factor contributing to the anisotropic propagation of action potentials in cardiac muscle. PMID:9370430

  1. An Excel-based implementation of the spectral method of action potential alternans analysis.

    PubMed

    Pearman, Charles M

    2014-12-01

    Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results.

  2. Carbon monoxide effects on human ventricle action potential assessed by mathematical simulations

    PubMed Central

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R.

    2013-01-01

    Carbon monoxide (CO) that is produced in a number of different mammalian tissues is now known to have significant effects on the cardiovascular system. These include: (i) vasodilation, (ii) changes in heart rate and strength of contractions, and (iii) modulation of autonomic nervous system input to both the primary pacemaker and the working myocardium. Excessive CO in the environment is toxic and can initiate or mediate life threatening cardiac rhythm disturbances. Recent reports link these ventricular arrhythmias to an increase in the slowly inactivating, or “late” component of the Na+ current in the mammalian heart. The main goal of this paper is to explore the basis of this pro-arrhythmic capability of CO by incorporating changes in CO-induced ion channel activity with intracellular signaling pathways in the mammalian heart. To do this, a quite well-documented mathematical model of the action potential and intracellular calcium transient in the human ventricular myocyte has been employed. In silico iterations based on this model provide a useful first step in illustrating the cellular electrophysiological consequences of CO that have been reported from mammalian heart experiments. Specifically, when the Grandi et al. model of the human ventricular action potential is utilized, and after the Na+ and Ca2+ currents in a single myocyte are modified based on the experimental literature, early after-depolarization (EAD) rhythm disturbances appear, and important elements of the underlying causes of these EADs are revealed/illustrated. Our modified mathematical model of the human ventricular action potential also provides a convenient digital platform for designing future experimental work and relating these changes in cellular cardiac electrophysiology to emerging clinical and epidemiological data on CO toxicity. PMID:24146650

  3. Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles

    PubMed Central

    Tucker, Kristal R.; Block, Ethan R.; Levitan, Edwin S.

    2015-01-01

    Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H+-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca2+-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP+), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H+ countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs. PMID:26216995

  4. Neuronal Competition for Action Potential Initiation Sites in a Circuit Controlling Simple Learning

    PubMed Central

    Cruz, Georgina E.; Sahley, Christie L.; Muller, Kenneth J.

    2007-01-01

    The spatial and temporal patterns of action potential initiations were studied in a behaving leech preparation to determine the basis of increased firing that accompanies sensitization, a form of non-associative learning requiring the S-interneurons. Little is known at the network level about mechanisms of behavioral sensitization. The S-interneurons, one in each ganglion and linked by electrical synapses with both neighbors to form a chain, are interposed between sensory and motor neurons. In sensitized preparations the strength of shortening is related to S-cell firing, which itself is the result of impulses initiating in several S-cells. Because the S-cells, as independent initiation sites, all contribute to activity in the chain, it was hypothesized that during sensitization, increased multi-site activity increased the chain's firing rate. However, it was found that during sensitization, the single site with the largest initiation rate, the S-cell in the stimulated segment, suppressed initiations in adjacent ganglia. Experiments showed this was both because (1) it received the earliest, greatest input and (2) the delayed synaptic input to the adjacent S-cells coincided with the action potential refractory period. A compartmental model of the S-cell and its inputs showed that a simple, intrinsic mechanism of inexcitability after each action potential may account for suppression of impulse initiations. Thus, a non-synaptic competition between neurons alters synaptic integration in the chain. In one mode, inputs to different sites sum independently, whereas in another, synaptic input to a single site precisely specifies the overall pattern of activity. PMID:17644266

  5. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation.

