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Sample records for action potentials spikes

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

    PubMed Central

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

    2008-01-01

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

  2. Somatic spikes regulate dendritic signaling in small neurons in the absence of backpropagating action potentials

    PubMed Central

    Myoga, Michael H.; Beierlein, Michael; Regehr, Wade G.

    2010-01-01

    Somatic spiking is known to regulate dendritic signaling and associative synaptic plasticity in many types of large neurons, but it is unclear whether somatic action potentials play similar roles in small neurons. Here we ask whether somatic action potentials can also influence dendritic signaling in an electrically compact neuron, the cerebellar stellate cell (SC). Experiments were conducted in rat brain slices using a combination of imaging and electrophysiology. We find that somatic action potentials elevate dendritic calcium levels in SCs. There was little attenuation of calcium signals with distance from the soma in SCs from P17-19 rats, which had dendrites that averaged 60 µm in length and in short SC dendrites from P30-33 rats. Somatic action potentials evoke dendritic calcium increases that are not affected by blocking dendritic sodium channels. This indicates that dendritic signals in SCs do not rely on dendritic sodium channels, which differs from many types of large neurons where dendritic sodium channels and backpropagating action potentials allow somatic spikes to control dendritic calcium signaling. Despite the lack of active backpropagating action potentials, we find that trains of somatic action potentials elevate dendritic calcium sufficiently to release endocannabinoids and retrogradely suppress parallel fiber to SC synapses in P17-19 rats. Prolonged SC firing at physiologically realistic frequencies produces retrograde suppression when combined with low-level group I metabotropic glutamate receptor activation. Somatic spiking also interacts with synaptic stimulation to promote associative plasticity. These findings indicate that in small neurons the passive spread of potential within dendrites can allow somatic spiking to regulate dendritic calcium signaling and synaptic plasticity. PMID:19535592

  3. Dynamics of action potential firing in electrically connected striatal fast-spiking interneurons

    PubMed Central

    Russo, Giovanni; Nieus, Thierry R.; Maggi, Silvia; Taverna, Stefano

    2013-01-01

    Fast-spiking interneurons (FSIs) play a central role in organizing the output of striatal neural circuits, yet functional interactions between these cells are still largely unknown. Here we investigated the interplay of action potential (AP) firing between electrically connected pairs of identified FSIs in mouse striatal slices. In addition to a loose coordination of firing activity mediated by membrane potential coupling, gap junctions (GJ) induced a frequency-dependent inhibition of spike discharge in coupled cells. At relatively low firing rates (2–20 Hz), some APs were tightly synchronized whereas others were inhibited. However, burst firing at intermediate frequencies (25–60 Hz) mostly induced spike inhibition, while at frequencies >50–60 Hz FSI pairs tended to synchronize. Spike silencing occurred even in the absence of GABAergic synapses or persisted after a complete block of GABAA receptors. Pharmacological suppression of presynaptic spike afterhyperpolarization (AHP) caused postsynaptic spikelets to become more prone to trigger spikes at near-threshold potentials, leading to a mostly synchronous firing activity. The complex pattern of functional coordination mediated by GJ endows FSIs with peculiar dynamic properties that may be critical in controlling striatal-dependent behavior. PMID:24294191

  4. 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.

  5. 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

  6. 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

  7. 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...

  8. Influence of spiking activity on cortical local field potentials

    PubMed Central

    Waldert, Stephan; Lemon, Roger N; Kraskov, Alexander

    2013-01-01

    The intra-cortical local field potential (LFP) reflects a variety of electrophysiological processes including synaptic inputs to neurons and their spiking activity. It is still a common assumption that removing high frequencies, often above 300 Hz, is sufficient to exclude spiking activity from LFP activity prior to analysis. Conclusions based on such supposedly spike-free LFPs can result in false interpretations of neurophysiological processes and erroneous correlations between LFPs and behaviour or spiking activity. Such findings might simply arise from spike contamination rather than from genuine changes in synaptic input activity. Although the subject of recent studies, the extent of LFP contamination by spikes is unclear, and the fundamental problem remains. Using spikes recorded in the motor cortex of the awake monkey, we investigated how different factors, including spike amplitude, duration and firing rate, together with the noise statistic, can determine the extent to which spikes contaminate intra-cortical LFPs. We demonstrate that such contamination is realistic for LFPs with a frequency down to ∼10 Hz. For LFP activity below ∼10 Hz, such as movement-related potential, contamination is theoretically possible but unlikely in real situations. Importantly, LFP frequencies up to the (high-) gamma band can remain unaffected. This study shows that spike–LFP crosstalk in intra-cortical recordings should be assessed for each individual dataset to ensure that conclusions based on LFP analysis are valid. To this end, we introduce a method to detect and to visualise spike contamination, and provide a systematic guide to assess spike contamination of intra-cortical LFPs. PMID:23981719

  9. Learning of Precise Spike Times with Homeostatic Membrane Potential Dependent Synaptic Plasticity

    PubMed Central

    Albers, Christian; Westkott, Maren; Pawelzik, Klaus

    2016-01-01

    Precise spatio-temporal patterns of neuronal action potentials underly e.g. sensory representations and control of muscle activities. However, it is not known how the synaptic efficacies in the neuronal networks of the brain adapt such that they can reliably generate spikes at specific points in time. Existing activity-dependent plasticity rules like Spike-Timing-Dependent Plasticity are agnostic to the goal of learning spike times. On the other hand, the existing formal and supervised learning algorithms perform a temporally precise comparison of projected activity with the target, but there is no known biologically plausible implementation of this comparison. Here, we propose a simple and local unsupervised synaptic plasticity mechanism that is derived from the requirement of a balanced membrane potential. Since the relevant signal for synaptic change is the postsynaptic voltage rather than spike times, we call the plasticity rule Membrane Potential Dependent Plasticity (MPDP). Combining our plasticity mechanism with spike after-hyperpolarization causes a sensitivity of synaptic change to pre- and postsynaptic spike times which can reproduce Hebbian spike timing dependent plasticity for inhibitory synapses as was found in experiments. In addition, the sensitivity of MPDP to the time course of the voltage when generating a spike allows MPDP to distinguish between weak (spurious) and strong (teacher) spikes, which therefore provides a neuronal basis for the comparison of actual and target activity. For spatio-temporal input spike patterns our conceptually simple plasticity rule achieves a surprisingly high storage capacity for spike associations. The sensitivity of the MPDP to the subthreshold membrane potential during training allows robust memory retrieval after learning even in the presence of activity corrupted by noise. We propose that MPDP represents a biophysically plausible mechanism to learn temporal target activity patterns. PMID:26900845

  10. Joint analysis of spikes and local field potentials using copula.

    PubMed

    Hu, Meng; Li, Mingyao; Li, Wu; Liang, Hualou

    2016-06-01

    Recent technological advances, which allow for simultaneous recording of spikes and local field potentials (LFPs) at multiple sites in a given cortical area or across different areas, have greatly increased our understanding of signal processing in brain circuits. Joint analysis of simultaneously collected spike and LFP signals is an important step to explicate how the brain orchestrates information processing. In this contribution, we present a novel statistical framework based on Gaussian copula to jointly model spikes and LFP. In our approach, we use copula to link separate, marginal regression models to construct a joint regression model, in which the binary-valued spike train data are modeled using generalized linear model (GLM) and the continuous-valued LFP data are modeled using linear regression. Model parameters can be efficiently estimated via maximum-likelihood. In particular, we show that our model offers a means to statistically detect directional influence between spikes and LFP, akin to Granger causality measure, and that we are able to assess its statistical significance by conducting a Wald test. Through extensive simulations, we also show that our method is able to reliably recover the true model used to generate the data. To demonstrate the effectiveness of our approach in real setting, we further apply the method to a mixed neural dataset, consisting of spikes and LFP simultaneously recorded from the visual cortex of a monkey performing a contour detection task. PMID:27012500

  11. Multiple Spike Time Patterns Occur at Bifurcation Points of Membrane Potential Dynamics

    PubMed Central

    Toups, J. Vincent; Fellous, Jean-Marc; Thomas, Peter J.; Sejnowski, Terrence J.; Tiesinga, Paul H.

    2012-01-01

    The response of a neuron to repeated somatic fluctuating current injections in vitro can elicit a reliable and precisely timed sequence of action potentials. The set of responses obtained across trials can also be interpreted as the response of an ensemble of similar neurons receiving the same input, with the precise spike times representing synchronous volleys that would be effective in driving postsynaptic neurons. To study the reproducibility of the output spike times for different conditions that might occur in vivo, we somatically injected aperiodic current waveforms into cortical neurons in vitro and systematically varied the amplitude and DC offset of the fluctuations. As the amplitude of the fluctuations was increased, reliability increased and the spike times remained stable over a wide range of values. However, at specific values called bifurcation points, large shifts in the spike times were obtained in response to small changes in the stimulus, resulting in multiple spike patterns that were revealed using an unsupervised classification method. Increasing the DC offset, which mimicked an overall increase in network background activity, also revealed bifurcation points and increased the reliability. Furthermore, the spike times shifted earlier with increasing offset. Although the reliability was reduced at bifurcation points, a theoretical analysis showed that the information about the stimulus time course was increased because each of the spike time patterns contained different information about the input. PMID:23093916

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

  13. 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.

  14. NMDA spike/plateau potentials in dendrites of thalamocortical neurons.

    PubMed

    Augustinaite, Sigita; Kuhn, Bernd; Helm, Paul Johannes; Heggelund, Paul

    2014-08-13

    Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal neurons, provide supralinear integration of synaptic inputs on thin and distal dendrites, thereby increasing the impact of these inputs on the soma. The more specific functional role of these potentials has been difficult to clarify, partly due to the complex circuitry of cortical neurons. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus participate in simpler circuits. They receive their primary afferent input from retina and send their output to visual cortex. Cortex, in turn, regulates this output through massive feedback to distal dendrites of the TC neurons. The TC neurons can operate in two modes related to behavioral states: burst mode prevailing during sleep, when T-type calcium bursts largely disrupt the transfer of signals from retina to cortex, and tonic mode, which provides reliable transfer of retinal signals to cortex during wakefulness. We studied dendritic potentials in TC neurons with combined two-photon calcium imaging and whole-cell recording of responses to local dendritic glutamate iontophoresis in acute brain slices from mice. We found that NMDA spike/plateaus can be elicited locally at distal dendrites of TC neurons. We suggest that these dendritic potentials have important functions in the cortical regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts in the functional mode from burst to tonic by blockade of T-type calcium conductances. Moreover, in tonic mode, they can facilitate the transfer of retinal signals to cortex by depolarization of TC neurons. PMID:25122891

  15. Code-specific learning rules improve action selection by populations of spiking neurons.

    PubMed

    Friedrich, Johannes; Urbanczik, Robert; Senn, Walter

    2014-08-01

    Population coding is widely regarded as a key mechanism for achieving reliable behavioral decisions. We previously introduced reinforcement learning for population-based decision making by spiking neurons. Here we generalize population reinforcement learning to spike-based plasticity rules that take account of the postsynaptic neural code. We consider spike/no-spike, spike count and spike latency codes. The multi-valued and continuous-valued features in the postsynaptic code allow for a generalization of binary decision making to multi-valued decision making and continuous-valued action selection. We show that code-specific learning rules speed up learning both for the discrete classification and the continuous regression tasks. The suggested learning rules also speed up with increasing population size as opposed to standard reinforcement learning rules. Continuous action selection is further shown to explain realistic learning speeds in the Morris water maze. Finally, we introduce the concept of action perturbation as opposed to the classical weight- or node-perturbation as an exploration mechanism underlying reinforcement learning. Exploration in the action space greatly increases the speed of learning as compared to exploration in the neuron or weight space. PMID:24875790

  16. Enhanced high-frequency membrane potential fluctuations control spike output in striatal fast-spiking interneurones in vivo.

    PubMed

    Schulz, Jan M; Pitcher, Toni L; Savanthrapadian, Shakuntala; Wickens, Jeffery R; Oswald, Manfred J; Reynolds, John N J

    2011-09-01

    Fast-spiking interneurones (FSIs) constitute a prominent part of the inhibitory microcircuitry of the striatum; however, little is known about their recruitment by synaptic inputs in vivo. Here, we report that, in contrast to cholinergic interneurones (CINs), FSIs (n = 9) recorded in urethane-anaesthetized rats exhibit Down-to-Up state transitions very similar to spiny projection neurones (SPNs). Compared to SPNs, the FSI Up state membrane potential was noisier and power spectra exhibited significantly larger power at frequencies in the gamma range (55-95 Hz). The membrane potential exhibited short and steep trajectories preceding spontaneous spike discharge, suggesting that fast input components controlled spike output in FSIs. Spontaneous spike data contained a high proportion (43.6 ± 32.8%) of small inter-spike intervals (ISIs) of <30 ms, setting FSIs clearly apart from SPNs and CINs. Cortical-evoked inputs had slower dynamics in SPNs than FSIs, and repetitive stimulation entrained SPN spike output only if the stimulation was delivered at an intermediate frequency (20 Hz), but not at a high frequency (100 Hz). Pharmacological induction of an activated ECoG state, known to promote rapid FSI spiking, mildly increased the power (by 43 ± 55%, n = 13) at gamma frequencies in the membrane potential of SPNs, but resulted in few small ISIs (<30 ms; 4.3 ± 6.4%, n = 8). The gamma frequency content did not change in CINs (n = 8). These results indicate that FSIs are uniquely responsive to high-frequency input sequences. By controlling the spike output of SPNs, FSIs could serve gating of top-down signals and long-range synchronisation of gamma-oscillations during behaviour. PMID:21746788

  17. Localization of single-cell current sources based on extracellular potential patterns: the spike CSD method.

    PubMed

    Somogyvári, Zoltán; Cserpán, Dorottya; Ulbert, István; Erdi, Péter

    2012-11-01

    Traditional current source density (tCSD) calculation method calculates neural current source distribution of extracellular (EC) potential patterns, thus providing important neurophysiological information. While the tCSD method is based on physical principles, it adopts some assumptions, which can not hold for single-cell activity. Consequently, tCSD method gives false results for single-cell activity. A new, spike CSD (sCSD) method has been developed, specifically designed to reveal CSD distribution of single cells during action potential generation. This method is based on the inverse solution of the Poisson-equation. The efficiency of the method is tested and demonstrated with simulations, and showed, that the sCSD method reconstructed the original CSD more precisely than the tCSD. The sCSD method is applied to EC spatial potential patterns of spikes, measured in cat primary auditory cortex with a 16-channel chronically implanted linear probe in vivo. Using our method, the cell-electrode distances were estimated and the spatio-temporal CSD distributions were reconstructed. The results suggested, that the new method is potentially useful in determining fine details of the spatio-temporal dynamics of spikes. PMID:22934892

  18. 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

  19. 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.

  20. 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

  1. Synaptic action of R beta neurons on phrenic motoneurons studied with spike-triggered averaging.

    PubMed

    Lipski, J; Kubin, L; Jodkowski, J

    1983-12-12

    The functional role of dorsal medullary inspiratory neurons with excitatory input from lung stretch receptors (R beta neurons) is a matter of controversy. The present study, performed on chloralose-anesthetized and paralyzed cats, ventilated mainly with a phrenic-controlled servorespirator, deals with the spinal projection of these neurons, a property which suggests their involvement in the efferent part of the medullary respiratory complex. Out of 37 inspiratory neurons which could be excited antidromically following microstimulation within the contralateral C6 phrenic nucleus (latency 2.0 ms +/- 0.4, S.D.), 17 were classified by the 'no-inflation' test as R beta. Intracellular recording of synaptic potentials from phrenic motoneurons using the 'spike-triggered averaging' technique were made. In 10 phrenic motoneurons, the averaging revealed individual EPSPs (peak amplitude 150 +/- 110 microV, rise time 0.5 +/- 0.2 ms) time-locked to action potentials of 5 out of 7 R beta neurons tested. Cross-correlation of the R beta neurons firing with the activity of C5 and C6 phrenic rootlets indicated a divergence of excitatory action within the phrenic nucleus. For comparison, in 3 phrenic motoneurons individual EPSPs were recorded when the activity of 3 R alpha cells was used to trigger the averaging. It is concluded that at least some R beta neurons, similarly to R alpha neurons, project to the contralateral phrenic nucleus and can make monosynaptic excitatory connections with phrenic motoneurons. The finding that individual EPSPs were similar when averaging was triggered by the activity of either R beta or R alpha neurons provides new evidence for our earlier hypothesis that bulbospinal inspiratory neurons of the solitary tract nucleus may be subdivided into two categories only on a quantitative basis. PMID:6661613

  2. Spike-Threshold Adaptation Predicted by Membrane Potential Dynamics In Vivo

    PubMed Central

    Fontaine, Bertrand; Peña, José Luis; Brette, Romain

    2014-01-01

    Neurons encode information in sequences of spikes, which are triggered when their membrane potential crosses a threshold. In vivo, the spiking threshold displays large variability suggesting that threshold dynamics have a profound influence on how the combined input of a neuron is encoded in the spiking. Threshold variability could be explained by adaptation to the membrane potential. However, it could also be the case that most threshold variability reflects noise and processes other than threshold adaptation. Here, we investigated threshold variation in auditory neurons responses recorded in vivo in barn owls. We found that spike threshold is quantitatively predicted by a model in which the threshold adapts, tracking the membrane potential at a short timescale. As a result, in these neurons, slow voltage fluctuations do not contribute to spiking because they are filtered by threshold adaptation. More importantly, these neurons can only respond to input spikes arriving together on a millisecond timescale. These results demonstrate that fast adaptation to the membrane potential captures spike threshold variability in vivo. PMID:24722397

  3. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    PubMed Central

    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. PMID:22511855

  4. Action potential broadening in a presynaptic channelopathy.

    PubMed

    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 Ca(2+) influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. PMID:27381274

  5. 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

  6. 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.

  7. Axon initial segment Ca2+ channels influence action potential generation and timing

    PubMed Central

    Bender, Kevin J.; Trussell, Laurence O.