    PubMed

    Yue, L; Feng, J; Gaspo, R; Li, G R; Wang, Z; Nattel, S

    1997-10-01

    Rapid electrical activation, as occurs during atrial fibrillation (AF), is known to cause reductions in atrial refractoriness and in adaptation to heart rate of the atrial refractory period, which promote the maintenance of AF, but the underlying ionic mechanisms are unknown. In order to determine the cellular and ionic changes caused by chronic atrial tachycardia, we studied right atrial myocytes from dogs subjected to 1, 7, or 42 days of atrial pacing at 400/min and compared them with myocytes from sham-operated dogs (pacemaker inserted but not activated). Rapid pacing led to progressive increases in the duration of AF induced by bursts of 10-Hz stimuli (from 3 +/- 2 seconds in sham-operated dogs to 3060 +/- 707 seconds in dogs after 42 days of pacing, P < .001) and reduced atrial refractoriness and adaptation to rate of the atrial refractory period. Voltage-clamp studies showed that chronic rapid pacing did not alter inward rectifier K+ current, rapid or slow components of the delayed rectifier current, the ultrarapid delayed rectifier current, T-type Ca2+ current, or Ca(2+)-dependent Cl- current. In contrast, the densities of transient outward current (Ito) and L-type Ca2+ current (ICa) were progressively reduced as the duration of rapid pacing increased, without concomitant changes in kinetics or voltage dependence. In keeping with in vivo changes in refractoriness, action potential duration (APD) and APD adaptation to rate were decreased by rapid pacing. The response of the action potential and ionic currents flowing during the action potential (as exposed by action-potential voltage clamp) to nifedipine in normal canine cells and in cells from rapidly paced dogs suggested that the APD changes in paced dogs were largely due to reductions in ICa. We conclude that sustained atrial tachycardia reduces Ito and ICa, that the reduced ICa decreases APD and APD adaptation to rate, and that these cellular changes likely account for the alterations in atrial

  6. The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve.

    PubMed

    Li, Yongping; Lao, Jie; Zhao, Xin; Tian, Dong; Zhu, Yi; Wei, Xiaochun

    2014-01-15

    The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential.

  7. The Healthy Bus project in Denmark: need for an action potential assessment.

    PubMed

    Poulsen, Kjeld B

    2004-06-01

    Research over the last 50 years has repeatedly documented that bus drivers are exposed to several physical and psychological risk factors, which are associated with health problems in the form of heart, musculo-skeletal and stomach disease, and increased coronary mortality. So why has there been little action to improve the situation when it is so obviously indicated by such assessments? This article describes the long and complex process that has made it possible to launch almost 200 interventions among the 3500 municipal bus drivers in Copenhagen. Using a participative action research design, new evidence was gathered by broadening the traditional work environmental scope to lifestyle, health issues and private matters. Comparing this updated needs assessment with a national reference population, it was found that drivers were often still worse off. Again, simply presenting new evidence did not seem to lead to changes and further work is needed to empower the stakeholders so that they can commit to start making effective interventions. It is concluded that every needs assessment has to be supplemented with an evaluation of the action potential.

  8. The ionic mechanism of gamma resonance in rat striatal fast-spiking neurons.

    PubMed

    Sciamanna, Giuseppe; Wilson, Charles J

    2011-12-01

    Striatal fast-spiking (FS) cells in slices fire in the gamma frequency range and in vivo are often phase-locked to gamma oscillations in the field potential. We studied the firing patterns of these cells in slices from rats ages 16-23 days to determine the mechanism of their gamma resonance. The resonance of striatal FS cells was manifested as a minimum frequency for repetitive firing. At rheobase, cells fired a doublet of action potentials or doublets separated by pauses, with an instantaneous firing rate averaging 44 spikes/s. The minimum rate for sustained firing was also responsible for the stuttering firing pattern. Firing rate adapted during each episode of firing, and bursts were terminated when firing was reduced to the minimum sustainable rate. Resonance and stuttering continued after blockade of Kv3 current using tetraethylammonium (0.1-1 mM). Both gamma resonance and stuttering were strongly dependent on Kv1 current. Blockade of Kv1 channels with dendrotoxin-I (100 nM) completely abolished the stuttering firing pattern, greatly lowered the minimum firing rate, abolished gamma-band subthreshold oscillations, and slowed spike frequency adaptation. The loss of resonance could be accounted for by a reduction in potassium current near spike threshold and the emergence of a fixed spike threshold. Inactivation of the Kv1 channel combined with the minimum firing rate could account for the stuttering firing pattern. The resonant properties conferred by this channel were shown to be adequate to account for their phase-locking to gamma-frequency inputs as seen in vivo.

  9. Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

    PubMed

    Takagi, Hiroaki; Hashitani, Hikaru

    2016-10-15

    The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization.

  10. Model of spatio-temporal propagation of action potentials in the Schaffer collateral pathway of the CA1 area of the rat hippocampus.

    PubMed

    Bernard, C; Cannon, R C; Ben Ari, Y; Wheal, H V

    1997-01-01

    There is a sharp contrast between the profuse in vivo axonal arborization of CA3 pyramidal cells in the CA1 area and the low probability of finding pairs of connected CA3-CA1 pyramidal cells in vitro. These anatomical differences contribute to a connectivity argument for discrepancies between electrophysiological data recorded in vitro and in vivo. In order to investigate this issue, we have developed a realistic computer model of the Schaffer collateral pathway of the hippocampus and analyzed the spatio-temporal distribution of action potentials along this pathway following three different types of electrical test stimulus. Direct activation of mossy fibers, CA3 pyramidal cells and focal stimulation of CA1 stratum radiatum were investigated. The parameters of the model were selected from available biological data. Spikes in Schaffer collaterals were followed from their onset in the CA3 pyramidal cell initial segment to the last order branches of their axonal tree in two types of configuration: the whole hippocampus and the slice configuration. The anatomical and electropysiological characteristics of the mossy fibre and Schaffer collateral pathways were found to impose strong constraints on the spatio-temporal distribution of action potentials in the CA1 area. Specific projection zones are determined by the spatial localization of the emitting CA3 pyramidal cells. Their position also defines precise time windows during which some CA1 projection zones receive a large number of correlated signals. Moreover, the variability of the delay at the mossy fibre/CA3 pyramidal cell synapse seems to provide the CA1 projection zones with a background level of excitation. Finally, we show how the patterns of activation obtained in the whole hippocampus are different from those obtained in the slice.

  11. Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence Detection and Activity Propagation

    PubMed Central

    Chua, Yansong; Morrison, Abigail

    2016-01-01

    The role of dendritic spiking mechanisms in neural processing is so far poorly understood. To investigate the role of calcium spikes in the functional properties of the single neuron and recurrent networks, we investigated a three compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in the distal compartment. By performing single neuron simulations with noisy synaptic input and occasional large coincident input at either just the distal compartment or at both somatic and distal compartments, we show that the presence of calcium spikes confers a substantial advantage for coincidence detection in the former case and a lesser advantage in the latter. We further show that the experimentally observed critical frequency phenomenon, in which action potentials triggered by stimuli near the soma above a certain frequency trigger a calcium spike at distal dendrites, leading to further somatic depolarization, is not exhibited by a neuron receiving realistically noisy synaptic input, and so is unlikely to be a necessary component of coincidence detection. We next investigate the effect of calcium spikes in propagation of spiking activities in a feed-forward network (FFN) embedded in a balanced recurrent network. The excitatory neurons in the network are again connected to either just the distal, or both somatic and distal compartments. With purely distal connectivity, activity propagation is stable and distinguishable for a large range of recurrent synaptic strengths if the feed-forward connections are sufficiently strong, but propagation does not occur in the absence of calcium spikes. When connections are made to both the somatic and the distal compartments, activity propagation is achieved for neurons with active calcium dynamics at a much smaller number of neurons per pool, compared to a network of passive neurons, but quickly becomes unstable as the strength of recurrent synapses increases. Activity propagation at higher scaling factors can be

  12. Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence Detection and Activity Propagation.