    2009-01-01

    Summary Although action potentials are typically generated in the axon initial segment (AIS), the timing and pattern of action potentials is thought to depend on inward current originating in somatodendritic compartments. Using 2-photon imaging, we show that T- and R-type voltage-gated Ca2+ channels are co-localized with Na+ channels in the AIS of dorsal cochlear nucleus interneurons, and that activation of these Ca2+ channels is essential to the generation and timing of action potential bursts known as complex spikes. During complex spikes, where Na+-mediated spikelets fire atop slower depolarizing conductances, selective block of AIS Ca2+ channels delays spike timing and raises spike threshold. Furthermore, AIS Ca2+ channel block can decrease the number of spikelets within a complex spike, and even block single, simple spikes. Similar results were found in cortex and cerebellum. Thus, voltage-gated Ca2+ channels at the site of spike initiation play a key role in generating and shaping spike bursts. PMID:19186168

  8. Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

    PubMed Central

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

  9. Consequences of converting graded to action potentials upon neural information coding and energy efficiency.

    PubMed

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

  10. Signal reconstruction of the slow wave and spike potential from electrogastrogram.

    PubMed

    Qin, Shujia; Ding, Wei; Miao, Lei; Xi, Ning; Li, Hongyi; Yang, Chunmin

    2015-01-01

    The gastric slow wave and the spike potential can correspondingly represent the rhythm and the intensity of stomach motility. Because of the filtering effect of biological tissue, electrogastrogram (EGG) cannot measure the spike potential on the abdominal surface in the time domain. Thus, currently the parameters of EGG adopted by clinical applications are only the characteristics of the slow wave, such as the dominant frequency, the dominant power and the instability coefficients. The limitation of excluding the spike potential analyses hinders EGG from being a diagnosis to comprehensively reveal the motility status of the stomach. To overcome this defect, this paper a) presents an EGG reconstruction method utilizing the specified signal components decomposed by the discrete wavelet packet transform, and b) obtains a frequency band for the human gastric spike potential through fasting and postprandial cutaneous EGG experiments for twenty-five human volunteers. The results indicate the lower bound of the human gastric spike potential frequency is 0.96±0.20 Hz (58±12 cpm), and the upper bound is 1.17±0.23 Hz (70±14 cpm), both of which have not been reported before to the best of our knowledge. As an auxiliary validation of the proposed method, synchronous serosa-surface EGG acquisitions are carried out for two dogs. The frequency band results for the gastric spike potential of the two dogs are respectively 0.83-0.90 Hz (50-54 cpm) and 1.05-1.32 Hz (63-79 cpm). They lie in the reference range 50-80 cpm proposed in previous literature, showing the feasibility of the reconstruction method in this paper. PMID:26405915

  11. [Ion channels and action potentials in olfactory receptor cells].

    PubMed

    Kawai, Fusao; Miyachi, Ei-ichi

    2007-11-01

    The first step in olfactory sensation involves the binding of odorant molecules to specific receptor proteins on the ciliary surface of olfactory receptor cells (ORCs). Odorant receptors coupled to G-proteins activate adenylyl cyclase leading to the generation of cAMP, which directly gates a cyclic nucleotide-gated cationic channel in the ciliary membrane. This initial excitation causes a slow and graded depolarizing voltage change, which is encoded into a train of action potentials. Action potentials of ORCs are generated by voltage-gated Na- currents and T-type Ca2- currents in the somatic membrane. Isolated ORCs that have lost their cilia during the dissociation procedure are known to exhibit spike frequency accommodation by injecting the steady current. This raises the possibility that somatic ionic channels in ORCs may serve for odor adaptation at the level of spike encoding, although odor adaptation is mainly accomplished by the ciliary transduction machinery. This review discusses current knowledge concerning the mechanisms of spike generation in ORCs. It also reviews how neurotransmitters and hormones modulate ionic currents and action potentials in ORCs. PMID:18154041

  12. 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

  13. 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

  14. Temporal spike pattern learning

    NASA Astrophysics Data System (ADS)

    Talathi, Sachin S.; Abarbanel, Henry D. I.; Ditto, William L.

    2008-09-01

    Sensory systems pass information about an animal’s environment to higher nervous system units through sequences of action potentials. When these action potentials have essentially equivalent wave forms, all information is contained in the interspike intervals (ISIs) of the spike sequence. How do neural circuits recognize and read these ISI sequences? We address this issue of temporal sequence learning by a neuronal system utilizing spike timing dependent plasticity (STDP). We present a general architecture of neural circuitry that can perform the task of ISI recognition. The essential ingredients of this neural circuit, which we refer to as “interspike interval recognition unit” (IRU) are (i) a spike selection unit, the function of which is to selectively distribute input spikes to downstream IRU circuitry; (ii) a time-delay unit that can be tuned by STDP; and (iii) a detection unit, which is the output of the IRU and a spike from which indicates successful ISI recognition by the IRU. We present two distinct configurations for the time-delay circuit within the IRU using excitatory and inhibitory synapses, respectively, to produce a delayed output spike at time t0+τ(R) in response to the input spike received at time t0 . R is the tunable parameter of the time-delay circuit that controls the timing of the delayed output spike. We discuss the forms of STDP rules for excitatory and inhibitory synapses, respectively, that allow for modulation of R for the IRU to perform its task of ISI recognition. We then present two specific implementations for the IRU circuitry, derived from the general architecture that can both learn the ISIs of a training sequence and then recognize the same ISI sequence when it is presented on subsequent occasions.

  15. Temporal spike pattern learning.

    PubMed

    Talathi, Sachin S; Abarbanel, Henry D I; Ditto, William L

    2008-09-01

    Sensory systems pass information about an animal's environment to higher nervous system units through sequences of action potentials. When these action potentials have essentially equivalent wave forms, all information is contained in the interspike intervals (ISIs) of the spike sequence. How do neural circuits recognize and read these ISI sequences? We address this issue of temporal sequence learning by a neuronal system utilizing spike timing dependent plasticity (STDP). We present a general architecture of neural circuitry that can perform the task of ISI recognition. The essential ingredients of this neural circuit, which we refer to as "interspike interval recognition unit" (IRU) are (i) a spike selection unit, the function of which is to selectively distribute input spikes to downstream IRU circuitry; (ii) a time-delay unit that can be tuned by STDP; and (iii) a detection unit, which is the output of the IRU and a spike from which indicates successful ISI recognition by the IRU. We present two distinct configurations for the time-delay circuit within the IRU using excitatory and inhibitory synapses, respectively, to produce a delayed output spike at time t_{0}+tau(R) in response to the input spike received at time t_{0} . R is the tunable parameter of the time-delay circuit that controls the timing of the delayed output spike. We discuss the forms of STDP rules for excitatory and inhibitory synapses, respectively, that allow for modulation of R for the IRU to perform its task of ISI recognition. We then present two specific implementations for the IRU circuitry, derived from the general architecture that can both learn the ISIs of a training sequence and then recognize the same ISI sequence when it is presented on subsequent occasions. PMID:18851076

  16. Long-term potentiation and evoked spike responses in the cingulate cortex of freely mobile rats.

    PubMed

    Gorkin, A G; Reymann, K G; Aleksandrov, Yu I

    2003-10-01

    Long-term potentiation of synaptic efficiency is regarded as a major candidate for the role of the physiological mechanism of long-term memory. However, the limited development of concepts of the cellular and subcellular characteristics of the induction of long-term potentiation in animals in conditions of free behavior does not correspond to the importance of this question. The present study was undertaken to determine whether the characteristics of potentiation in the cingulate cortex in response to stimulation of fibers of the subiculo-cingulate tract are truly long-term, i.e., develop through all known phases and last at least 24 h, in freely moving animals. In addition, the study aims included identification of the effects of application of blockers of different types of glutamate receptors on the development of long-term potentiation and identification of the characteristics of spike responses of single cingulate cortex neurons to stimulation of the subiculo-cingulate tract. Long-term potentiation, lasting more than 24 h, was obtained in freely moving adult rats not treated with GABA blockers. Injection of glutamate NMDA synapse blockers led to significant decreases in evoked cingulate cortex potentials in response to test stimulation. Activatory short-latency spike responses were characterized by a low probability of spike generation, and this increased with increases in the stimulation current. These data demonstrated that it is methodologically possible to compare, in freely moving rats, the involvement of individual neurons in the mechanisms involved in learning one or another type of adaptive behavior and the dynamics of their evoked spike activity during the formation of long-term potentiation. PMID:14635990

  17. Spatial dynamics of action potentials estimated by dendritic Ca(2+) signals in insect projection neurons.

    PubMed

    Ogawa, Hiroto; Mitani, Ruriko

    2015-11-13

    The spatial dynamics of action potentials, including their propagation and the location of spike initiation zone (SIZ), are crucial for the computation of a single neuron. Compared with mammalian central neurons, the spike dynamics of invertebrate neurons remain relatively unknown. Thus, we examined the spike dynamics based on single spike-induced Ca(2+) signals in the dendrites of cricket mechanosensory projection neurons, known as giant interneurons (GIs). The Ca(2+) transients induced by a synaptically evoked single spike were larger than those induced by an antidromic spike, whereas subthreshold synaptic potentials caused no elevation of Ca(2+). These results indicate that synaptic activity enhances the dendritic Ca(2+) influx through voltage-gated Ca(2+) channels. Stimulation of the presynaptic sensory afferents ipsilateral to the recording site evoked a dendritic spike with higher amplitude than contralateral stimulation, thereby suggesting that alteration of the spike waveform resulted in synaptic enhancement of the dendritic Ca(2+) transients. The SIZ estimated from the spatial distribution of the difference in the Ca(2+) amplitude was distributed throughout the right and left dendritic branches across the primary neurite connecting them in GIs. PMID:26456645

  18. Resting and spike potentials of skeletal muscle fibres of salt water elasmobranch and teleost fish

    PubMed Central

    Hagiwara, Susumu; Takahashi, Kunitaro

    1967-01-01

    1. Membrane properties of the muscle fibre were studied in twitch motor system of sea-water elasmobranch (Taeniura lymma, Himantura uarnak and Pastinachus sephen) and teleost fish (Periophthalmodon barbarus, Tetradon immaculata, Hemiramphus welsby, Parexocoetus brachypterus and Conger labiatus). 2. The resting potential of the elasmobranch fibre is mainly determined by the Cl- concentration difference between inside and outside the membrane whereas the K+ conductance is the determining factor in teleost fibres. 3. The resting membrane of the elasmobranch fibre is permeable not only to Cl- ions but also several other anions (Br-, I-, NO3-, SCN-, ClO4-, ClO3-) of large limiting conductivities in the aqueous solution. 4. The spike potential of the elasmobranch fibre always shows a significant overshoot in normal saline while no significant overshoot is generally found in teleost fibres. 5. In both elasmobranchs and teleosts the spike is produced by the permeability increase of the membrane to Na+ ions and is effectively suppressed by tetrodotoxin at a concentration of 0·5-1·0 × 10-7 g/ml. of the external solution with one exception, i.e. the Na+ spike of Tetradon fibre is not suppressed by the toxin even when the concentration is above 5 × 10-4 g/ml. PMID:6051784

  19. 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

  20. Pattern motion selectivity of spiking outputs and local field potentials in macaque visual cortex.

    PubMed

    Khawaja, Farhan A; Tsui, James M G; Pack, Christopher C

    2009-10-28

    The dorsal pathway of the primate visual cortex is involved in the processing of motion signals that are useful for perception and behavior. Along this pathway, motion information is first measured by the primary visual cortex (V1), which sends specialized projections to extrastriate regions such as the middle temporal area (MT). Previous work with plaid stimuli has shown that most V1 neurons respond to the individual components of moving stimuli, whereas some MT neurons are capable of estimating the global motion of the pattern. In this work, we show that the majority of neurons in the medial superior temporal area (MST), which receives input from MT, have this pattern-selective property. Interestingly, the local field potentials (LFPs) measured simultaneously with the spikes often exhibit properties similar to that of the presumptive feedforward input to each area: in the high-gamma frequency band, the LFPs in MST are as component selective as the spiking outputs of MT, and MT LFPs have plaid responses that are similar to the spiking outputs of V1. In the lower LFP frequency bands (beta and low gamma), component selectivity is very common, and pattern selectivity is almost entirely absent in both MT and MST. Together, these results suggest a surprisingly strong link between the sensory tuning of cortical LFPs and afferent inputs, with important implications for the interpretation of imaging studies and for models of cortical function. PMID:19864582

  1. Action potentials of embryonic dorsal root ganglion neurones in Xenopus tadpoles.

    PubMed Central

    Baccaglini, P I

    1978-01-01

    1. Several classes of action potentials can be distinguished in dorsal root ganglion cells, studied by intracellular recording techniques in Xenopus laevis tadpoles 4.5--51 days old. The ionic basis of the action potential was investigated by changing the ionic environment of the cells and applying various blocking agents. 2. The Ca2+-dependent action potential is a plateau of relatively long duration (mean 8.7 msec). It is unaffected by removal of Na+ but blocked by mM quantities of Co2+. It is present only in small cells. 3. Ca2+/Na+-dependent action potentials. Type I is a spike followed by a plateau or hump of different durations (mean 8.1 msec). The spike is selectively blocked by removal of Na+, leaving the plateau which is in turn blocked by Co2+. It is present in cells of small and intermediate size. Type II is a spike of short duration (mean 2.0 msec) with only an inflection on the falling phase. The spike is blocked by removal of Na+ and no other components can be elicited. The inflection is blocked by Co2+. It is present in cells of all sizes. Type III is similar to type I but is seen only in solutions in which the outward current is blocked. It was observed only very infrequently. 4. Na+-dependent action potentials. Type I a is a short duration spike (mean 1.1 msec). It is abolished by removal of Na+ or addition of tetrodotoxin (TTX), but largely unaffected by Co2+ or La3+. It is present in cells of all sizes. When the outward current channels are blocked and cells exposed to Na+-free solutions, all cells are capable of producing an action potential in which the inward current is carried by divalent cations. Type I b is a spike with a smooth, more slowly falling phase. It has the same pharmacological properties as type I a action potential and is present in cells of small size. 5. Na+-dependent action potentials. Type II is a spike with an inflection on the falling phase (mean duration 3.4 msec). It is prolonged by Co2+ and La3+. Removal of Na

  2. 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.

  3. 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

  4. Action Potentials Initiate in the Axon Initial Segment and Propagate Through Axon Collaterals Reliably in Cerebellar Purkinje Neurons

    PubMed Central

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

    2010-01-01

    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By utilizing a recent improvement in voltage sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission. PMID:20484631

  5. 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…

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

    NASA Astrophysics Data System (ADS)

    Decharms, R. Christopher; Merzenich, Michael M.

    1996-06-01

    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 synchronized1,2, which could be involved in 'binding' together individual firing-rate feature representations into a unified object percept3. 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 systematically signal stimulus features, it is topographically mapped, and it follows the stimulus time course even where mean firing rate does not.

  7. Acute NMDA receptor antagonism disrupts synchronization of action potential firing in rat prefrontal cortex.

    PubMed

    Molina, Leonardo A; Skelin, Ivan; Gruber, Aaron J

    2014-01-01

    Antagonists of N-methyl-D-aspartate receptors (NMDAR) have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801) on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists. PMID:24465743

  8. NeuroGrid: recording action potentials from the surface of the brain

    PubMed Central

    Khodagholy, Dion; Gelinas, Jennifer N.; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G.; Buzsáki, György

    2014-01-01

    Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) that can record both LFP and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding one week. We also recorded LFP-modulated spiking activity intra-operatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders. PMID:25531570

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

    PubMed

    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 Ca(2+) 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

  10. Time course of Ca and Ca-dependent K currents during molluscan nerve cell action potentials.

    PubMed

    Gola, M; Hussy, N; Crest, M; Ducreux, C

    1986-10-20

    The time courses of Ca and Ca-dependent K currents during Ca-dependent action potentials were obtained by recording the membrane currents produced in response to spike-like voltage clamp pulses before and after selective blockade of channels. The Ca current had a biphasic waveform with a first surge and a late, large entry. The Ca-dependent K(Ca) current onset was relatively fast with a peak occurring at half spike repolarization. The fast activation of the K(Ca) current was consecutive to the first Ca entry. It is concluded that K(Ca) currents constitute a powerful spike repolarization mechanism in addition to the voltage-dependent K currents. PMID:2430243

  11. 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

  12. Correlation of action potentials in adjacent neurons

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Pekker, M.

    2015-12-01

    A possible mechanism for the synchronization of action potential propagation along a bundle of neurons (ephaptic coupling) is considered. It is shown that this mechanism is similar to the salutatory conduction of the action potential between the nodes of Ranvier in myelinated axons. The proposed model allows us to estimate the scale of the correlation, i.e., the distance between neurons in the nervous tissue, wherein their synchronization becomes possible. The possibility for experimental verification of the proposed model of synchronization is discussed.

  13. Hierarchical spike clustering analysis for investigation of interneuron heterogeneity.

    PubMed

    Boehlen, Anne; Heinemann, Uwe; Henneberger, Christian

    2016-04-21

    Action potentials represent the output of a neuron. Especially interneurons display a variety of discharge patterns ranging from regular action potential firing to prominent spike clustering or stuttering. The mechanisms underlying this heterogeneity remain incompletely understood. We established hierarchical cluster analysis of spike trains as a measure of spike clustering. A clustering index was calculated from action potential trains recorded in the whole-cell patch clamp configuration from hippocampal (CA1, stratum radiatum) and entorhinal (medial entorhinal cortex, layer 2) interneurons in acute slices and simulated data. Prominent, region-dependent, but also variable spike clustering was detected using this measure. Further analysis revealed a strong positive correlation between spike clustering and membrane potentials oscillations but an inverse correlation with neuronal resonance. Furthermore, clustering was more pronounced when the balance between fast-activating K(+) currents, assessed by the spike repolarisation time, and hyperpolarization-activated currents, gauged by the size of the sag potential, was shifted in favour of fast K(+) currents. Simulations of spike clustering confirmed that variable ratios of fast K(+) and hyperpolarization-activated currents could underlie different degrees of spike clustering and could thus be crucial for temporally structuring interneuron spike output. PMID:26987719

  14. Screening Action Potentials: The Power of Light

    PubMed Central

    Kaestner, Lars; Lipp, Peter

    2011-01-01

    Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated read out and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for, e.g., pharmacological screens the following preparatory work has to be provided: (i) model cells under investigation need to represent target cells in the best possible manner; (ii) optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable read out with minimal interaction with the naive behavior of the cells and (iii) devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials. PMID:21847381

  15. 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…

  16. Transferrin: structure, function and potential therapeutic actions.

    PubMed

    Gomme, Peter T; McCann, Karl B; Bertolini, Joseph

    2005-02-15

    There are many proteins that can multi-task. Transferrin, widely known as an iron-binding protein, is one such example of a multi-tasking protein. In this review, the multiple biological actions of transferrin, including its growth and cytoprotective activities, are discussed with the view of highlighting the potential therapeutic applications of this protein. PMID:15708745

  17. Shade-Induced Action Potentials in Helianthus annuus L. Originate Primarily from the Epicotyl

    PubMed Central

    Stephens, Nicholas R; Cleland, Robert E; Van Volkenburgh, Elizabeth

    2006-01-01

    Repeated observations that shading (a drastic reduction in illumination rate) increased the generation of spikes (rapidly reversed depolarizations) in leaves and stems of many cucumber and sunflower plants suggests a phenomenon widespread among plant organs and species. Although shaded leaves occasionally generate spikes and have been suggested to trigger systemic action potentials (APs) in sunflower stems, we never found leaf-generated spikes to propagate out of the leaf and into the stem. On the contrary, our data consistently implicate the epicotyl as the location where most spikes and APs (propagating spikes) originate. Microelectrode studies of light and shading responses in mesophyll cells of leaf strips and in epidermis/cortex cells of epicotyl segments confirm this conclusion and show that spike induction is not confined to intact plants. 90% of the epicotyl-generated APs undergo basipetal propagation to the lower epicotyl, hypocotyl and root. They propagate with an average rate of 2 ± 0.3 mm s−1 and always undergo a large decrement from the hypocotyl to the root. The few epicotyl-derived APs that can be tracked to leaf blades (< 10%) undergo either a large decrement or fail to be transmitted at all. Occasionally (5% of the observations) spikes were be generated in hypocotyl and lower epicotyl that moved towards the upper epicotyl unaltered, decremented, or amplified. This study confirms that plant APs arise to natural, nontraumatic changes. In simultaneous recordings with epicotyl growth, AP generation was found to parallel the acceleration of stem growth under shade. The possible relatedness of both processes must be further investigated. PMID:19521471

  18. Mechanical surface waves accompany action potential propagation.

    PubMed

    El Hady, Ahmed; Machta, Benjamin B

    2015-01-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs. PMID:25819404

  19. Mechanical surface waves accompany action potential propagation

    NASA Astrophysics Data System (ADS)

    El Hady, Ahmed; Machta, Benjamin B.

    2015-03-01

    Many diverse studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the action potential (AP). We present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model, these surface waves are driven by the travelling wave of electrical depolarization characterizing the AP, altering compressive electrostatic forces across the membrane. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model allows us to estimate the shape of the AW that accompanies any travelling wave of voltage, making predictions that are in agreement with results from several experimental systems. Our model can serve as a framework for understanding the physical origins and possible functional roles of these AWs.

  20. Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea.

    PubMed

    Sendin, Gaston; Bourien, Jérôme; Rassendren, François; Puel, Jean-Luc; Nouvian, Régis

    2014-02-01

    Inner hair cells (IHCs) are the primary transducer for sound encoding in the cochlea. In contrast to the graded receptor potential of adult IHCs, immature hair cells fire spontaneous calcium action potentials during the first postnatal week. This spiking activity has been proposed to shape the tonotopic map along the ascending auditory pathway. Using perforated patch-clamp recordings, we show that developing IHCs fire spontaneous bursts of action potentials and that this pattern is indistinguishable along the basoapical gradient of the developing cochlea. In both apical and basal IHCs, the spiking behavior undergoes developmental changes, where the bursts of action potential tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. Although disruption of purinergic signaling does not interfere with the action potential firing pattern, pharmacological ablation of the α9α10 nicotinic receptor elicits an increase in the discharge rate. We therefore suggest that in addition to carrying place information to the ascending auditory nuclei, the IHCs firing pattern controlled by the α9α10 receptor conveys a temporal signature of the cochlear development. PMID:24429348

  1. Ca channel gating during cardiac action potentials.

    PubMed

    Mazzanti, M; DeFelice, L J

    1990-10-01

    How do Ca channels conduct Ca ions during the cardiac action potential? We attempt to answer this question by applying a two-microelectrode technique, previously used for Na and K currents, in which we record the patch current and the action potential at the same time (Mazzanti, M., and L. J. DeFelice. 1987. Biophys. J. 12:95-100, and 1988. Biophys. J. 54:1139-1148; Wellis, D., L. J. DeFelice, and M. Mazzanti. 1990. Biophys. J. 57:41-48). In this paper, we also compare the action currents obtained by the technique with the step-protocol currents obtained during standard voltage-clamp experiments. Individual Ca channels were measured in 10 mM Ca/1 Ba and 10 mM Ba. To describe part of our results, we use the nomenclature introduced by Hess, P., J. B. Lansman, and R. W. Tsien (1984. Nature (Lond.). 311:538-544). With Ba as the charge carrier, Ca channel kinetics convert rapidly from long to short open times as the patch voltage changes from 20 to -20 mV. This voltage-dependent conversion occurs during action potentials and in step-protocol experiments. With Ca as the charge carrier, the currents are brief at all voltages, and it is difficult to define either the number of channels in the patch or the conductance of the individual channels. Occasionally, however, Ca-conducting channels spontaneously convert to long-open-time kinetics (in Hess et al., 1984, notation, mode 2). When this happens, which is about once in every 100beats, there usually appears to be only one channel in the patch. In this rare configuration, the channel is open long enough to measure its conductance in 10 Ca/ 1 Ba. The value is 8-10 pS, which is about half the conductance in Ba. Because the long openings occur so infrequently with Ca as the charge carrier, they contribute negligibly to the average Ca current at any particular time during an action potential. However, the total number of Ca ions entering during these long openings may be significant when compared to the number entering by the

  2. Spike Sorting Paradigm for Classification of Multi-channel Recorded Fasciculation Potentials

    PubMed Central

    Jahanmiri-Nezhad, Faezeh; Barkhaus, Paul E; Rymer, William Zev; Zhou, Ping

    2014-01-01

    Background Fasciculation potentials (FPs) are important in supporting the electrodiagnosis of Amyotrophic Lateral Sclerosis (ALS). If classified by shape, FPs can also be very informative for laboratory-based neurophysiological investigations of the motor units. Methods This study describes a Matlab program for classification of FPs recorded by multichannel surface electromyogram (EMG) electrodes. The program applies Principal Component Analysis on a set of features recorded from all channels. Then, it registers unsupervised and supervised classification algorithms to sort the FP samples. Qualitative and quantitative evaluation of the results is provided for the operator to assess the outcome. The algorithm facilitates manual interactive modification of the results. Classification accuracy can be improved progressively until the user is satisfied. The program makes no assumptions regarding the occurrence times of the action potentials, in keeping with the rather sporadic and irregular nature of FP firings. Results Ten sets of experimental data recorded from subjects with ALS using a 20-channel surface electrode array were tested. A total of 11891 FPs were detected and classified into a total of 235 prototype template waveforms. Evaluation and correction of classification outcome of such a dataset with over 6000 FPs can be achieved within 1–2 days. Facilitated interactive evaluation and modification could expedite the process of gaining accurate final results. Conclusion The developed Matlab program is an efficient toolbox for classification of FPs. PMID:25450215

  3. Correlates of a single cortical action potential in the epidural EEG

    PubMed Central

    Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel

    2015-01-01

    To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

  4. Synapse-Level Determination of Action Potential Duration by K(+) Channel Clustering in Axons.

    PubMed

    Rowan, Matthew J M; DelCanto, Gina; Yu, Jianqing J; Kamasawa, Naomi; Christie, Jason M

    2016-07-20

    In axons, an action potential (AP) is thought to be broadcast as an unwavering binary pulse over its arbor, driving neurotransmission uniformly at release sites. Yet by recording from axons of cerebellar stellate cell (SC) interneurons, we show that AP width varies between presynaptic bouton sites, even within the same axon branch. The varicose geometry of SC boutons alone does not impose differences in spike duration. Rather, axonal patching revealed heterogeneous peak conductance densities of currents mediated mainly by fast-activating Kv3-type potassium channels, with clustered hotspots at boutons and restricted expression at adjoining shafts. Blockade of Kv channels at individual boutons indicates that currents immediately local to a release site direct spike repolarization at that location. Thus, the clustered arrangement and variable expression density of Kv3 channels at boutons are key determinants underlying compartmentalized control of AP width in a near synapse-by-synapse manner, multiplying the signaling capacity of these structures. PMID:27346528

  5. 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

  6. 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

  7. 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

  8. Developmental changes in the inward current of the action potential of Rohon-Beard neurones

    PubMed Central

    Baccaglini, Paola I.; Spitzer, Nicholas C.

    1977-01-01

    1. Rohon-Beard cells in the spinal cord of Xenopus tadpoles have been studied in animals from early neural tube to free-swimming larval stages. The onset and further development of electrical excitability of these neurones has been investigated in different ionic environments, to determine the ionic species carrying the inward current of the action potential. 2. The cells appear inexcitable at early stages (Nieuwkoop & Faber stages 18-20) and do not give action potentials to depolarizing current pulses. 3. The action potential is first recorded at stage 20. (A) The inward current is carried by Ca2+ at stages 20-25, since it is blocked by mm quantitites of La3+, Co2+ or Mn2+ and is unaffected by removal of Na+ or the addition of tetrodotoxin (TTX). (B) The action potential is an elevated plateau of long duration (mean 190 msec at stages 20-22). The duration decreases exponentially with repetitive stimulation. (C) The specific Ca2+ conductance (gCa) at the onset of the plateau of the action potential is 2·6 × 10-4 mho/cm2. Calculations show that a single action potential raises [Ca2+]1 by more than 100-fold. 4. At later times (stages 25-40), the inward current of the action potential is carried by both Na+ and Ca2+: the action potential has two components, an initial spike which is blocked by removal of Na+ or addition of TTX, followed by a plateau which is blocked by La3+, Co2+ or Mn2+. 5. Finally (stages 40-51), the inward current is primarily carried by Na+, since the action potential is blocked only by removal of Na+ or addition of TTX, and the overshoot agrees with the prediction of the Nernst equation for a Na-selective membrane. When the outward current channel is blocked and cells exposed to Na-free solutions, 67% of cells at the latest stages studied were incapable of producing action potentials in which the inward current is carried by divalent cations. 6. The duration of the action potential decreases from a maximum of about 1000 msec to about 1 msec

  9. Teachers in Action Research: Assumptions and Potentials

    ERIC Educational Resources Information Center

    Li, Yuen-Ling

    2008-01-01

    Research literature has long indicated that action research may stimulate practitioners themselves to actively evaluate the quality of their practice. This study is designed to report the use of action research for the development of early years professional practice by analyzing the pre-project and the post-project video-filmed teaching events.…

  10. Microcomputer program for automated action potential waveform analysis.

    PubMed

    Soto, E; Salceda, E; Cruz, R; Ortega, A; Vega, R

    2000-06-01

    A program for action potential waveform analysis based on a PC compatible computer is described. Single or averaged action potentials are analyzed by obtaining its first derivative and using criteria which allow automatic measurement of several action potential components, including: depolarization rate, repolarization rate, amplitude, duration, resting membrane potential and afterhyperpolarization amplitude and slope. Data can be imported from pClamp (Axon Instruments) and exported to other software such as Excel, Sigmaplot and MatLab for example. PMID:10764940

  11. Decoding 3D reach and grasp from hybrid signals in motor and premotor cortices: spikes, multiunit activity, and local field potentials

    PubMed Central

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

    2012-01-01

    Neural activity in motor cortex during reach and grasp movements shows modulations in a broad range of signals from single-neuron spiking activity (SA) to various frequency bands in broadband local field potentials (LFPs). In particular, spatiotemporal patterns in multiband LFPs are thought to reflect dendritic integration of local and interareal synaptic inputs, attentional and preparatory processes, and multiunit activity (MUA) related to movement representation in the local motor area. Nevertheless, the relationship between multiband LFPs and SA, and their relationship to movement parameters and their relative value as brain-computer interface (BCI) control signals, remain poorly understood. Also, although this broad range of signals may provide complementary information channels in primary (MI) and ventral premotor (PMv) areas, areal differences in information have not been systematically examined. Here, for the first time, the amount of information in SA and multiband LFPs was compared for MI and PMv by recording from dual 96-multielectrode arrays while monkeys made naturalistic reach and grasp actions. Information was assessed as decoding accuracy for 3D arm end point and grip aperture kinematics based on SA or LFPs in MI and PMv, or combinations of signal types across areas. In contrast with previous studies with ≤16 simultaneous electrodes, here ensembles of >16 units (on average) carried more information than multiband, multichannel LFPs. Furthermore, reach and grasp information added by various LFP frequency bands was not independent from that in SA ensembles but rather typically less than and primarily contained within the latter. Notably, MI and PMv did not show a particular bias toward reach or grasp for this task or for a broad range of signal types. For BCIs, our results indicate that neuronal ensemble spiking is the preferred signal for decoding, while LFPs and combined signals from PMv and MI can add robustness to BCI control. PMID:22157115

  12. 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

  13. Robust spike classification based on frequency domain neural waveform features

    NASA Astrophysics Data System (ADS)

    Yang, Chenhui; Yuan, Yuan; Si, Jennie

    2013-12-01

    Objective. We introduce a new spike classification algorithm based on frequency domain features of the spike snippets. The goal for the algorithm is to provide high classification accuracy, low false misclassification, ease of implementation, robustness to signal degradation, and objectivity in classification outcomes. Approach. In this paper, we propose a spike classification algorithm based on frequency domain features (CFDF). It makes use of frequency domain contents of the recorded neural waveforms for spike classification. The self-organizing map (SOM) is used as a tool to determine the cluster number intuitively and directly by viewing the SOM output map. After that, spike classification can be easily performed using clustering algorithms such as the k-Means. Main results. In conjunction with our previously developed multiscale correlation of wavelet coefficient (MCWC) spike detection algorithm, we show that the MCWC and CFDF detection and classification system is robust when tested on several sets of artificial and real neural waveforms. The CFDF is comparable to or outperforms some popular automatic spike classification algorithms with artificial and real neural data. Significance. The detection and classification of neural action potentials or neural spikes is an important step in single-unit-based neuroscientific studies and applications. After the detection of neural snippets potentially containing neural spikes, a robust classification algorithm is applied for the analysis of the snippets to (1) extract similar waveforms into one class for them to be considered coming from one unit, and to (2) remove noise snippets if they do not contain any features of an action potential. Usually, a snippet is a small 2 or 3 ms segment of the recorded waveform, and differences in neural action potentials can be subtle from one unit to another. Therefore, a robust, high performance classification system like the CFDF is necessary. In addition, the proposed algorithm

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. Feedback stabilizes propagation of synchronous spiking in cortical neural networks.

    PubMed

    Moldakarimov, Samat; Bazhenov, Maxim; Sejnowski, Terrence J

    2015-02-24

    Precisely timed action potentials related to stimuli and behavior have been observed in the cerebral cortex. However, information carried by the precise spike timing has to propagate through many cortical areas, and noise could disrupt millisecond precision during the transmission. Previous studies have demonstrated that only strong stimuli that evoke a large number of spikes with small dispersion of spike times can propagate through multilayer networks without degrading the temporal precision. Here we show that feedback projections can increase the number of spikes in spike volleys without degrading their temporal precision. Feedback also increased the range of spike volleys that can propagate through multilayer networks. Our work suggests that feedback projections could be responsible for the reliable propagation of information encoded in spike times through cortex, and thus could serve as an attentional mechanism to regulate the flow of information in the cortex. Feedback projections may also participate in generating spike synchronization that is engaged in cognitive behaviors by the same mechanisms described here for spike propagation. PMID:25675531

  17. 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

  18. 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.

  19. Spike encoding of olfactory receptor cells.

    PubMed

    Narusuye, Kenji; Kawai, Fusao; Miyachi, Ei-ichi

    2003-08-01

    Olfaction begins with the transduction of the information carried by odorants into electrical signals in olfactory receptor cells (ORCs). The binding of odor molecules to specific receptor proteins on the ciliary surface of ORCs induces the receptor potentials. This initial excitation causes a slow and graded depolarizing voltage change, which is encoded into a train of action potentials. Action potentials of ORCs are generated by voltage-gated Na+ currents and T-type Ca2+ currents in the somatic membrane. Isolated ORCs, which have lost their cilia during the dissociation procedure, are known to exhibit spike frequency accommodation by injecting the steady current. This raises the possibility that somatic ionic channels in ORCs may serve for odor adaptation at the level of spike encoding, although odor adaptation is mainly accomplished by the ciliary transduction machinery. This review discusses current knowledge concerning the mechanisms of spike generation in ORCs. It also reviews how neurotransmitters and hormones modulate ionic currents and action potentials in ORCs. PMID:12871762

  20. 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...

  1. 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. PMID:25617615

  2. [Individualised medicine - potentials and need for action].

    PubMed

    Hüsing, Bärbel

    2010-01-01

    Individualised medicine aims to classify seemingly homogenous patient groups into smaller clinically relevant subgroups (stratification) in order to be able to treat them differently, thus contributing to the improvement of health care services, to the prevention of inappropriate treatments and to the reduction of adverse effects. This article summarises a report to the Office of Technology Assessment at the German Bundestag and points out the need for action for transferring individualised medicine from research to clinical application: significant incentives are required in order to prove the clinical validity of newly identified biomarkers of complex diseases. Sustainable business models for the joint development of new applications by research institutions, biotechnology companies, pharmaceuticals and medical devices companies are required. Instruments for transferring knowledge from bench to bedside (translational research) and the existing regulatory framework should be further developed in order to strike an appropriate balance between incentives for accelerating the transfer of innovative technology to the health care sector while, at the same time, ensuring patient safety, high quality and clinical utility. PMID:21147435

  3. Selective effects of an octopus toxin on action potentials

    PubMed Central

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  4. The effects of temperature on human compound action potentials.

    PubMed Central

    Bolton, C F; Sawa, G M; Carter, K

    1981-01-01

    The upper limbs of 10 healthy subjects were cooled and then warmed over physiological temperature ranges. The compound action potentials of median digital nerves, median sensory nerve at the wrist, radial sensory nerve at the wrist, and median thenar muscle, all showed progressive reduction in latency, amplitude, duration and area during rising temperature. Our studies suggest that the sensory compound action potential changes occur predominantly because of the summated effects of reduction in the duration of the action potentials of single myelinated fibres, although disproportionate increase in the conduction velocity of larger myelinated fibres also plays a role. Images PMID:7264687

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

    PubMed Central

    Johnson, Sarah E.; Hudson, John L.