    PubMed

    Chua, Yansong; Morrison, Abigail

    2016-01-01

    The role of dendritic spiking mechanisms in neural processing is so far poorly understood. To investigate the role of calcium spikes in the functional properties of the single neuron and recurrent networks, we investigated a three compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in the distal compartment. By performing single neuron simulations with noisy synaptic input and occasional large coincident input at either just the distal compartment or at both somatic and distal compartments, we show that the presence of calcium spikes confers a substantial advantage for coincidence detection in the former case and a lesser advantage in the latter. We further show that the experimentally observed critical frequency phenomenon, in which action potentials triggered by stimuli near the soma above a certain frequency trigger a calcium spike at distal dendrites, leading to further somatic depolarization, is not exhibited by a neuron receiving realistically noisy synaptic input, and so is unlikely to be a necessary component of coincidence detection. We next investigate the effect of calcium spikes in propagation of spiking activities in a feed-forward network (FFN) embedded in a balanced recurrent network. The excitatory neurons in the network are again connected to either just the distal, or both somatic and distal compartments. With purely distal connectivity, activity propagation is stable and distinguishable for a large range of recurrent synaptic strengths if the feed-forward connections are sufficiently strong, but propagation does not occur in the absence of calcium spikes. When connections are made to both the somatic and the distal compartments, activity propagation is achieved for neurons with active calcium dynamics at a much smaller number of neurons per pool, compared to a network of passive neurons, but quickly becomes unstable as the strength of recurrent synapses increases. Activity propagation at higher scaling factors can be

  13. Predictability of EEG interictal spikes.

    PubMed Central

    Scott, D A; Schiff, S J

    1995-01-01

    To determine whether EEG spikes are predictable, time series of EEG spike intervals were generated from subdural and depth electrode recordings from four patients. The intervals between EEG spikes were hand edited to ensure high accuracy and eliminate false positive and negative spikes. Spike rates (per minute) were generated from longer time series, but for these data hand editing was usually not feasible. Linear and nonlinear models were fit to both types of data. One patient had no linear or nonlinear predictability, two had predictability that could be well accounted for with a linear stochastic model, and one had a degree of nonlinear predictability for both interval and rate data that no linear model could adequately account for. PMID:8580318

  14. Gamma oscillations of spiking neural populations enhance signal discrimination.

    PubMed

    Masuda, Naoki; Doiron, Brent

    2007-11-01

    Selective attention is an important filter for complex environments where distractions compete with signals. Attention increases both the gamma-band power of cortical local field potentials and the spike-field coherence within the receptive field of an attended object. However, the mechanisms by which gamma-band activity enhances, if at all, the encoding of input signals are not well understood. We propose that gamma oscillations induce binomial-like spike-count statistics across noisy neural populations. Using simplified models of spiking neurons, we show how the discrimination of static signals based on the population spike-count response is improved with gamma induced binomial statistics. These results give an important mechanistic link between the neural correlates of attention and the discrimination tasks where attention is known to enhance performance. Further, they show how a rhythmicity of spike responses can enhance coding schemes that are not temporally sensitive.

  15. 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

  16. Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe.

    PubMed

    Jin, Lei; Han, Zhou; Platisa, Jelena; Wooltorton, Julian R A; Cohen, Lawrence B; Pieribone, Vincent A

    2012-09-06

    Monitoring neuronal electrical activity using fluorescent protein-based voltage sensors has been limited by small response magnitudes and slow kinetics of existing probes. Here we report the development of a fluorescent protein voltage sensor, named ArcLight, and derivative probes that exhibit large changes in fluorescence intensity in response to voltage changes. ArcLight consists of the voltage-sensing domain of Ciona intestinalis voltage-sensitive phosphatase and super ecliptic pHluorin that carries the point mutation A227D. The fluorescence intensity of ArcLight A242 decreases by 35% in response to a 100 mV depolarization when measured in HEK293 cells, which is more than five times larger than the signals from previously reported fluorescent protein voltage sensors. We show that the combination of signal size and response speed of these new probes allows the reliable detection of single action potentials and excitatory potentials in individual neurons and dendrites.

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

    NASA Astrophysics Data System (ADS)

    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.

  18. 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.