    2015-01-01

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

  6. Intracellular recording of action potentials by nanopillar electroporation

    NASA Astrophysics Data System (ADS)

    Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

    2012-03-01

    Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action

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

    PubMed

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

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems. PMID:26539072

  8. 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

  9. 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...

  10. When less is more: non-monotonic spike sequence processing in neurons.

    PubMed

    Arnoldt, Hinrich; Chang, Shuwen; Jahnke, Sven; Urmersbach, Birk; Taschenberger, Holger; Timme, Marc

    2015-02-01

    Fundamental response properties of neurons centrally underly the computational capabilities of both individual nerve cells and neural networks. Most studies on neuronal input-output relations have focused on continuous-time inputs such as constant or noisy sinusoidal currents. Yet, most neurons communicate via exchanging action potentials (spikes) at discrete times. Here, we systematically analyze the stationary spiking response to regular spiking inputs and reveal that it is generically non-monotonic. Our theoretical analysis shows that the underlying mechanism relies solely on a combination of the discrete nature of the communication by spikes, the capability of locking output to input spikes and limited resources required for spike processing. Numerical simulations of mathematically idealized and biophysically detailed models, as well as neurophysiological experiments confirm and illustrate our theoretical predictions. PMID:25646860

  11. When Less Is More: Non-monotonic Spike Sequence Processing in Neurons

    PubMed Central

    Arnoldt, Hinrich; Chang, Shuwen; Jahnke, Sven; Urmersbach, Birk; Taschenberger, Holger; Timme, Marc

    2015-01-01

    Fundamental response properties of neurons centrally underly the computational capabilities of both individual nerve cells and neural networks. Most studies on neuronal input-output relations have focused on continuous-time inputs such as constant or noisy sinusoidal currents. Yet, most neurons communicate via exchanging action potentials (spikes) at discrete times. Here, we systematically analyze the stationary spiking response to regular spiking inputs and reveal that it is generically non-monotonic. Our theoretical analysis shows that the underlying mechanism relies solely on a combination of the discrete nature of the communication by spikes, the capability of locking output to input spikes and limited resources required for spike processing. Numerical simulations of mathematically idealized and biophysically detailed models, as well as neurophysiological experiments confirm and illustrate our theoretical predictions. PMID:25646860

  12. Distinct temporal spike and local field potential activities in the thalamic parafascicular nucleus of parkinsonian rats during rest and limb movement.

    PubMed

    Wang, Min; Qu, Qingyang; He, Tingting; Li, Min; Song, Zhimin; Chen, Feiyu; Zhang, Xiao; Xie, Jinlu; Geng, Xiwen; Yang, Maoquan; Wang, Xiusong; Lei, Chengdong; Hou, Yabing

    2016-08-25

    Several studies have suggested that the thalamic centromedian-parafascicular (CM/PF or the PF in rodents) is implicated in the pathophysiology of Parkinson's disease (PD). However, inconsistent changes in the neuronal firing rate and pattern have been reported in parkinsonian animals. To investigate the impact of a dopaminergic cell lesion on PF extracellular discharge in behaving rats, the PF neural activities in the spike and local field potential (LFP) were recorded in unilaterally 6-hydroxydopamine- (6-OHDA) lesioned and neurologically intact control rats during rest and limb movement. During rest, the two PF neuronal subtypes was less spontaneously active, with no difference in the spike firing rates between the control and lesioned rats; only the lesioned rats reshaped their spike firing pattern. Furthermore, the simultaneously recorded LFP in the lesioned rats exhibited a significant increase in power at 12-35 and 35-70Hz and a decrease in power at 0.7-12Hz. During the execution of a voluntary movement, two subtypes of PF neurons were identified by a rapid increase in the discharge activity in both the control and lesioned rats. However, dopamine lesioning was associated with a decrease in neuronal spiking fire rate and reshaping in the firing pattern in the PF. The simultaneously recorded LFP activity exhibited a significant increase in power at 12-35Hz and a decrease in power at 0.7-12Hz compared with the control rats. These findings indicate that 6-OHDA induces modifications in PF spike and LFP activities in rats during rest and movement and suggest that PF dysfunction may be an important contributor to the pathophysiology of parkinsonian motor impairment. PMID:27238892

  13. Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel.

    PubMed

    Malysz, J; Richardson, D; Farraway, L; Christen, M O; Huizinga, J D

    1995-10-01

    Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13 - 18% and its amplitude by 50 - 70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 mu M), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5 - 10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel

  14. Relationships among low-frequency local field potentials, spiking activity, and three-dimensional reach and grasp kinematics in primary motor and ventral premotor cortices

    PubMed Central

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

    2011-01-01

    A prominent feature of motor cortex field potentials during movement is a distinctive low-frequency local field potential (lf-LFP) (<4 Hz), referred to as the movement event-related potential (mEP). The lf-LFP appears to be a global signal related to regional synaptic input, but its relationship to nearby output signaled by single unit spiking activity (SUA) or to movement remains to be established. Previous studies comparing information in primary motor cortex (MI) lf-LFPs and SUA in the context of planar reaching tasks concluded that lf-LFPs have more information than spikes about movement. However, the relative performance of these signals was based on a small number of simultaneously recorded channels and units, or for data averaged across sessions, which could miss information of larger-scale spiking populations. Here, we simultaneously recorded LFPs and SUA from two 96-microelectrode arrays implanted in two major motor cortical areas, MI and ventral premotor (PMv), while monkeys freely reached for and grasped objects swinging in front of them. We compared arm end point and grip aperture kinematics′ decoding accuracy for lf-LFP and SUA ensembles. The results show that lf-LFPs provide enough information to reconstruct kinematics in both areas with little difference in decoding performance between MI and PMv. Individual lf-LFP channels often provided more accurate decoding of single kinematic variables than any one single unit. However, the decoding performance of the best single unit among the large population usually exceeded that of the best single lf-LFP channel. Furthermore, ensembles of SUA outperformed the pool of lf-LFP channels, in disagreement with the previously reported superiority of lf-LFP decoding. Decoding results suggest that information in lf-LFPs recorded from intracortical arrays may allow the reconstruction of reach and grasp for real-time neuroprosthetic applications, thus potentially supplementing the ability to decode these same

  15. The Effects of Propofol on Local Field Potential Spectra, Action Potential Firing Rate, and Their Temporal Relationship in Humans and Felines

    PubMed Central

    Hanrahan, Sara J.; Greger, Bradley; Parker, Rebecca A.; Ogura, Takahiro; Obara, Shinju; Egan, Talmage D.; House, Paul A.

    2013-01-01

    Propofol is an intravenous sedative hypnotic, which, acting as a GABAA agonist, results in neocortical inhibition. While propofol has been well studied at the molecular and clinical level, less is known about the effects of propofol at the level of individual neurons and local neocortical networks. We used Utah Electrode Arrays (UEAs) to investigate the effects of propofol anesthesia on action potentials (APs) and local field potentials (LFPs). UEAs were implanted into the neocortex of two humans and three felines. The two human patients and one feline received propofol by bolus injection, while the other two felines received target-controlled infusions. We examined the changes in LFP power spectra and AP firing at different levels of anesthesia. Increased propofol concentration correlated with decreased high-frequency power in LFP spectra and decreased AP firing rates, and the generation of large-amplitude spike-like LFP activity; however, the temporal relationship between APs and LFPs remained relatively consistent at all levels of propofol. The probability that an AP would fire at this local minimum of the LFP increased with propofol administration. The propofol-induced suppression of neocortical network activity allowed LFPs to be dominated by low-frequency spike-like activity, and correlated with sedation and unconsciousness. As the low-frequency spike-like activity increased and the AP–LFP relationship became more predictable firing rate encoding capacity is impaired. This suggests a mechanism for decreased information processing in the neocortex that accounts for propofol-induced unconsciousness. PMID:23576977

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

    PubMed

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

    1982-12-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KC1) 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. PMID:7162535

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

    NASA Astrophysics Data System (ADS)

    Przybylski, Aleksander T.; Stratten, Wilford P.; Syren, Robert M.; Fox, Sidney W.

    1982-12-01

    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.

  18. 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.

  19. Far-field potentials recorded from action potentials and from a tripole in a hemicylindrical volume.

    PubMed

    Jewett, D L; Deupree, D L

    1989-05-01

    There is growing evidence in support of the hypothesis that far-field potentials are recorded when action potentials encounter discontinuities in the surrounding volume. The present study found further support for this hypothesis using two methods of experimentation. The first method recorded potentials when the action potential from an isolated bullfrog sciatic nerve in a hemicylindrical volume (i) encountered a change in the shape of the surrounding volume, (ii) crossed a boundary between 2 volumes of differing resistivities, (iii) reached a bend in the nerve, or (iv) reached the functional end of the nerve. In the second method, potentials were recorded when an electrical tripole, constructed in a way to produce the electrical equivalent of an action potential, encountered the same discontinuities as well as when it was configured to simulate a curved nerve. These results are consistent with the hypothesis that dipole components of an action potential predominant in far-field recordings. PMID:2469568

  20. Inactivation of nucleus incertus impairs passive avoidance learning and long term potentiation of the population spike in the perforant path-dentate gyrus evoked field potentials in rats.

    PubMed

    Nategh, Mohsen; Nikseresht, Sara; Khodagholi, Fariba; Motamedi, Fereshteh

    2016-04-01

    Involvement of brainstem nucleus incertus (NI) in hippocampal theta rhythm suggests that this structure might play a role in hippocampal-dependent learning and memory. In the present study we aimed to address if NI is involved in an avoidance learning task as well as dentate gyrus (DG) short-term and long-term potentiation. Lidocaine was injected into the NI to transiently inactivate the nucleus, and control rats received saline. Role of NI was studied in passive avoidance learning (PAL) in 3 memory phases of acquisition, consolidation and retrieval. Levels of hippocampal phosphorylated p70 were also assessed in rats involved in PAL. Perforant path-DG short-term synaptic plasticity was studied upon NI inactivation before the paired-pulse stimulation, and also before or after tetanic stimulation in freely moving rats. It was found that NI inactivation delayed learning and impaired retention in the PAL task, with decreased levels of phosphorylated p70 in the respective groups. However, short-term plasticity was not affected by NI inactivation. But long term potentiation (LTP) of DG population spike was poorly induced with NI inactivation compared to the saline group, and it had no effect on population excitatory post-synaptic potential. Furthermore, when NI was inactivated after the induction of LTP, there was no difference between the saline and lidocaine groups. These observations suggest that NI has a role in PAL task, and its inactivation does not change the perforant path-DG granule cell synaptic input but decreases the excitability of the DG granule cells. Further studies should elucidate direct and indirect paths through which NI might influence hippocampal activity. PMID:26927304

  1. 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

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

    PubMed

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

    2016-06-01

    Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. PMID:26817404

  3. 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. PMID:26711713

  4. 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

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

    PubMed

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

    2011-09-01

    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 (V(m) 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

  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. 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…

  9. 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. PMID:5505231

  10. Regulation of Action Potential Waveforms by Axonal GABAA Receptors in Cortical Pyramidal Neurons

    PubMed Central

    Xia, Yang; Zhao, Yuan; Yang, Mingpo; Zeng, Shaoqun; Shu, Yousheng

    2014-01-01

    GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb) of the main axon trunk of layer –5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs) and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors. PMID:24971996

  11. 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

  12. Dual Roles for Spike Signaling in Cortical Neural Populations

    PubMed Central

    Ballard, Dana H.; Jehee, Janneke F. M.

    2011-01-01

    A prominent feature of signaling in cortical neurons is that of randomness in the action potential. The output of a typical pyramidal cell can be well fit with a Poisson model, and variations in the Poisson rate repeatedly have been shown to be correlated with stimuli. However while the rate provides a very useful characterization of neural spike data, it may not be the most fundamental description of the signaling code. Recent data showing γ frequency range multi-cell action potential correlations, together with spike timing dependent plasticity, are spurring a re-examination of the classical model, since precise timing codes imply that the generation of spikes is essentially deterministic. Could the observed Poisson randomness and timing determinism reflect two separate modes of communication, or do they somehow derive from a single process? We investigate in a timing-based model whether the apparent incompatibility between these probabilistic and deterministic observations may be resolved by examining how spikes could be used in the underlying neural circuits. The crucial component of this model draws on dual roles for spike signaling. In learning receptive fields from ensembles of inputs, spikes need to behave probabilistically, whereas for fast signaling of individual stimuli, the spikes need to behave deterministically. Our simulations show that this combination is possible if deterministic signals using γ latency coding are probabilistically routed through different members of a cortical cell population at different times. This model exhibits standard features characteristic of Poisson models such as orientation tuning and exponential interval histograms. In addition, it makes testable predictions that follow from the γ latency coding. PMID:21687798

  13. Effects of Odor Stimulation on Antidromic Spikes in Olfactory Sensory Neurons

    PubMed Central

    Scott, John W.; Sherrill, Lisa

    2008-01-01

    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

  14. 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

  15. Spike timing and visual processing in the retinogeniculocortical pathway.

    PubMed Central

    Usrey, W Martin

    2002-01-01

    Although the visual response properties of neurons along the retinogeniculocortical pathway have been studied for decades, relatively few studies have examined how individual neurons along the pathway communicate with each other. Recent studies in the cat (Felis domestica) now show that the strength of these connections is very dynamic and spike timing plays an important part in determining whether action potentials will be transferred from pre- to postsynaptic cells. This review explores recent progress in our understanding of what role spike timing has in establishing different patterns of geniculate activity and how these patterns ultimately drive the cortex. PMID:12626007

  16. Spike Inference from Calcium Imaging Using Sequential Monte Carlo Methods

    PubMed Central

    Vogelstein, Joshua T.; Watson, Brendon O.; Packer, Adam M.; Yuste, Rafael; Jedynak, Bruno; Paninski, Liam

    2009-01-01

    Abstract As recent advances in calcium sensing technologies facilitate simultaneously imaging action potentials in neuronal populations, complementary analytical tools must also be developed to maximize the utility of this experimental paradigm. Although the observations here are fluorescence movies, the signals of interest—spike trains and/or time varying intracellular calcium concentrations—are hidden. Inferring these hidden signals is often problematic due to noise, nonlinearities, slow imaging rate, and unknown biophysical parameters. We overcome these difficulties by developing sequential Monte Carlo methods (particle filters) based on biophysical models of spiking, calcium dynamics, and fluorescence. We show that even in simple cases, the particle filters outperform the optimal linear (i.e., Wiener) filter, both by obtaining better estimates and by providing error bars. We then relax a number of our model assumptions to incorporate nonlinear saturation of the fluorescence signal, as well external stimulus and spike history dependence (e.g., refractoriness) of the spike trains. Using both simulations and in vitro fluorescence observations, we demonstrate temporal superresolution by inferring when within a frame each spike occurs. Furthermore, the model parameters may be estimated using expectation maximization with only a very limited amount of data (e.g., ∼5–10 s or 5–40 spikes), without the requirement of any simultaneous electrophysiology or imaging experiments. PMID:19619479

  17. 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

  18. Relationship between action potential, contraction-relaxation pattern, and intracellular Ca2+ transient in cardiomyocytes of dogs with chronic heart failure.

    PubMed

    Maltsev, V A; Sabbah, H N; Tanimura, M; Lesch, M; Goldstein, S; Undrovinas, A I

    1998-06-01

    Abnormalities of contractile function have been identified in cardiomyocytes isolated from failed human hearts and from hearts of animals with experimentally induced heart failure (HF). The mechanism(s) responsible for these functional abnormalities are not fully understood. In the present study, we examined the relationship between action potential duration, pattern of contraction and relaxation, and associated intracellular Ca2+ transients in single cardiomyocytes isolated from the left ventricle (LV) of dogs (n = 7) with HF produced by multiple sequential intracoronary microembolizations. Comparisons were made with LV cardiomyocytes isolated from normal dogs. Action potentials were measured in isolated LV cardiomyocytes by perforated patch clamp, Ca2+ transients by fluo 3 probe fluorescence, and cardiomyocyte contraction and relaxation by edge movement detector. HF cardiomyocytes exhibited an abnormal pattern of contraction and relaxation characterized by an attenuated initial twitch (spike) followed by a sustained contracture ('dome') of 1 to 8 s in duration and subsequent delayed relaxation. This pattern was more prominent at low stimulation rates (58% at 0.2 Hz, n = 211, 21% at 0.5 Hz, n = 185). Measurements of Ca2+ transients in HF cardiomyocytes at 0.2 Hz manifested a similar spike and dome configuration. The dome phase of both the contraction/relaxation pattern and Ca2+ transients seen in HF cardiomyocytes coincided with a sustained plateau of the action potential. Shortening of the action potential duration by administration of saxitoxin (100 nM) or lidocaine (30 microM) reduced the duration of the dome phase of both the contraction/relaxation profile as well as that of the Ca2+ transient profile. An increase of stimulation rate up to 1 Hz caused shortening of the action potential and disappearance of the spike-dome profile in the majority of HF cardiomyocytes. In HF cardiomyocytes, the action potential and Ca2+ transient duration were not significantly

  19. Action potentials of curved nerves in finite limbs.

    PubMed

    Xiao, S; McGill, K C; Hentz, V R

    1995-06-01

    Previous simulations of volume-conducted nerve-fiber action-potentials have modeled the limb as semi-infinite or circularly cylindrical, and the fibers as straight lines parallel to the limb surface. The geometry of actual nerves and limbs, however, can be considerably more complicated. This paper presents a general method for computing the potentials of fibers with arbitrary paths in arbitrary finite limbs. It involves computing the propagating point-source response (PPSR), which is the potential arising from a single point source (dipole or tripole) travelling along the fiber. The PPSR can be applied to fibers of different conduction velocities by simple dilation or compression. The method is illustrated for oblique and spiralling nerve fibers. Potentials from oblique fibers are shown to be different for orthodromic and antidromic propagation. Such results show that the straight-line models are not always adequate for nerves with anatomical amounts of curvature. PMID:7790016

  20. Wavelet analysis of epileptic spikes

    NASA Astrophysics Data System (ADS)

    Latka, Miroslaw; Was, Ziemowit; Kozik, Andrzej; West, Bruce J.

    2003-05-01

    Interictal spikes and sharp waves in human EEG are characteristic signatures of epilepsy. These potentials originate as a result of synchronous pathological discharge of many neurons. The reliable detection of such potentials has been the long standing problem in EEG analysis, especially after long-term monitoring became common in investigation of epileptic patients. The traditional definition of a spike is based on its amplitude, duration, sharpness, and emergence from its background. However, spike detection systems built solely around this definition are not reliable due to the presence of numerous transients and artifacts. We use wavelet transform to analyze the properties of EEG manifestations of epilepsy. We demonstrate that the behavior of wavelet transform of epileptic spikes across scales can constitute the foundation of a relatively simple yet effective detection algorithm.

  1. Spike Sorting by Joint Probabilistic Modeling of Neural Spike Trains and Waveforms

    PubMed Central

    Matthews, Brett A.; Clements, Mark A.

    2014-01-01

    This paper details a novel probabilistic method for automatic neural spike sorting which uses stochastic point process models of neural spike trains and parameterized action potential waveforms. A novel likelihood model for observed firing times as the aggregation of hidden neural spike trains is derived, as well as an iterative procedure for clustering the data and finding the parameters that maximize the likelihood. The method is executed and evaluated on both a fully labeled semiartificial dataset and a partially labeled real dataset of extracellular electric traces from rat hippocampus. In conditions of relatively high difficulty (i.e., with additive noise and with similar action potential waveform shapes for distinct neurons) the method achieves significant improvements in clustering performance over a baseline waveform-only Gaussian mixture model (GMM) clustering on the semiartificial set (1.98% reduction in error rate) and outperforms both the GMM and a state-of-the-art method on the real dataset (5.04% reduction in false positive + false negative errors). Finally, an empirical study of two free parameters for our method is performed on the semiartificial dataset. PMID:24829568

  2. Energy demands of diverse spiking cells from the neocortex, hippocampus, and thalamus

    PubMed Central

    Moujahid, Abdelmalik; D'Anjou, Alicia; Graña, Manuel

    2014-01-01

    It has long been known that neurons in the brain are not physiologically homogeneous. In response to current stimulus, they can fire several distinct patterns of action potentials that are associated with different physiological classes ranging from regular-spiking cells, fast-spiking cells, intrinsically bursting cells, and low-threshold cells. In this work we show that the high degree of variability in firing characteristics of action potentials among these cells is accompanied with a significant variability in the energy demands required to restore the concentration gradients after an action potential. The values of the metabolic energy were calculated for a wide range of cell temperatures and stimulus intensities following two different approaches. The first one is based on the amount of Na+ load crossing the membrane during a single action potential, while the second one focuses on the electrochemical energy functions deduced from the dynamics of the computational neuron models. The results show that the thalamocortical relay neuron is the most energy-efficient cell consuming between 7 and 18 nJ/cm2 for each spike generated, while both the regular and fast spiking cells from somatosensory cortex and the intrinsically-bursting cell from a cat visual cortex are the least energy-efficient, and can consume up to 100 nJ/cm2 per spike. The lowest values of these energy demands were achieved at higher temperatures and high external stimuli. PMID:24782749

  3. 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

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

    PubMed

    Golovko, Vladimir; Gonotkov, Mikhail; Lebedeva, Elena

    2015-07-01

    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

  5. 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.

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

    PubMed

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

    2016-03-18

    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. PMID:26871752

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

    PubMed

    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

  8. 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. PMID:23422156

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

    PubMed

    Teka, Wondimu; Stockton, David; Santamaria, Fidel

    2016-03-01

    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

  10. 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

  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. PMID:26458902

  12. The bioelectrical source in computing single muscle fiber action potentials.

    PubMed Central

    van Veen, B K; Wolters, H; Wallinga, W; Rutten, W L; Boom, H B

    1993-01-01

    Generally, single muscle fiber action potentials (SFAPs) are modeled as a convolution of the bioelectrical source (being the transmembrane current) with a weighting or transfer function, representing the electrical volume conduction. In practice, the intracellular action potential (IAP) rather than the transmembrane current is often used as the source, because the IAP is relatively easy to obtain under experimental conditions. Using a core conductor assumption, the transmembrane current equals the second derivative of the IAP. In previous articles, discrepancies were found between experimental and simulated SFAPs. Adaptations in the volume conductor slightly altered the simulation results. Another origin of discrepancy might be an erroneous description of the source. Therefore, in the present article, different sources were studied. First, an analytical description of the IAP was used. Furthermore, an experimental IAP, a special experimental SFAP, and a measured transmembrane current scaled to our experimental situation were applied. The results for the experimental IAP were comparable to those with the analytical IAP. The best agreement between experimental and simulated data was found for a measured transmembrane current as source, but differences are still apparent. PMID:8324186

  13. 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

  14. 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.

  15. 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. PMID:21117748

  16. Metabolic syndrome potentiates the cardiac action potential-prolonging action of drugs: a possible 'anti-proarrhythmic' role for amlodipine.

    PubMed

    Caillier, Bertrand; Pilote, Sylvie; Patoine, Dany; Levac, Xavier; Couture, Christian; Daleau, Pascal; Simard, Chantale; Drolet, Benoit

    2012-03-01

    Type II diabetes was shown to prolong the QT interval on the ECG and to promote cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor state of type II diabetes. The objectives of the present study were to generate a guinea pig model of metabolic syndrome by long-term exposure to diabetogenic diets, and to evaluate the monophasic action potential duration (MAPD)-modulating effects of drugs in these animals. Male Hartley guinea pigs were fed with either the control, the High Fat High Sucrose (HFHS) or the High Fat High Fructose (HFHF) diet for 150 days. Evolution of weight, blood cholesterol, triglycerides, urea and glucose tolerance were regularly monitored. Histopathological evolution was also evaluated in target organs such as pancreas, heart, liver and kidneys. Ex vivo experiments using the Langendorff retroperfusion technique, isolated hearts from guinea pigs either fed with the control, the HFHS or the HFHF diet were exposed to dofetilide 20 nM (D), chromanol 293B 10 μM (C) and amlodipine 100 nM (A) in different drug combinations and monophasic action potential duration was measured at 90% repolarization (MAPD₉₀). Our data show that it is possible to generate a guinea pig model of metabolic syndrome by chronic exposure to diabetogenic diets. Minor histopathological abnormalities were observed, mainly in the pancreas and the liver. Metabolic syndrome potentiates the MAPD-prolonging actions of I(Kr)-blocking (dofetilide) and I(Ks)-blocking (chromanol 293B) drugs, an effect that is reversible upon administration of the calcium channel blocker amlodipine. PMID:22154802

  17. 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. PMID:27288809

  18. 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.

  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. Cardiac dynamics: a simplified model for action potential propagation

    PubMed Central

    2012-01-01

    This paper analyzes a new semiphysiological ionic model, used recently to study reexitations and reentry in cardiac tissue [I.R. Cantalapiedra et al, PRE 82 011907 (2010)]. The aim of the model is to reproduce action potencial morphologies and restitution curves obtained, either from experimental data, or from more complex electrophysiological models. The model divides all ion currents into four groups according to their function, thus resulting into fast-slow and inward-outward currents. We show that this simplified model is flexible enough as to accurately capture the electrical properties of cardiac myocytes, having the advantage of being less computational demanding than detailed electrophysiological models. Under some conditions, it has been shown to be amenable to mathematical analysis. The model reproduces the action potential (AP) change with stimulation rate observed both experimentally and in realistic models of healthy human and guinea pig myocytes (TNNP and LRd models, respectively). When simulated in a cable it also gives the right dependence of the conduction velocity (CV) with stimulation rate. Besides reproducing correctly these restitution properties, it also gives a good fit for the morphology of the AP, including the notch typical of phase 1. Finally, we perform simulations in a realistic geometric model of the rabbit’s ventricles, finding a good qualitative agreement in AP propagation and the ECG. Thus, this simplified model represents an alternative to more complex models when studying instabilities in wave propagation. PMID:23194429

  1. Simulation analysis of effects of adrenaline on spike generation in olfactory receptor cells.

    PubMed

    Kawai, F

    1999-12-01

    Adrenaline is known to affect action potentials induced by the step current injection in an olfactory receptor cell (ORC). It is unclear, however, whether it also modulates action potentials induced by odor stimuli. In the present study, the effects of adrenaline on action potentials in ORCs were investigated quantitatively using a computer simulation. Adrenaline suppressed simulated action potentials induced by step current injection near threshold, and increased spike frequency to strong stimuli by 8-25%. Similar effects were obtained by applying a pseudo-transduction current to a model cell. Surprisingly, adrenaline markedly increased spike frequency to strong stimuli by 30-140%, and increased the slope of the stimulus-response relation compared with that of the step current injection. This suggests that adrenaline enhances odorant contrast in olfactory perception by modulating signal encoding of ORCs. PMID:10587504

  2. Dipole characterization of single neurons from their extracellular action potentials

    PubMed Central

    Victor, Jonathan D.

    2011-01-01

    The spatial variation of the extracellular action potentials (EAP) of a single neuron contains information about the size and location of the dominant current source of its action potential generator, which is typically in the vicinity of the soma. Using this dependence in reverse in a three-component realistic probe + brain + source model, we solved the inverse problem of characterizing the equivalent current source of an isolated neuron from the EAP data sampled by an extracellular probe at multiple independent recording locations. We used a dipole for the model source because there is extensive evidence it accurately captures the spatial roll-off of the EAP amplitude, and because, as we show, dipole localization, beyond a minimum cell-probe distance, is a more accurate alternative to approaches based on monopole source models. Dipole characterization is separable into a linear dipole moment optimization where the dipole location is fixed, and a second, nonlinear, global optimization of the source location. We solved the linear optimization on a discrete grid via the lead fields of the probe, which can be calculated for any realistic probe + brain model by the finite element method. The global source location was optimized by means of Tikhonov regularization that jointly minimizes model error and dipole size. The particular strategy chosen reflects the fact that the dipole model is used in the near field, in contrast to the typical prior applications of dipole models to EKG and EEG source analysis. We applied dipole localization to data collected with stepped tetrodes whose detailed geometry was measured via scanning electron microscopy. The optimal dipole could account for 96% of the power in the spatial variation of the EAP amplitude. Among various model error contributions to the residual, we address especially the error in probe geometry, and the extent to which it biases estimates of dipole parameters. This dipole characterization method can be applied to

  3. Evaluation of a neurotherapy program for a child with ADHD with Benign Partial Epilepsy with Rolandic Spikes (BPERS) using event-related potentials

    PubMed Central

    Pąchalska, Maria; Kropotov, Iurii D.; Mańko, Grzegorz; Lipowska, Małgorzata; Rasmus, Anna; Łukaszewska, Beata; Bogdanowicz, Marta; Mirski, Andrzej

    2012-01-01

    Summary Background We hypothesized that there would be a good response to relative beta training, applied to regulate the dynamics of brain function in a patient with benign partial epilepsy with Rolandic Spikes (BPERS), associated with neuropsychiatric deficits resembling the symptoms of attention deficit-hyperactivity disorder (ADHD). Case Report The patient, E.Z., age 9.3, was suffering from neuropsychiatric symptoms, cognitive dysfunction, especially attention deficits, and behavioral changes, rendering him unable to function independently in school and in many situations of everyday life. He was treated for epilepsy, but only slight progress was made. The patient took part in 20 sessions of relative beta training combined with behavioral training. We used standardized neuropsychological testing, as well as ERPs before the experiment and after the completion of the neurotherapy program. Neuropsychological testing at baseline showed multiple cognitive deficits. Over the course of neurotherapy, E.Z.’s verbal and non-verbal IQ increased significantly. His cognitive functions also improved, including immediate and delayed logical and visual recall on the WMS-III, maintaining attention on the WMS-III, and executive functions, but remained below norms. Physiologically, the patient showed substantial changes after neurotherapy, including fewer spikes and an increased P300 NOGO component. Conclusions The cognitive deficits characteristic for ADHD in a child with BPERS may be unresponsive to antiepileptic treatment, but are reversible after a carefully selected neurotherapy program, combined with antiepileptic treatment. Event Related Potentials (ERPs) in the GO/NOGO task can be used to assess functional brain changes induced by neurotherapeutical programs. PMID:23111748

  4. The electromagnetic spike solutions

    NASA Astrophysics Data System (ADS)

    Nungesser, Ernesto; Lim, Woei Chet

    2013-12-01

    The aim of this paper is to use the existing relation between polarized electromagnetic Gowdy spacetimes and vacuum Gowdy spacetimes to find explicit solutions for electromagnetic spikes by a procedure which has been developed by one of the authors for gravitational spikes. We present new inhomogeneous solutions which we call the EME and MEM electromagnetic spike solutions.

  5. Influence of developmental nicotine exposure on spike-timing precision and reliability in hypoglossal motoneurons.

    PubMed

    Powell, Gregory L; Levine, Richard B; Frazier, Amanda M; Fregosi, Ralph F

    2015-03-15

    Smoothly graded muscle contractions depend in part on the precision and reliability of motoneuron action potential generation. Whether or not a motoneuron generates spikes precisely and reliably depends on both its intrinsic membrane properties and the nature of the synaptic input that it receives. Factors that perturb neuronal intrinsic properties and/or synaptic drive may compromise the temporal precision and the reliability of action potential generation. We have previously shown that developmental nicotine exposure (DNE) alters intrinsic properties and synaptic transmission in hypoglossal motoneurons (XIIMNs). Here we show that the effects of DNE also include alterations in spike-timing precision and reliability, and spike-frequency adaptation, in response to sinusoidal current injection. Current-clamp experiments in brainstem slices from neonatal rats show that DNE lowers the threshold for spike generation but increases the variability of spike-timing mechanisms. DNE is also associated with an increase in spike-frequency adaptation and reductions in both peak and steady-state firing rate in response to brief, square wave current injections. Taken together, our data indicate that DNE causes significant alterations in the input-output efficiency of XIIMNs. These alterations may play a role in the increased frequency of obstructive apneas and altered suckling strength and coordination observed in nicotine-exposed neonatal humans. PMID:25552642

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

    PubMed Central

    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. PMID:26074810

  7. 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

  8. HCN channels enhance spike phase coherence and regulate the phase of spikes and LFPs in the theta-frequency range.

    PubMed

    Sinha, Manisha; Narayanan, Rishikesh

    2015-04-28

    What are the implications for the existence of subthreshold ion channels, their localization profiles, and plasticity on local field potentials (LFPs)? Here, we assessed the role of hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in altering hippocampal theta-frequency LFPs and the associated spike phase. We presented spatiotemporally randomized, balanced theta-modulated excitatory and inhibitory inputs to somatically aligned, morphologically realistic pyramidal neuron models spread across a cylindrical neuropil. We computed LFPs from seven electrode sites and found that the insertion of an experimentally constrained HCN-conductance gradient into these neurons introduced a location-dependent lead in the LFP phase without significantly altering its amplitude. Further, neurons fired action potentials at a specific theta phase of the LFP, and the insertion of HCN channels introduced large lags in this spike phase and a striking enhancement in neuronal spike-phase coherence. Importantly, graded changes in either HCN conductance or its half-maximal activation voltage resulted in graded changes in LFP and spike phases. Our conclusions on the impact of HCN channels on LFPs and spike phase were invariant to changes in neuropil size, to morphological heterogeneity, to excitatory or inhibitory synaptic scaling, and to shifts in the onset phase of inhibitory inputs. Finally, we selectively abolished the inductive lead in the impedance phase introduced by HCN channels without altering neuronal excitability and found that this inductive phase lead contributed significantly to changes in LFP and spike phase. Our results uncover specific roles for HCN channels and their plasticity in phase-coding schemas and in the formation and dynamic reconfiguration of neuronal cell assemblies. PMID:25870302

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

    PubMed Central

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

    2010-01-01

    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. PMID:20212117

  10. Dendritic spikes enhance stimulus selectivity in cortical neurons in vivo.

    PubMed

    Smith, Spencer L; Smith, Ikuko T; Branco, Tiago; Häusser, Michael

    2013-11-01

    Neuronal dendrites are electrically excitable: they can generate regenerative events such as dendritic spikes in response to sufficiently strong synaptic input. Although such events have been observed in many neuronal types, it is not well understood how active dendrites contribute to the tuning of neuronal output in vivo. Here we show that dendritic spikes increase the selectivity of neuronal responses to the orientation of a visual stimulus (orientation tuning). We performed direct patch-clamp recordings from the dendrites of pyramidal neurons in the primary visual cortex of lightly anaesthetized and awake mice, during sensory processing. Visual stimulation triggered regenerative local dendritic spikes that were distinct from back-propagating action potentials. These events were orientation tuned and were suppressed by either hyperpolarization of membrane potential or intracellular blockade of NMDA (N-methyl-d-aspartate) receptors. Both of these manipulations also decreased the selectivity of subthreshold orientation tuning measured at the soma, thus linking dendritic regenerative events to somatic orientation tuning. Together, our results suggest that dendritic spikes that are triggered by visual input contribute to a fundamental cortical computation: enhancing orientation selectivity in the visual cortex. Thus, dendritic excitability is an essential component of behaviourally relevant computations in neurons. PMID:24162850

  11. 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.

  12. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    NASA Astrophysics Data System (ADS)

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  13. Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment.