  19. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials.

    PubMed

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J

    2016-08-11

    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.

  20. 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.

  1. Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation.

    PubMed

    Gründemann, Jan; Clark, Beverley A

    2015-09-22

    Functional connectivity between brain regions relies on long-range signaling by myelinated axons. This is secured by saltatory action potential propagation that depends fundamentally on sodium channel availability at nodes of Ranvier. Although various potassium channel types have been anatomically localized to myelinated axons in the brain, direct evidence for their functional recruitment in maintaining node excitability is scarce. Cerebellar Purkinje cells provide continuous input to their targets in the cerebellar nuclei, reliably transmitting axonal spikes over a wide range of rates, requiring a constantly available pool of nodal sodium channels. We show that the recruitment of calcium-activated potassium channels (IK, K(Ca)3.1) by local, activity-dependent calcium (Ca(2+)) influx at nodes of Ranvier via a T-type voltage-gated Ca(2+) current provides a powerful mechanism that likely opposes depolarizing block at the nodes and is thus pivotal to securing continuous axonal spike propagation in spontaneously firing Purkinje cells.

  2. Calcium-Activated Potassium Channels at Nodes of Ranvier Secure Axonal Spike Propagation

    PubMed Central

    Gründemann, Jan; Clark, Beverley A.

    2015-01-01

    Summary Functional connectivity between brain regions relies on long-range signaling by myelinated axons. This is secured by saltatory action potential propagation that depends fundamentally on sodium channel availability at nodes of Ranvier. Although various potassium channel types have been anatomically localized to myelinated axons in the brain, direct evidence for their functional recruitment in maintaining node excitability is scarce. Cerebellar Purkinje cells provide continuous input to their targets in the cerebellar nuclei, reliably transmitting axonal spikes over a wide range of rates, requiring a constantly available pool of nodal sodium channels. We show that the recruitment of calcium-activated potassium channels (IK, KCa3.1) by local, activity-dependent calcium (Ca2+) influx at nodes of Ranvier via a T-type voltage-gated Ca2+ current provides a powerful mechanism that likely opposes depolarizing block at the nodes and is thus pivotal to securing continuous axonal spike propagation in spontaneously firing Purkinje cells. PMID:26344775

  3. Epac activator critically regulates action potential duration by decreasing potassium current in rat adult ventricle.

    PubMed

    Brette, Fabien; Blandin, Erick; Simard, Christophe; Guinamard, Romain; Sallé, Laurent

    2013-04-01

    Sympathetic stimulation is an important modulator of cardiac function via the classic cAMP-dependent signaling pathway, PKA. Recently, this paradigm has been challenged by the discovery of a family of guanine nucleotide exchange proteins directly activated by cAMP (Epac), acting in parallel to the classic signaling pathway. In cardiac myocytes, Epac activation is known to modulate Ca(2+) cycling yet their actions on cardiac ionic currents remain poorly characterized. This study attempts to address this paucity of information using the patch clamp technique to record action potential (AP) and ionic currents on rat ventricular myocytes. Epac was selectively activated by 8-CPT-AM (acetoxymethyl ester form of 8-CPT). AP amplitude, maximum depolarization rate and resting membrane amplitude were unaltered by 8-CPT-AM, strongly suggesting that Na(+) current and inward rectifier K(+) current are not regulated by Epac. In contrast, AP duration was significantly increased by 8-CPT-AM (prolongation of duration at 50% and 90% of repolarization by 41±10% and 43±8% respectively, n=11). L-type Ca(2+) current density was unaltered by 8-CPT-AM (n=16) so this cannot explain the action potential lengthening. However, the steady state component of K(+) current was significantly inhibited by 8-CPT-AM (-38±6%, n=15), while the transient outward K(+) current was unaffected by 8-CPT-AM. These effects were PKA-independent since they were observed in the presence of PKA inhibitor KT5720. Isoprenaline (100nM) induced a significant prolongation of AP duration, even in the presence of KT5720. This study provides the first evidence that the cAMP-binding protein Epac critically modulates cardiac AP duration by decreasing steady state K(+) current. These observations may be relevant to diseases in which Epac is upregulated, like cardiac hypertrophy.