    PubMed

    Feron, V J; Til, H P; de Vrijer, F; Woutersen, R A; Cassee, F R; van Bladeren, P J

    1991-01-01

    Aldehydes constitute a group of relatively reactive organic compounds. They occur as natural (flavoring) constituents in a wide variety of foods and food components, often in relatively small, but occasionally in very large concentrations, and are also widely used as food additives. Evidence of carcinogenic potential in experimental animals is convincing for formaldehyde and acetaldehyde, limited for crotonaldehyde, furfural and glycidaldehyde, doubtful for malondialdehyde, very weak for acrolein and absent for vanillin. Formaldehyde carcinogenesis is a high-dose phenomenon in which the cytotoxicity plays a crucial role. Cytotoxicity may also be of major importance in acetaldehyde carcinogenesis but further studies are needed to prove or disprove this assumption. For a large number of aldehydes (relevant) data on neither carcinogenicity nor genotoxicity are available. From epidemiological studies there is no convincing evidence of aldehyde exposure being related to cancer in humans. Overall assessment of the cancer risk of aldehydes in the diet leads to the conclusion that formaldehyde, acrolein, citral and vanillin are no dietary risk factors, and that the opposite may be true for acetaldehyde, crotonaldehyde and furfural. Malondialdehyde, glycidaldehyde, benzaldehyde, cinnamaldehyde and anisaldehyde cannot be evaluated on the basis of the available data. A series of aldehydes should be subjected to at least mutagenicity, cytogenicity and cytotoxicity tests. Priority setting for testing should be based on expected mechanism of action and degree of human exposure. PMID:2017217

  14. Pharmacological actions of statins: potential utility in COPD.

    PubMed

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

  15. Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity

    PubMed Central

    Carlisle, Holly J; Fink, Ann E; Grant, Seth G N; O'Dell, Thomas J

    2008-01-01

    The membrane-associated guanylate kinases (MAGUKs) PSD-95, PSD-93 and SAP102 are thought to have crucial roles in both AMPA receptor trafficking and formation of NMDA receptor-associated signalling complexes involved in synaptic plasticity. While PSD-95, PSD-93, and SAP102 appear to have similar roles in AMPA receptor trafficking, it is not known whether these MAGUKs also have functionally similar roles in synaptic plasticity. To explore this issue we examined several properties of basal synaptic transmission in the hippocampal CA1 region of PSD-93 and PSD-95 mutant mice and compared the ability of a number of different synaptic stimulation protocols to induce long-term potentiation (LTP) and long-term depression (LTD) in these mutants. We find that while both AMPA and NMDA receptor-mediated synaptic transmission are normal in PSD-93 mutants, PSD-95 mutant mice exhibit clear deficits in AMPA receptor-mediated transmission. Moreover, in contrast to the facilitation of LTP induction and disruption of LTD observed in PSD-95 mutant mice, PSD-93 mutant mice exhibit deficits in LTP and normal LTD. Our results suggest that PSD-95 has a unique role in AMPA receptor trafficking at excitatory synapses in the hippocampus of adult mice and indicate that PSD-93 and PSD-95 have essentially opposite roles in LTP, perhaps because these MAGUKs form distinct NMDA receptor signalling complexes that differentially regulate the induction of LTP by different patterns of synaptic activity. PMID:18936077

  16. Contribution of auditory nerve fibers to compound action potential of the auditory nerve.

    PubMed

    Bourien, Jérôme; Tang, Yong; Batrel, Charlène; Huet, Antoine; Lenoir, Marc; Ladrech, Sabine; Desmadryl, Gilles; Nouvian, Régis; Puel, Jean-Luc; Wang, Jing

    2014-09-01

    Sound-evoked compound action potential (CAP), which captures the synchronous activation of the auditory nerve fibers (ANFs), is commonly used to probe deafness in experimental and clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low sound pressure levels activate the high-spontaneous rate (SR) fibers, and increasing levels gradually recruit medium- and then low-SR fibers. In this study, we quantitatively analyze the contribution of the ANFs to CAP 6 days after 30-min infusion of ouabain into the round window niche. Anatomic examination showed a progressive ablation of ANFs following increasing concentration of ouabain. CAP amplitude and threshold plotted against loss of ANFs revealed three ANF pools: 1) a highly ouabain-sensitive pool, which does not participate in either CAP threshold or amplitude, 2) a less sensitive pool, which only encoded CAP amplitude, and 3) a ouabain-resistant pool, required for CAP threshold and amplitude. Remarkably, distribution of the three pools was similar to the SR-based ANF distribution (low-, medium-, and high-SR fibers), suggesting that the low-SR fiber loss leaves the CAP unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis and further showed that it is due to the delayed and broad first spike latency distribution of low-SR fibers. In addition to unraveling the neural mechanisms that encode CAP, our computational simulation of an assembly of guinea pig ANFs generalizes and extends our experimental findings to different species of mammals. Altogether, our data demonstrate that substantial ANF loss can coexist with normal hearing threshold and even unchanged CAP amplitude. PMID:24848461

  17. 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

  18. Intracellular Calcium Spikes in Rat Suprachiasmatic Nucleus Neurons Induced by BAPTA-Based Calcium Dyes

    PubMed Central

    Hong, Jin Hee; Min, Cheol Hong; Jeong, Byeongha; Kojiya, Tomoyoshi; Morioka, Eri; Nagai, Takeharu; Ikeda, Masayuki; Lee, Kyoung J.

    2010-01-01

    Background Circadian rhythms in spontaneous action potential (AP) firing frequencies and in cytosolic free calcium concentrations have been reported for mammalian circadian pacemaker neurons located within the hypothalamic suprachiasmatic nucleus (SCN). Also reported is the existence of “Ca2+ spikes” (i.e., [Ca2+]c transients having a bandwidth of 10∼100 seconds) in SCN neurons, but it is unclear if these SCN Ca2+ spikes are related to the slow circadian rhythms. Methodology/Principal Findings We addressed this issue based on a Ca2+ indicator dye (fluo-4) and a protein Ca2+ sensor (yellow cameleon). Using fluo-4 AM dye, we found spontaneous Ca2+ spikes in 18% of rat SCN cells in acute brain slices, but the Ca2+ spiking frequencies showed no day/night variation. We repeated the same experiments with rat (and mouse) SCN slice cultures that expressed yellow cameleon genes for a number of different circadian phases and, surprisingly, spontaneous Ca2+ spike was barely observed (<3%). When fluo-4 AM or BAPTA-AM was loaded in addition to the cameleon-expressing SCN cultures, however, the number of cells exhibiting Ca2+ spikes was increased to 13∼14%. Conclusions/Significance Despite our extensive set of experiments, no evidence of a circadian rhythm was found in the spontaneous Ca2+ spiking activity of SCN. Furthermore, our study strongly suggests that the spontaneous Ca2+ spiking activity is caused by the Ca2+ chelating effect of the BAPTA-based fluo-4 dye. Therefore, this induced activity seems irrelevant to the intrinsic circadian rhythm of [Ca2+]c in SCN neurons. The problems with BAPTA based dyes are widely known and our study provides a clear case for concern, in particular, for SCN Ca2+ spikes. On the other hand, our study neither invalidates the use of these dyes as a whole, nor undermines the potential role of SCN Ca2+ spikes in the function of SCN. PMID:20224788

  19. Comparison of auditory event-related potentials between children with benign childhood epilepsy with centrotemporal spikes and children with temporal lobe epilepsy.

    PubMed

    Casali, Raquel Leme; Amaral, Maria Isabel Ramos do; Boscariol, Mirela; Lunardi, Luciane Lorencetti; Guerreiro, Marilisa Mantovani; Matas, Carla Gentile; Colella-Santos, Maria Francisca

    2016-06-01

    The abnormal brain discharges observed in benign childhood epilepsy with centrotemporal spikes (BECTS) and temporal lobe epilepsy (TLE) are located close to areas responsible for auditory and language processing. This study aimed to analyze the results of auditory event-related potentials (P300) in children with BECTS and TLE in order to assess whether the epileptic activity in centrotemporal and temporal regions may compromise the integrity and physiology of auditory system structures. This was a prospective, comparative, and cross-sectional study. Group I (GI) consisted of 13 children diagnosed with BECTS, group II (GII), 7 children diagnosed with TLE, and control group (GIII), 16 healthy children, with no hearing or academic complaints. After neurological and basic audiological assessments, P300 was applied. The P300 latency and amplitude were compared between groups. Regarding latency, GI showed 324.1 (+31.5) ms, GII 336.3 (+23.5) ms, and GIII 318 (+27.7) ms. Amplitudes were 4.80 (+3.2) μV in GI, 4.7 (+2.5) μV in GII, and 5.8 (+2.4) μV in GIII. Although children with BECTS showed prolonged latencies and reduced amplitudes, these differences were not considered statistically significant. Children with TLE showed statistically significant prolonged P300 latency compared with the control group (P=0.037). We speculate that abnormal electrical discharges in centrotemporal and temporal regions led to the slowing of auditory processing in our sample. PMID:27131051

  20. 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. PMID:19560491

  1. Monitoring spike train synchrony.

    PubMed

    Kreuz, Thomas; Chicharro, Daniel; Houghton, Conor; Andrzejak, Ralph G; Mormann, Florian

    2013-03-01

    Recently, the SPIKE-distance has been proposed as a parameter-free and timescale-independent measure of spike train synchrony. This measure is time resolved since it relies on instantaneous estimates of spike train dissimilarity. However, its original definition led to spuriously high instantaneous values for eventlike firing patterns. Here we present a substantial improvement of this measure that eliminates this shortcoming. The reliability gained allows us to track changes in instantaneous clustering, i.e., time-localized patterns of (dis)similarity among multiple spike trains. Additional new features include selective and triggered temporal averaging as well as the instantaneous comparison of spike train groups. In a second step, a causal SPIKE-distance is defined such that the instantaneous values of dissimilarity rely on past information only so that time-resolved spike train synchrony can be estimated in real time. We demonstrate that these methods are capable of extracting valuable information from field data by monitoring the synchrony between neuronal spike trains during an epileptic seizure. Finally, the applicability of both the regular and the real-time SPIKE-distance to continuous data is illustrated on model electroencephalographic (EEG) recordings. PMID:23221419

  2. 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

  3. 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

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

    PubMed Central

    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. PMID:25258490

  5. 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

  6. 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,…

  7. 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.

  8. Paraoxon suppresses Ca(2+) spike and afterhyperpolarization in snail neurons: Relevance to the hyperexcitability induction.

    PubMed

    Vatanparast, Jafar; Janahmadi, Mahyar; Asgari, Ali Reza; Sepehri, Houri; Haeri-Rohani, Ali

    2006-04-14

    The effects of organophosphate (OP) paraoxon, active metabolite of parathion, were studied on the Ca(2+) and Ba(2+) spikes and on the excitability of the neuronal soma membranes of land snail (Caucasotachea atrolabiata). Paraoxon (0.3 muM) reversibly decreased the duration and amplitude of Ca(2+) and Ba(2+) spikes. It also reduced the duration and the amplitude of the afterhyperpolarization (AHP) that follows spikes, leading to a significant increase in the frequency of Ca(2+) spikes. Pretreatment with atropine and hexamethonium, selective blockers of muscarinic and nicotinic receptors, respectively, did not prevent the effects of paraoxon on Ca(2+) spikes. Intracellular injection of the calcium chelator BAPTA dramatically decreased the duration and amplitude of AHP and increased the duration and frequency of Ca(2+) spikes. In the presence of BAPTA, paraoxon decreased the duration of the Ca(2+) spikes without affecting their frequency. Apamin, a neurotoxin from bee venom, known to selectively block small conductance of calcium-activated potassium channels (SK), significantly decreased the duration and amplitude of the AHP, an effect that was associated with an increase in spike frequency. In the presence of apamin, bath application of paraoxon reduced the duration of Ca(2+) spike and AHP and increased the firing frequency of nerve cells. In summary, these data suggest that exposure to submicromolar concentration of paraoxon may directly affect membrane excitability. Suppression of Ca(2+) entry during the action potential would down regulate Ca(2+)-activated K(+) channels leading to a reduction of the AHP and an increase in cell firing. PMID:16566905

  9. Single unit action potentials in humans and the effect of seizure activity

    PubMed Central

    Merricks, Edward M.; Smith, Elliot H.; McKhann, Guy M.; Goodman, Robert R.; Bateman, Lisa M.; Emerson, Ronald G.

    2015-01-01

    Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons (‘single units’) from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10–20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of

  10. Stochastic variational learning in recurrent spiking networks

    PubMed Central

    Jimenez Rezende, Danilo; Gerstner, Wulfram

    2014-01-01

    The ability to learn and perform statistical inference with biologically plausible recurrent networks of spiking neurons is an important step toward understanding perception and reasoning. Here we derive and investigate a new learning rule for recurrent spiking networks with hidden neurons, combining principles from variational learning and reinforcement learning. Our network defines a generative model over spike train histories and the derived learning rule has the form of a local Spike Timing Dependent Plasticity rule modulated by global factors (neuromodulators) conveying information about “novelty” on a statistically rigorous ground. Simulations show that our model is able to learn both stationary and non-stationary patterns of spike trains. We also propose one experiment that could potentially be performed with animals in order to test the dynamics of the predicted novelty signal. PMID:24772078

  11. Gifted Potential and Poverty: A Call for Extraordinary Action

    ERIC Educational Resources Information Center

    Kitano, Margie K.

    2003-01-01

    Dr. Robinson's proposed action plan will serve the needs of highly achieving gifted students. However, defining giftedness as high academic performance based on traditional assessment procedures could reverse the field's fledgling success in supporting culturally diverse gifted children and youth. Changing the focus of equity in gifted education…

  12. 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

  13. 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. PMID:27047341

  14. 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

  15. 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

  16. Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials.

    PubMed

    Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

    2014-10-15

    Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl(-) and KATP K(+) ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450-1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above -20 mV. PMID:25128573

  17. Understanding the electrical behavior of the action potential in terms of elementary electrical sources.

    PubMed

    Rodriguez-Falces, Javier

    2015-03-01

    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, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity. PMID:25727465

  18. 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.

  19. 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

  20. Ionic mechanisms involved in the strontium-induced spike and plateau in the smooth muscle of rat portal vein.

    PubMed Central

    Hotta, K; Yamamoto, Y

    1983-01-01

    The action of Sr on the smooth muscle of rat portal vein was studied electrophysiologically using micro-electrodes. By replacing Ca with Sr (2.5 mM), the spontaneous membrane activity was altered and spikes were followed by a long lasting plateau potential. The mechanisms which generated the spike and the plateau in the Sr-induced activity were elucidated. As the concentration of Sr was increased, the peak potential and the maximum rates of rise and fall of the initial spike in each discharge increased. The peak potential varied by 15.2 mV with a 10-fold change in [Sr]o. As there was a decrease in the membrane resistance during the plateau, an increase in the permeability of the membrane for Sr, Cl or Na could be responsible for generation of the plateau. The amplitude of the plateau decreased with increase in the concentration of Sr, remained unchanged in a low-Cl solution, but was diminished in a low-Na solution. Mn (1-2 mM) inhibited not only the spike but also the plateau. TEA (20 mM) shifted the plateau potential in a positive direction and the plateau became permanent. When inward currents were applied in the presence of TEA, spikes with large overshoots and small rates of fall were induced. These results indicate that Sr and K conductances of the membrane generate the spike and that slow-inactivating voltage-dependent Na conductance produces the plateau. PMID:6875907

  1. High-speed recording of neural spikes in awake mice and flies with a fluorescent voltage sensor

    PubMed Central

    Gong, Yiyang; Huang, Cheng; Li, Jin Zhong; Grewe, Benjamin F.; Zhang, Yanping; Eismann, Stephan; Schnitzer, Mark J.

    2016-01-01

    Genetically encoded voltage indicators (GEVIs) are a promising technology for fluorescence readout of millisecond-scale neuronal dynamics. Previous GEVIs had insufficient signaling speed and dynamic range to resolve action potentials in live animals. We coupled fast voltage-sensing domains from a rhodopsin protein to bright fluorophores through resonance energy transfer. The resulting GEVIs are sufficiently bright and fast to report neuronal action potentials and membrane voltage dynamics in awake mice and flies, resolving fast spike trains with 0.2-millisecond timing precision at spike detection error rates orders of magnitude better than previous GEVIs. In vivo imaging revealed sensory-evoked responses, including somatic spiking, dendritic dynamics, and intracellular voltage propagation. These results empower in vivo optical studies of neuronal electrophysiology and coding and motivate further advancements in high-speed microscopy. PMID:26586188

  2. Monitoring Spiking Activity of Many Individual Neurons in Invertebrate Ganglia

    PubMed Central

    Brandon, C.J.; Bruno, A.M.; Humphries, M.D.; Moore-Kochlacs, C.; Sejnowski, T.J.; Wang, J.; Hill, E.S.

    2015-01-01

    Optical recording with fast voltage sensitive dyes makes it possible, in suitable preparations, to simultaneously monitor the action potentials of large numbers of individual neurons. Here we describe methods for doing this, including considerations of different dyes and imaging systems, methods for correlating the optical signals with their source neurons, procedures for getting good signals, and the use of Independent Component Analysis for spike-sorting raw optical data into single neuron traces. These combined tools represent a powerful approach for large-scale recording of neural networks with high temporal and spatial resolution. PMID:26238051

  3. Spiking the Geomagnetic Field

    NASA Astrophysics Data System (ADS)

    Constable, C.; Davies, C. J.

    2015-12-01

    Geomagnetic field intensities corresponding to virtual axial dipole moments of up to 200 ZAm2, more than twice the modern value, have been inferred from archeomagnetic measurements on artifacts dated at or shortly after 1000 BC. Anomalously high values occur in the Levant and Georgia, but not in Bulgaria. The origin of this spike is believed to lie in Earth's core: however, its spatio-temporal characteristics and the geomagnetic processes responsible for such a feature remain a mystery. We show that a localized spike in the radial magnetic field at the core-mantle boundary (CMB) must necessarily contribute to the largest scale changes in Earth's surface field, namely the dipole. Even the limiting spike of a delta function at the CMB produces a minimum surface cap size of 60 degrees for a factor of two increase in paleointensity. Combined evidence from modern satellite and millennial scale field modeling suggests that the Levantine Spike is intimately associated with a strong increase in dipole moment prior to 1000 BC and likely the product of north-westward motion of concentrated near equatorial Asian flux patches like those seen in the modern field. New archeomagnetic studies are needed to confirm this interpretation. Minimum estimates of the power dissipated by the spike are comparable to independent estimates of the dissipation associated with the entire steady state geodynamo. This suggests that geomagnetic spikes are either associated with rapid changes in magnetic energy or strong Lorentz forces.

  4. Metabolic efficiency with fast spiking in the squid axon

    PubMed Central

    Moujahid, Abdelmalik; d'Anjou, Alicia

    2012-01-01

    Fundamentally, action potentials in the squid axon are consequence of the entrance of sodium ions during the depolarization of the rising phase of the spike mediated by the outflow of potassium ions during the hyperpolarization of the falling phase. Perfect metabolic efficiency with a minimum charge needed for the change in voltage during the action potential would confine sodium entry to the rising phase and potassium efflux to the falling phase. However, because sodium channels remain open to a significant extent during the falling phase, a certain overlap of inward and outward currents is observed. In this work we investigate the impact of ion overlap on the number of the adenosine triphosphate (ATP) molecules and energy cost required per action potential as a function of the temperature in a Hodgkin–Huxley model. Based on a recent approach to computing the energy cost of neuronal action potential generation not based on ion counting, we show that increased firing frequencies induced by higher temperatures imply more efficient use of sodium entry, and then a decrease in the metabolic energy cost required to restore the concentration gradients after an action potential. Also, we determine values of sodium conductance at which the hydrolysis efficiency presents a clear minimum. PMID:23162461

  5. Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity

    PubMed Central

    Hall, S.; Hunt, M.; Simon, A.; Cunnington, L.G.; Carracedo, L.M.; Schofield, I.S.; Forsyth, R.; Traub, R.D.

    2015-01-01

    Slow spike and wave discharges (0.5–4 Hz) are a feature of many epilepsies. They are linked to pathology of the thalamocortical axis and a thalamic mechanism has been elegantly described. Here we present evidence for a separate generator in local circuits of associational areas of neocortex manifest from a background, sleep-associated delta rhythm in rat. Loss of tonic neuromodulatory excitation, mediated by nicotinic acetylcholine or serotonin (5HT3A) receptors, of 5HT3-immunopositive interneurons caused an increase in amplitude and slowing of the delta rhythm until each period became the “wave” component of the spike and wave discharge. As with the normal delta rhythm, the wave of a spike and wave discharge originated in cortical layer 5. In contrast, the “spike” component of the spike and wave discharge originated from a relative failure of fast inhibition in layers 2/3—switching pyramidal cell action potential outputs from single, sparse spiking during delta rhythms to brief, intense burst spiking, phase-locked to the field spike. The mechanisms underlying this loss of superficial layer fast inhibition, and a concomitant increase in slow inhibition, appeared to be precipitated by a loss of neuropeptide Y (NPY)-mediated local circuit inhibition and a subsequent increase in vasoactive intestinal peptide (VIP)-mediated disinhibition. Blockade of NPY Y1 receptors was sufficient to generate spike and wave discharges, whereas blockade of VIP receptors almost completely abolished this form of epileptiform activity. These data suggest that aberrant, activity-dependent neuropeptide corelease can have catastrophic effects on neocortical dynamics. PMID:26109655

  6. 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

  7. 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

  8. 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.

  9. Interictal spikes and epileptic seizures: their relationship and underlying rhythmicity.

    PubMed

    Karoly, Philippa J; Freestone, Dean R; Boston, Ray; Grayden, David B; Himes, David; Leyde, Kent; Seneviratne, Udaya; Berkovic, Samuel; O'Brien, Terence; Cook, Mark J

    2016-04-01

    We report on a quantitative analysis of electrocorticography data from a study that acquired continuous ambulatory recordings in humans over extended periods of time. The objectives were to examine patterns of seizures and spontaneous interictal spikes, their relationship to each other, and the nature of periodic variation. The recorded data were originally acquired for the purpose of seizure prediction, and were subsequently analysed in further detail. A detection algorithm identified potential seizure activity and a template matched filter was used to locate spikes. Seizure events were confirmed manually and classified as either clinically correlated, electroencephalographically identical but not clinically correlated, or subclinical. We found that spike rate was significantly altered prior to seizure in 9 out of 15 subjects. Increased pre-ictal spike rate was linked to improved predictability; however, spike rate was also shown to decrease before seizure (in 6 out of the 9 subjects). The probability distribution of spikes and seizures were notably similar, i.e. at times of high seizure likelihood the probability of epileptic spiking also increased. Both spikes and seizures showed clear evidence of circadian regulation and, for some subjects, there were also longer term patterns visible over weeks to months. Patterns of spike and seizure occurrence were highly subject-specific. The pre-ictal decrease in spike rate is not consistent with spikes promoting seizures. However, the fact that spikes and seizures demonstrate similar probability distributions suggests they are not wholly independent processes. It is possible spikes actively inhibit seizures, or that a decreased spike rate is a secondary symptom of the brain approaching seizure. If spike rate is modulated by common regulatory factors as seizures then spikes may be useful biomarkers of cortical excitability.media-1vid110.1093/brain/aww019_video_abstractaww019_video_abstract. PMID:26912639

  10. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    NASA Astrophysics Data System (ADS)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-05-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  11. Complex Dynamic Thresholds and Generation of the Action Potentials in the Neural-Activity Model

    NASA Astrophysics Data System (ADS)

    Kirillov, S. Yu.; Nekorkin, V. I.

    2016-06-01

    This work is devoted to studying the processes of activation of the neurons whose excitation thresholds are not constant and vary in time (the so-called dynamic thresholds). The neuron dynamics is described by the FitzHugh-Nagumo model with nonlinear behavior of the recovery variable. The neuron response to the external pulsed activating action in the presence of a slowly varying synaptic current is studied within the framework of this model. The structure of the dynamic threshold is studied and its properties depending on the external-action parameters are established. It is found that the formation of the "folds" in the separatrix threshold manifold in the model phase space is a typical feature of the complex dynamic threshold. High neuron sensitivity to the action of the comparatively weak slow control signals is established. This explains the capability of the neurons to perform flexible tuning of their selective properties for detecting various external signals in sufficiently short times (of the order of duration of several spikes).

  12. 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.

  13. Noncontact subnanometer measurement of transient surface displacement during action potential propagation

    NASA Astrophysics Data System (ADS)

    Akkin, Taner; Dave, Digant P.; Rylander, H. Grady, III; Milner, Thomas E.

    2005-04-01

    We have demonstrated non-contact, sub-nanometer optical measurement of neural surface displacement associated with action potential propagation without applying exogenous chemicals or reflection coatings. Signals recorded from crayfish leg nerve using a phase-sensitive optical low coherence reflectometer show that transient neural surface displacement due to action potential propagation is approximately 1 nm in amplitude and 1 ms in duration. Measured optical signals are coincident with electrical action potential arrival to the optical measurement site. Recent experiments indicate signals with similar amplitude and duration are observed in response to repetitive fast stimulation (200 stimuli/s).

  14. 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

  15. Stability and Competition in Multi-spike Models of Spike-Timing Dependent Plasticity.

    PubMed

    Babadi, Baktash; Abbott, L F

    2016-03-01

    Spike-timing dependent plasticity (STDP) is a widespread plasticity mechanism in the nervous system. The simplest description of STDP only takes into account pairs of pre- and postsynaptic spikes, with potentiation of the synapse when a presynaptic spike precedes a postsynaptic spike and depression otherwise. In light of experiments that explored a variety of spike patterns, the pair-based STDP model has been augmented to account for multiple pre- and postsynaptic spike interactions. As a result, a number of different "multi-spike" STDP models have been proposed based on different experimental observations. The behavior of these models at the population level is crucial for understanding mechanisms of learning and memory. The challenging balance between the stability of a population of synapses and their competitive modification is well studied for pair-based models, but it has not yet been fully analyzed for multi-spike models. Here, we address this issue through numerical simulations of an integrate-and-fire model neuron with excitatory synapses subject to STDP described by three different proposed multi-spike models. We also analytically calculate average synaptic changes and fluctuations about these averages. Our results indicate that the different multi-spike models behave quite differently at the population level. Although each model can produce synaptic competition in certain parameter regions, none of them induces synaptic competition with its originally fitted parameters. The dichotomy between synaptic stability and Hebbian competition, which is well characterized for pair-based STDP models, persists in multi-spike models. However, anti-Hebbian competition can coexist with synaptic stability in some models. We propose that the collective behavior of synaptic plasticity models at the population level should be used as an additional guideline in applying phenomenological models based on observations of single synapses. PMID:26939080

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

    PubMed

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

    2012-01-01

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

  17. Action potential detection by non-linear microscopy

    NASA Astrophysics Data System (ADS)

    Sacconi, Leonardo; Lotti, Jacopo; O'Connor, Rodney P.; Mapelli, Jonathan; Gandolfi, Daniela; D'Angelo, Egidio; Pavone, Francesco S.

    2009-02-01

    In this work, we combined the advantages of second-harmonic generation (SHG) with a random access (RA) excitation scheme to realize a new microscope (RA-SHG) capable of optically recording fast membrane potential events occurring in a wide-field configuration. The RA-SHG microscope in combination with a bulk staining method with FM4-64 was used to simultaneously record electrical activity from clusters of Purkinje cells (PCs) in acute cerebellar slices. Spontaneous electrical activity was also monitored simultaneously in pairs of neurons, where APs were recorded in a single trial without averaging. These results show the strength of this technique to describe the temporal dynamics of neuronal assemblies.

  18. 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.

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

    PubMed Central

    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.

    2015-01-01

    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. Results We found the highest performance for thresholding when placing a threshold between −3 to −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 was 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. PMID:25504690

  20. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid...

  1. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 13 2012-01-01 2012-01-01 false Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid...

  2. 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

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

    PubMed

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

    2015-02-15

    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

  4. 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

  5. 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. PMID:15182917

  6. 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. PMID:25969124

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

    PubMed

    Kawai, Fusao

    2002-04-01

    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

  8. 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.

  9. Branching Shoots and Spikes from Lateral Meristems in Bread Wheat

    PubMed Central

    Wang, Ying; Miao, Fang; Yan, Liuling

    2016-01-01

    Wheat grain yield consists of three components: spikes per plant, grains per spike (i.e. head or ear), and grain weight; and the grains per spike can be dissected into two subcomponents: spikelets per spike and grains per spikelet. An increase in any of these components will directly contribute to grain yield. Wheat morphology biology tells that a wheat plant has no lateral meristem that forms any branching shoot or spike. In this study, we report two novel shoot and spike traits that were produced from lateral meristems in bread wheat. One is supernumerary shoot that was developed from an axillary bud at the axil of leaves on the elongated internodes of the main stem. The other is supernumerary spike that was generated from a spikelet meristem on a spike. In addition, supernumerary spikelets were generated on the same rachis node of the spike in the plant that had supernumerary shoot and spikes. All of these supernumerary shoots/spikes/spikelets found in the super wheat plants produced normal fertility and seeds, displaying huge yield potential in bread wheat. PMID:26986738

  10. 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.

  11. 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. PMID:25884360

  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. 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.

  14. Neuronal Spike Trains and Stochastic Point Processes

    PubMed Central

    Perkel, Donald H.; Gerstein, George L.; Moore, George P.

    1967-01-01

    In a growing class of neurophysiological experiments, the train of impulses (“spikes”) produced by a nerve cell is subjected to statistical treatment involving the time intervals between spikes. The statistical techniques available for the analysis of single spike trains are described and related to the underlying mathematical theory, that of stochastic point processes, i.e., of stochastic processes whose realizations may be described as series of point events occurring in time, separated by random intervals. For single stationary spike trains, several orders of complexity of statistical treatment are described; the major distinction is that between statistical measures that depend in an essential way on the serial order of interspike intervals and those that are order-independent. The interrelations among the several types of calculations are shown, and an attempt is made to ameliorate the current nomenclatural confusion in this field. Applications, interpretations, and potential difficulties of the statistical techniques are discussed, with special reference to types of spike trains encountered experimentally. Next, the related types of analysis are described for experiments which involve repeated presentations of a brief, isolated stimulus. Finally, the effects of nonstationarity, e.g. long-term changes in firing rate, on the various statistical measures are discussed. Several commonly observed patterns of spike activity are shown to be differentially sensitive to such changes. A companion paper covers the analysis of simultaneously observed spike trains. PMID:4292791

  15. Stability and Competition in Multi-spike Models of Spike-Timing Dependent Plasticity

    PubMed Central

    Babadi, Baktash; Abbott, L. F.

    2016-01-01

    Spike-timing dependent plasticity (STDP) is a widespread plasticity mechanism in the nervous system. The simplest description of STDP only takes into account pairs of pre- and postsynaptic spikes, with potentiation of the synapse when a presynaptic spike precedes a postsynaptic spike and depression otherwise. In light of experiments that explored a variety of spike patterns, the pair-based STDP model has been augmented to account for multiple pre- and postsynaptic spike interactions. As a result, a number of different “multi-spike” STDP models have been proposed based on different experimental observations. The behavior of these models at the population level is crucial for understanding mechanisms of learning and memory. The challenging balance between the stability of a population of synapses and their competitive modification is well studied for pair-based models, but it has not yet been fully analyzed for multi-spike models. Here, we address this issue through numerical simulations of an integrate-and-fire model neuron with excitatory synapses subject to STDP described by three different proposed multi-spike models. We also analytically calculate average synaptic changes and fluctuations about these averages. Our results indicate that the different multi-spike models behave quite differently at the population level. Although each model can produce synaptic competition in certain parameter regions, none of them induces synaptic competition with its originally fitted parameters. The dichotomy between synaptic stability and Hebbian competition, which is well characterized for pair-based STDP models, persists in multi-spike models. However, anti-Hebbian competition can coexist with synaptic stability in some models. We propose that the collective behavior of synaptic plasticity models at the population level should be used as an additional guideline in applying phenomenological models based on observations of single synapses. PMID:26939080

  16. Retractable spiked barrier strip for law enforcement

    SciTech Connect

    Marts, D.J.; Barker, S.G.

    1995-03-01

    The Idaho National Engineering Laboratory has designed an laboratory tested a prototype retractable spiked barrier strip for law enforcement. The proposed system, which is ready for controlled field testing, expands the functionality of existing spiked barrier strips. A retractable barrier strip, one that can place the spikes in either the active (vertical) or passive (horizontal) position, would allow law enforcement personnel to lay the unobtrusive strip across a road far in advance of a fleeing vehicle. No damage occurs to passing vehicles until the spikes are activated, and that can be done from a safe distance and at a strategic location when the offending vehicle is close to the strip. The concept also allows the strips to be place safely across several roadways that are potential paths of a fleeing vehicle. Since they are not activated until needed, they are harmless to nonoffending vehicles. The laboratory tests conducted on the system indicate that it will puncture tires only when the spikes are rotated to the active position and is safe to travel over when the spikes are in the down position. The strip itself will not cause instability to a vehicle driving over it, nor is the strip disturbed or adversely affected by vehicles driving over it. The spikes can be quickly rotated between the active (vertical) and passive (horizontal) position. However, the laboratory tests have only demonstrated that the retractable spiked barrier strip can perform its intended function in a laboratory environment. Field tests are needed to finalize the design and develop the system into a functional law enforcement tool.

  17. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    PubMed

    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 Ca(2+) 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 Ca(2+) 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

  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. Serial correlation in neural spike trains: Experimental evidence, stochastic modeling, and single neuron variability

    NASA Astrophysics Data System (ADS)

    Farkhooi, Farzad; Strube-Bloss, Martin F.; Nawrot, Martin P.

    2009-02-01

    The activity of spiking neurons is frequently described by renewal point process models that assume the statistical independence and identical distribution of the intervals between action potentials. However, the assumption of independent intervals must be questioned for many different types of neurons. We review experimental studies that reported the feature of a negative serial correlation of neighboring intervals, commonly observed in neurons in the sensory periphery as well as in central neurons, notably in the mammalian cortex. In our experiments we observed the same short-lived negative serial dependence of intervals in the spontaneous activity of mushroom body extrinsic neurons in the honeybee. To model serial interval correlations of arbitrary lags, we suggest a family of autoregressive point processes. Its marginal interval distribution is described by the generalized gamma model, which includes as special cases the log-normal and gamma distributions, which have been widely used to characterize regular spiking neurons. In numeric simulations we investigated how serial correlation affects the variance of the neural spike count. We show that the experimentally confirmed negative correlation reduces single-neuron variability, as quantified by the Fano factor, by up to 50%, which favors the transmission of a rate code. We argue that the feature of a negative serial correlation is likely to be common to the class of spike-frequency-adapting neurons and that it might have been largely overlooked in extracellular single-unit recordings due to spike sorting errors.

  20. Serial correlation in neural spike trains: experimental evidence, stochastic modeling, and single neuron variability.

    PubMed

    Farkhooi, Farzad; Strube-Bloss, Martin F; Nawrot, Martin P

    2009-02-01

    The activity of spiking neurons is frequently described by renewal point process models that assume the statistical independence and identical distribution of the intervals between action potentials. However, the assumption of independent intervals must be questioned for many different types of neurons. We review experimental studies that reported the feature of a negative serial correlation of neighboring intervals, commonly observed in neurons in the sensory periphery as well as in central neurons, notably in the mammalian cortex. In our experiments we observed the same short-lived negative serial dependence of intervals in the spontaneous activity of mushroom body extrinsic neurons in the honeybee. To model serial interval correlations of arbitrary lags, we suggest a family of autoregressive point processes. Its marginal interval distribution is described by the generalized gamma model, which includes as special cases the log-normal and gamma distributions, which have been widely used to characterize regular spiking neurons. In numeric simulations we investigated how serial correlation affects the variance of the neural spike count. We show that the experimentally confirmed negative correlation reduces single-neuron variability, as quantified by the Fano factor, by up to 50%, which favors the transmission of a rate code. We argue that the feature of a negative serial correlation is likely to be common to the class of spike-frequency-adapting neurons and that it might have been largely overlooked in extracellular single-unit recordings due to spike sorting errors. PMID:19391776

  1. 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

  2. Increased Event-Related Potentials and Alpha-, Beta-, and Gamma-Activity Associated with Intentional Actions

    PubMed Central

    Karch, Susanne; Loy, Fabian; Krause, Daniela; Schwarz, Sandra; Kiesewetter, Jan; Segmiller, Felix; Chrobok, Agnieszka I.; Keeser, Daniel; Pogarell, Oliver

    2016-01-01

    Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. Methods: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to (1) freely decide whether to press the response button or (2) to decide whether they wanted to press the response button with the right index finger or the left index finger. Results: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go). In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behavior rather than during externally guided responses. Conclusion: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behavior. However, the neural responses were comparatively independent of the kind of decision that was made (1) decision which action to perform; (2) decision whether or not to perform an action). Significance: The study demonstrates the importance of fronto-central alpha-, beta-, and gamma oscillations for voluntary behavior. PMID:26834680

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

    PubMed Central

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

    2012-01-01

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

  4. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-19

    ... Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and... Administration (FAA), Department of Transportation (DOT). ACTION: Notice of availability of a final EA and FONSI/ROD for the evaluation of the potential environmental impacts associated with the proposed Runway...