  4. The Influence of Glutamate on Axonal Compound Action Potential In Vitro

    PubMed Central

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs. PMID:28077958

  5. Targeting intracellular p-aminobenzoic acid production potentiates the anti-tubercular action of antifolates

    PubMed Central

    Thiede, Joshua M.; Kordus, Shannon L.; Turman, Breanna J.; Buonomo, Joseph A.; Aldrich, Courtney C.; Minato, Yusuke; Baughn, Anthony D.

    2016-01-01

    The ability to revitalize and re-purpose existing drugs offers a powerful approach for novel treatment options against Mycobacterium tuberculosis and other infectious agents. Antifolates are an underutilized drug class in tuberculosis (TB) therapy, capable of disrupting the biosynthesis of tetrahydrofolate, an essential cellular cofactor. Based on the observation that exogenously supplied p-aminobenzoic acid (PABA) can antagonize the action of antifolates that interact with dihydropteroate synthase (DHPS), such as sulfonamides and p-aminosalicylic acid (PAS), we hypothesized that bacterial PABA biosynthesis contributes to intrinsic antifolate resistance. Herein, we demonstrate that disruption of PABA biosynthesis potentiates the anti-tubercular action of DHPS inhibitors and PAS by up to 1000 fold. Disruption of PABA biosynthesis is also demonstrated to lead to loss of viability over time. Further, we demonstrate that this strategy restores the wild type level of PAS susceptibility in a previously characterized PAS resistant strain of M. tuberculosis. Finally, we demonstrate selective inhibition of PABA biosynthesis in M. tuberculosis using the small molecule MAC173979. This study reveals that the M. tuberculosis PABA biosynthetic pathway is responsible for intrinsic resistance to various antifolates and this pathway is a chemically vulnerable target whose disruption could potentiate the tuberculocidal activity of an underutilized class of antimicrobial agents. PMID:27905500

  6. From damage response to action potentials: early evolution of neural and contractile modules in stem eukaryotes

    PubMed Central

    Brunet, Thibaut; Arendt, Detlev

    2016-01-01

    Eukaryotic cells convert external stimuli into membrane depolarization, which in turn triggers effector responses such as secretion and contraction. Here, we put forward an evolutionary hypothesis for the origin of the depolarization–contraction–secretion (DCS) coupling, the functional core of animal neuromuscular circuits. We propose that DCS coupling evolved in unicellular stem eukaryotes as part of an ‘emergency response’ to calcium influx upon membrane rupture. We detail how this initial response was subsequently modified into an ancient mechanosensory–effector arc, present in the last eukaryotic common ancestor, which enabled contractile amoeboid movement that is widespread in extant eukaryotes. Elaborating on calcium-triggered membrane depolarization, we reason that the first action potentials evolved alongside the membrane of sensory-motile cilia, with the first voltage-sensitive sodium/calcium channels (Nav/Cav) enabling a fast and coordinated response of the entire cilium to mechanosensory stimuli. From the cilium, action potentials then spread across the entire cell, enabling global cellular responses such as concerted contraction in several independent eukaryote lineages. In animals, this process led to the invention of mechanosensory contractile cells. These gave rise to mechanosensory receptor cells, neurons and muscle cells by division of labour and can be regarded as the founder cell type of the nervous system. PMID:26598726

  7. Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials

    PubMed Central

    Trantidou, Tatiana; Terracciano, Cesare M.; Kontziampasis, Dimitrios; Humphrey, Eleanor J.; Prodromakis, Themistoklis

    2015-01-01

    Current platforms for in vitro drug development utilize confluent, unorganized monolayers of heart cells to study the effect on action potential propagation. However, standard cell cultures are of limited use in cardiac research, as they do not preserve important structural and functional properties of the myocardium. Here we present a method to integrate a scaffolding technology with multi-electrode arrays and deliver a compact, off-the-shelf monitoring platform for growing biomimetic cardiac tissue. Our approach produces anisotropic cultures with conduction velocity (CV) profiles that closer resemble native heart tissue; the fastest impulse propagation is along the long axis of the aligned cardiomyocytes (CVL) and the slowest propagation is perpendicular (CVT), in contrast to standard cultures where action potential propagates isotropically (CVL ≈ CVT). The corresponding anisotropy velocity ratios (CVL/CVT = 1.38 – 2.22) are comparable with values for healthy adult rat ventricles (1.98 – 3.63). The main advantages of this approach are that (i) it provides ultimate pattern control, (ii) it is compatible with automated manufacturing steps and (iii) it is utilized through standard cell culturing protocols. Our platform is compatible with existing read-out equipment and comprises a prompt method for more reliable CV studies. PMID:26053434

  8. Action-potential-independent GABAergic tone mediated by nicotinic stimulation of immature striatal miniature synaptic transmission.

    PubMed

    Liu, Zhi; Otsu, Yo; Vasuta, Cristina; Nawa, Hiroyuki; Murphy, Timothy H

    2007-08-01

    Stimulation of presynaptic nicotinic acetylcholine receptors (nAChRs) increases the frequency of miniature excitatory synaptic activity (mEPSCs) to a point where they can promote cell firing in hippocampal CA3 neurons. We have evaluated whether nicotine regulation of miniature synaptic activity can be extended to inhibitory transmission onto striatal medium spiny projection neurons (MSNs) in acute brain slices. Bath application of micromolar nicotine typically induced 12-fold increases in the frequency of miniature inhibitory synaptic currents (mIPSCs). Little effect was observed on the amplitude of mIPSCs or mEPSCs under these conditions. Nicotine stimulation of mIPSCs was dependent on entry of extracellular calcium because removal of calcium from perfusate was able to block its action. To assess the potential physiological significance of the nicotine-stimulated increase in mIPSC frequency, we also examined the nicotine effect on evoked IPSCs (eIPSCs). eIPSCs were markedly attenuated by nicotine. This effect could be attributed to two potential mechanisms: transmitter depletion due to extremely high mIPSC rates and/or a reduction in presynaptic excitability associated with nicotinic depolarization. Treatment with low concentrations of K(+) was able to in part mimic nicotine's stimulatory effect on mIPSCs and inhibitory effect on eIPSCs. Current-clamp recordings confirmed a direct depolarizing action of nicotine that could dampen eIPSC activity leading to a switch to striatal inhibitory synaptic transmission mediated by tonic mIPSCs.

  9. Amphetamine augments action potential-dependent dopaminergic signaling in the striatum in vivo.

    PubMed

    Ramsson, Eric S; Covey, Daniel P; Daberkow, David P; Litherland, Melissa T; Juliano, Steven A; Garris, Paul A

    2011-06-01

    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 K(m) and V(max) 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.

  10. Applications of control theory to the dynamics and propagation of cardiac action potentials.

    PubMed

    Muñoz, Laura M; Stockton, Jonathan F; Otani, Niels F

    2010-09-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed.

  11. Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Patwardhan, Abhijit

    2016-01-01

    Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs. PMID:26779035

  12. Applications of Control Theory to the Dynamics and Propagation of Cardiac Action Potentials

    PubMed Central

    Muñoz, Laura M.; Stockton, Jonathan F.; Otani, Niels F.

    2011-01-01

    Sudden cardiac arrest is a widespread cause of death in the industrialized world. Most cases of sudden cardiac arrest are due to ventricular fibrillation (VF), a lethal cardiac arrhythmia. Electrophysiological abnormalities such as alternans (a beat-to-beat alternation in action potential duration) and conduction block have been suspected to contribute to the onset of VF. This study focuses on the use of control-systems techniques to analyze and design methods for suppressing these precursor factors. Control-systems tools, specifically controllability analysis and Lyapunov stability methods, were applied to a two-variable Karma model of the action-potential (AP) dynamics of a single cell, to analyze the effectiveness of strategies for suppressing AP abnormalities. State-feedback-integral (SFI) control was then applied to a Purkinje fiber simulated with the Karma model, where only one stimulating electrode was used to affect the system. SFI control converted both discordant alternans and 2:1 conduction block back toward more normal patterns, over a wider range of fiber lengths and pacing intervals compared with a Pyragas-type chaos controller. The advantages conferred by using feedback from multiple locations in the fiber, and using integral (i.e., memory) terms in the controller, are discussed. PMID:20407833

  13. Frequency-dependent inhibition of antidromic hippocampal compound action potentials by anti-convulsants.

    PubMed

    Teriakidis, Adrianna; Brown, Jon T; Randall, Andrew

    2006-01-01

    Using rat hippocampal slices, extracellularly recorded antidromic compound action potentials (cAP) were produced in CA1 pyramidal cell populations by electrical stimulation of the alveus at 0.5 Hz. These responses were additionally examined across a range of stimulus frequencies between 0.5 and 100 Hz. Anticonvulsant drugs in clinical use were applied via perfusion of the recording chamber. Three anticonvulsants produced a concentration-dependent inhibition of the cAP evoked at low frequency (0.5 Hz). The following IC(50) values were observed: lamotrigine, 210 microM (interpolated); carbamazepine, 210 microM (interpolated); phenytoin, 400 microM (extrapolated). The extent of inhibition produced was increased when trains of 30 cAPs were evoked at frequencies > or 30 Hz. This frequency dependence was quantified by measuring a response integral for a range of compound concentrations. Three other compounds valproate (5 mM), topiramate (500 microM) and levetiracetam (500 microM) produced no clear effect at any stimulus frequency tested. Using this simple neurophysiological assay it has been possible to compare the use-dependent inhibition of hippocampal action potentials by a range of anticonvulsants, providing a useful adjunct to patch clamp studies of such molecules at Na(+) channels. There is no clear correlation between the activity in this model and the clinical efficacy of these drugs in different forms of epilepsy.

  14. The use of sensory action potential to evaluate inferior alveolar nerve damage after orthognathic surgery.

    PubMed

    Calabria, Francesca; Sellek, Lucy; Gugole, Fabio; Trevisiol, Lorenzo; Trevisol, Lorenzo; Bertolasi, Laura; D'Agostino, Antonio

    2013-03-01

    To assess and monitor the common event of neurosensory disturbance to the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy, we used clinical sensory tests and neurophysiologic test sensory action potentials. The diagnostic value of these tests was evaluated by comparing them with the degree of nerve damage reported by patients. Fourteen patients undergoing bilateral sagittal split osteotomy were analyzed preoperatively and 2 years postoperatively. Patients were evaluated bilaterally for positive and negative symptoms: light touch sensation, paraesthesia, hyperesthesia, and dysaesthesia; a "sensation score" was then calculated for each patient. Patients were also asked if they would be willing to repeat the procedure knowing the sensation loss they had now. Next, the right and left IAN were evaluated using sensory action potential and correlated with the other results. Before surgery, the medium latency difference between left and right was lower compared with postsurgery, with all patients having some deficit. The reduction in medium amplitude of 67% after the intervention was statistically significant. The frequency of abnormal findings in the electrophysiologic tests indicating IAN injury correlated with subjective sensory alteration. All patients said that they would repeat the surgery. Electrophysiologic testing is recommended for the evaluation of nerve dysfunction and seems a sensitive method for accurately assessing postsurgical nerve conduction.

  15. 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.

  16. Modulation of action potential and calcium signaling by levetiracetam in rat sensory neurons.

    PubMed

    Ozcan, Mete; Ayar, Ahmet

    2012-06-01

    Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca(2+)](i). This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.

  17. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats.

    PubMed

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J; Ney, Denise M

    2009-11-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral nutrition (PN)-induced mucosal hypoplasia. The objective was to determine what enteral protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2 plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity and gain of body weigh