  5. The cytosolic calcium transient modulates the action potential of rat ventricular myocytes.

    PubMed Central

    duBell, W H; Boyett, M R; Spurgeon, H A; Talo, A; Stern, M D; Lakatta, E G

    1991-01-01

    1. The modulation of the action potential by the cytosolic Ca2+ (Cai2+) transient was studied in single isolated rat ventricular myocytes loaded with the acetoxymethyl ester form of the Ca(2+)-sensitive fluorescent dye Indo-1. Stimulation following rest and exposure to ryanodine were used to change the amount of Ca2+ released from the sarcoplasmic reticulum and thus the size of the Cai2+ transient. The Cai2+ transient was measured as the change, upon stimulation, in the ratio of Indo-1 fluorescence at 410 nm to that at 490 nm (410/490) and action potentials or membrane currents were recorded using patch-type microelectrodes. 2. When stimulation was initiated following rest, the magnitude of the Cai2+ transient decreased in a beat-dependent manner until a steady state was reached. The negative staircase in the Cai2+ transient was accompanied by a similar beat-dependent decrease in the duration of the action potential, manifested primarily as a gradual loss of the action potential plateau (approximately -45 mV). A slow terminal phase of repolarization of a few millivolts in amplitude was found to parallel the terminal decay of the Cai2+ transient. 3. The terminal portion of phase-plane loops of membrane potential (Vm) vs. Indo-1 ratio from all of the beats of a stimulus train followed a common linear trajectory even though the individual beats differed markedly in the duration and amplitude of the action potential and Cai2+ transient. 4. When the stimulation dependence of the Cai2+ transient was titrated away with submaximal exposure to ryanodine, the stimulation-dependent changes in the action potential plateau and terminal phase of repolarization were also eliminated. The same effect was noted in cells which, fortuitously, did not show a staircase in the Cai2+ transient following a period of rest. 5. When action potentials were triggered immediately following spontaneous release of Ca2+ from the sarcoplasmic reticulum, which results in a small depolarization at the

  6. A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

    PubMed

    Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

    2014-09-01

    This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems. PMID:24760928

  7. Prolonged action potential duration in cardiac ablation of PDK1 mice.

    PubMed

    Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

    2015-01-01

    The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis. PMID:26131127

  8. Effect of nanomaterials on the compound action potential of the shore crab, Carcinus maenas.

    PubMed

    Windeatt, Kirsten M; Handy, Richard D

    2013-06-01

    Little is known about the effects of manufactured nanomaterials on the function of nerves. The experiment aimed to test the effects of three different nanomaterials (1 mg l⁻¹ of TiO₂ NPs, Ag NPs or SWCNT) on the compound action potential of the shore crab (Carcinus maenas) compared with an appropriate bulk powder or metal salt control (bulk TiO₂ powder, AgNO₃ and carbon black respectively). In single action potential recordings, there were no effects of any of the nanomaterials on the peak amplitude, duration, rate of rise (depolarisation), or rate of decrease (repolarisation) of the compound action potential in crab saline, despite settling of each nanomaterial directly onto the nerve preparation. The ability of the crab nerve to be stimulated to tetanus was also unaffected by exposure to the nanomaterials compared with the appropriate bulk powder or metal salt control. Solvent controls with sodium dodecyl sulfate (SDS) also had no effect on action potentials. Overall, the study concludes that there were no effects of the materials at the concentrations tested on the compound action potential of the shore crab in physiological saline. PMID:22394242

  9. The role of inward Na(+)-Ca2+ exchange current in the ferret ventricular action potential.

    PubMed Central

    Janvier, N C; Harrison, S M; Boyett, M R

    1997-01-01

    1. Inward Na(+)-Ca2+ exchange current (iNaCa) was either blocked in ferret ventricular cells by replacing extracellular Na+ with Li+ or substantially reduced by the almost complete elimination of the Ca2+ transient by buffering intracellular Ca2+ with the acetoxymethyl ester form of BAPTA (BAPTA AM). 2. During square wave voltage clamp pulses to 0 mV, replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ with BAPTA AM resulted in the loss of a transient inward current. This current was increased by the application of isoprenaline (expected to increase the underlying Ca2+ transient) and displayed the voltage-dependent characteristics of inward iNaCa. 3. Replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ caused a significant shortening of the action potential (at -65 mV, 44 +/- 2% with Li+ and 20 +/- 2% with BAPTA AM). The shortening can be explained by changes in iNaCa. 4. The action potential clamp technique was used to measure the BAPTA-sensitive current (putative iNaCa) and the Ca2+ current (ica; measured using nifedipine) during the action potential. Under control conditions, the inward BAPTA-sensitive current makes approximately the same contribution as iCa during much of the action potential plateau. These results suggest an important role for inward iNaCa in the ferret ventricular action potential. PMID:9051574

  10. 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. PMID:24853946

  11. Spikes in quantum trajectories

    NASA Astrophysics Data System (ADS)

    Tilloy, Antoine; Bauer, Michel; Bernard, Denis

    2015-11-01

    A quantum system subjected to a strong continuous monitoring undergoes quantum jumps. This very-well-known fact hides a neglected subtlety: sharp scale-invariant fluctuations invariably decorate the jump process, even in the limit where the measurement rate is very large. This article is devoted to the quantitative study of these remaining fluctuations, which we call spikes, and to a discussion of their physical status. We start by introducing a classical model where the origin of these fluctuations is more intuitive, and then jump to the quantum realm where their existence is less intuitive. We compute the exact distribution of the spikes for a continuously monitored qubit. We conclude by discussing their physical and operational relevance.

  12. Spike sorting of synchronous spikes from local neuron ensembles.

    PubMed

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

    2015-10-01

    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 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

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

    PubMed Central

    Li, Peijun; Huntsman, Molly M.

    2014-01-01

    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 6 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. PMID:24480365

  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. 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.

  18. 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.

  19. Action potentials induce uniform calcium influx in mammalian myelinated optic nerves.

    PubMed

    Zhang, Chuan-Li; Wilson, J Adam; Williams, Justin; Chiu, Shing Yan

    2006-08-01

    The myelin sheath enables saltatory conduction by demarcating the axon into a narrow nodal region for excitation and an extended, insulated internodal region for efficient spread of passive current. This anatomical demarcation produces a dramatic heterogeneity in ionic fluxes during excitation, a classical example being the restriction of Na influx at the node. Recent studies have revealed that action potentials also induce calcium influx into myelinated axons of mammalian optic nerves. Does calcium influx in myelinated axons show spatial heterogeneity during nerve excitation? To address this, we analyzed spatial profiles of axonal calcium transients during action potentials by selectively staining axons with calcium indicators and subjected the data to theoretical analysis with parameters for axial calcium diffusion empirically determined using photolysis of caged compounds. The results show surprisingly that during action potentials, calcium influx occurs uniformly along an axon of a fully myelinated mouse optic nerve. PMID:16835363

  20. 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 %. PMID:27016364

  1. A Fast Na+/Ca2+-Based Action Potential in a Marine Diatom

    PubMed Central

    Taylor, Alison R.

    2009-01-01

    Background Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. Methodology/Principal Findings The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. Conclusions/Significance This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and successful marine protists

  2. Network Structures Arising from Spike-Timing Dependent Plasticity

    NASA Astrophysics Data System (ADS)

    Babadi, Baktash

    Spike-timing dependent plasticity (STDP), a widespread synaptic modification mechanism, is sensitive to correlations between presynaptic spike trains, and organizes neural circuits in functionally useful ways. In this dissertation, I study the structures arising from STDP in a population of synapses with an emphasis on the interplay between synaptic stability and Hebbian competition, explained in Chapter 1. Starting from the simplest description of STDP which relates synaptic modification to the intervals between pairs of pre- and postsynaptic spikes, I show in Chapter 2 that stability and Hebbian competition are incompatible in this class of "pair-based" STDP models, either when hard bounds or soft bounds are imposed to the synapses. In chapter 3, I propose an alternative biophysically inspired method for imposing bounds to synapses, i.e. introducing a small temporal shift in the STDP window. Shifted STDP overcomes the incompatibility of synaptic stability and competition and can implement both Hebbian and anti-Hebbian forms of competitive plasticity. In light of experiments the explored a variety of spike patterns, STDP models have been augmented to account for interactions between multiple pre- and postsynaptic action potentials. In chapter 4, I study the stability/competition interplay in three different proposed multi-spike models of STDP. I show that the "triplet model" leads to a partially steady-state distribution of synaptic weights and induces Hebbian competition. The "suppression model" develops a stable distribution of weights when the average weight is high and shows predominantly anti-Hebbian competition. The "NMDAR-based" model can lead to either stable or partially stable synaptic weight distribution and exhibits both Hebbian and anti-Hebbian competition, depending on the parameters. I conclude that multi-spike STDP models can produce radically different effects at the population level depending on how they implement multi-spike interactions

  3. 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.

  4. 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

  5. Consensus-Based Sorting of Neuronal Spike Waveforms.

    PubMed

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

    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

  6. 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

  7. 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. PMID:20600047

  8. 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). PMID:16154952

  9. 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. PMID:22710137

  10. 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

  11. Effects of enoxacin and its combination with 4-biphenylacetate, an active metabolite of fenbufen, on population spikes in rat hippocampal slices.

    PubMed

    Ito, T; Miura, Y; Kadokawa, T; Hori, S; Shimada, J; Miyahara, T

    1991-03-01

    The effects of enoxacin, a new quinolone antibacterial agent, and its combination with 4-biphenylacetate (BPA), an active metabolite of the non-steroidal antiinflammatory agent fenbufen, were examined on population spikes induced by electrical stimulation of the stratum radiatum in the CA1 pyramidal cell layer in rat hippocampal slices. Enoxacin (10(-4) M) and bicuculline (10(-6) M) increased the amplitude of the population spikes and anew elicited the second spikes (latency: 10 msec.), while BPA (10(-5) M) decreased the amplitude of the population spikes. However, the combination of enoxacin (10(-6), 10(-5) M) with BPA (10(-5) M) elicited the second spikes or epileptiform bursts with an increase of the population spike amplitude. The dose-response relationships showed that the effect of enoxacin was 100 times potentiated in the presence of BPA (10(-5) M). The second spikes induced by enoxacin (10(-4) M) were suppressed by muscimol (10(-6) M) and baclofen (10(-6) M), but not by clorazepate (5 x 10(-5) M) and pentobarbital (5 x 10(-5) M). The second spikes induced by bicuculline (10(-6) M) were suppressed by these four drugs. The second spikes by the combination of enoxacin (10(-6) M) with BPA (10(-5) M) were suppressed by muscimol (5 x 10(-6) M), but not by clorazepate (5 x 10(-5) M). These results suggest that the combination of enoxacin with BPA exerts a drug interaction to elicit the second spikes or epileptiform bursts with its mode of action different from that of bicuculline. PMID:2057453

  12. Spiking optical patterns and synchronization

    NASA Astrophysics Data System (ADS)

    Rosenbluh, Michael; Aviad, Yaara; Cohen, Elad; Khaykovich, Lev; Kinzel, Wolfgang; Kopelowitz, Evi; Yoskovits, Pinhas; Kanter, Ido

    2007-10-01

    We analyze the time resolved spike statistics of a solitary and two mutually interacting chaotic semiconductor lasers whose chaos is characterized by apparently random, short intensity spikes. Repulsion between two successive spikes is observed, resulting in a refractory period, which is largest at laser threshold. For time intervals between spikes greater than the refractory period, the distribution of the intervals follows a Poisson distribution. The spiking pattern is highly periodic over time windows corresponding to the optical length of the external cavity, with a slow change of the spiking pattern as time increases. When zero-lag synchronization between two lasers is established, the statistics of the nearly perfectly matched spikes are not altered. The similarity of these features to those found in complex interacting neural networks, suggests the use of laser systems as simpler physical models for neural networks.

  13. 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

  14. Spike-timing-dependent plasticity in spiking neuron networks for robot navigation control

    NASA Astrophysics Data System (ADS)

    Arena, Paolo; Danieli, Fabio; Fortuna, Luigi; Frasca, Mattia; Patane, Luca

    2005-06-01

    In this paper a biologically-inspired network of spiking neurons is used for robot navigation control. The implemented scheme is able to process information coming from the robot contact sensors in order to avoid obstacles and on the basis of these actions to learn how to respond to stimuli coming from range finder sensors. The implemented network is therefore able of reinforcement learning through a mechanism based on operant conditioning. This learning takes place according to a plasticity law in the synapses, based on spike timing. Simulation results discussed in the paper show the suitability of the approach and interesting adaptive properties of the network.

  15. CCA-1, EGL-19 and EXP-2 currents shape action potentials in the Caenorhabditis elegans pharynx

    PubMed Central

    Shtonda, Boris; Avery, Leon

    2005-01-01

    The pharynx of Caenorhabditis elegans is a tubular muscle controlled by its own set of neurons. We developed a technique to voltage clamp the pharyngeal muscle and demonstrate by analyzing mutants that the pharyngeal action potential is regulated by three major voltage-gated currents, conducted by a T-type calcium channel CCA-1, an L-type calcium channel EGL-19 and a potassium channel EXP-2. We show that CCA-1 exhibits T-type calcium channel properties: activation at −40 mV and rapid inactivation. Our results suggest that CCA-1’s role is to accelerate the action potential upstroke in the pharyngeal muscle in response to excitatory inputs. Similarly to other L-type channels, EGL-19 activates at high voltages and inactivates slowly; thus it may maintain the plateau phase of the action potential. EXP-2 is a potassium channel of the kV family that shows inward rectifier properties when expressed in Xenopus laevis oocytes. We show that endogenous EXP-2 is not a true inward rectifier – it conducts large outward currents at potentials up to +20 mV and is therefore well suited to trigger rapid repolarization at the end of the action potential plateau phase. Our results suggest that EXP-2 is a potassium channel with unusual properties that uses a hyperpolarization threshold to activate a regenerative hyperpolarizing current. PMID:15914661

  16. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.

    PubMed

    Enomoto, Riyo; Koshiba, Chika; Suzuki, Chie; Lee, Eibai

    2011-05-01

    Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types. Wogonin had no effect on apoptosis induced by other anticancer agents in the tumor cells. Thus, the potentiation effect of wogonin was observed only in etoposide-induced apoptosis in tumor cells. In a functional assay for P-glycoprotein (P-gp), wogonin suppressed excretion of calcein, a substrate for P-gp, in these tumor cells. Moreover, wogonin decreased the excretion of radiolabeled etoposide and accordingly increased intracellular content of this agent in the cells. P-gp inhibitors showed a similar potentiation effect on etoposide-induced apoptosis in these tumor cells. Thus, wogonin is likely to potentiate the anticancer action of etoposide due to P-gp inhibition and accumulation of this agent. These findings suggest that wogonin may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects. PMID:20658136

  17. 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

  18. Spike rate of multi-unit muscle sympathetic nerve fibers after catheter-based renal nerve ablation.

    PubMed

    Tank, Jens; Heusser, Karsten; Brinkmann, Julia; Schmidt, Bernhard M; Menne, Jan; Bauersachs, Johann; Haller, Hermann; Diedrich, André; Jordan, Jens

    2015-10-01

    Patients with treatment-resistant arterial hypertension exhibited profound reductions in single sympathetic vasoconstrictor fiber firing rates after renal nerve ablation. In contrast, integrated multi-unit muscle sympathetic nerve activity (MSNA) changed little or not at all. We hypothesized that conventional MSNA analysis may have missed single fiber discharges, thus, obscuring sympathetic inhibition after renal denervation. We studied patients with difficult-to-control arterial hypertension (age 45-74 years) before, 6 (n = 11), and 12 months (n = 8) after renal nerve ablation. Electrocardiogram, respiration, brachial, and finger arterial blood pressure (BP), as well as the MSNA and raw MSNA signals were analyzed. We detected MSNA action-potential spikes using 2 stage kurtosis wavelet denoising techniques to assess mean, median, and maximum spike rates for each beat-to-beat interval. Supine heart rate and systolic BP did not change at 6 (ΔHR: -2 ± 3 bpm; ΔSBP: 2 ± 9 mm Hg) or at 12 months (ΔHR: -1 ± 3 mm Hg, ΔSBP: -1 ± 9 mm Hg) after renal nerve ablation. Mean burst frequency and mean spike frequency at baseline were 34 ± 3 bursts per minute and 8 ± 1 spikes per second. Both measurements did not change at 6 months (-1.4 ± 3.6 bursts/minute; -0.6 ± 1.4 spikes/second) or at 12 months (-2.5 ± 4.0 bursts/minute; -2.0 ± 1.6 spikes/second) after renal nerve ablation. After renal nerve ablation, BP decreased in 3 of 11 patients. BP and MSNA spike frequency changes were not correlated (slope = -0.06; P = .369). Spike rate analysis of multi-unit MSNA neurograms further suggests that profound sympathetic inhibition is not a consistent finding after renal nerve ablation. PMID:26324745

  19. 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. PMID:26686984

  20. 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.

  1. Spiking models for level-invariant encoding.

    PubMed

    Brette, Romain

    2011-01-01

    Levels of ecological sounds vary over several orders of magnitude, but the firing rate and membrane potential of a neuron are much more limited in range. In binaural neurons of the barn owl, tuning to interaural delays is independent of level differences. Yet a monaural neuron with a fixed threshold should fire earlier in response to louder sounds, which would disrupt the tuning of these neurons. How could spike timing be independent of input level? Here I derive theoretical conditions for a spiking model to be insensitive to input level. The key property is a dynamic change in spike threshold. I then show how level invariance can be physiologically implemented, with specific ionic channel properties. It appears that these ingredients are indeed present in monaural neurons of the sound localization pathway of birds and mammals. PMID:22291634

  2. Activity-dependent control of neuronal output by local and global dendritic spike attenuation.

    PubMed

    Remy, Stefan; Csicsvari, Jozsef; Beck, Heinz

    2009-03-26

    Neurons possess elaborate dendritic arbors which receive and integrate excitatory synaptic signals. Individual dendritic subbranches exhibit local membrane potential supralinearities, termed dendritic spikes, which control transfer of local synaptic input to the soma. Here, we show that dendritic spikes in CA1 pyramidal cells are strongly regulated by specific types of prior input. While input in the linear range is without effect, supralinear input inhibits subsequent spikes, causing them to attenuate and ultimately fail due to dendritic Na(+) channel inactivation. This mechanism acts locally within the boundaries of the input branch. If an input is sufficiently strong to trigger axonal action potentials, their back-propagation into the dendritic tree causes a widespread global reduction in dendritic excitability which is prominent after firing patterns occurring in vivo. Together, these mechanisms control the capability of individual dendritic branches to trigger somatic action potential output. They are invoked at frequencies encountered during learning, and impose limits on the storage and retrieval rates of information encoded as branch excitability. PMID:19323999

  3. Spike timing-dependent serotonergic neuromodulation of synaptic strength intrinsic to a central pattern generator circuit.

    PubMed

    Sakurai, Akira; Katz, Paul S

    2003-11-26

    Neuromodulation is often thought to have a static, gain-setting function in neural circuits. Here we report a counter example: the neuromodulatory effect of a serotonergic neuron is dependent on the interval between its spikes and those of the neuron being modulated. The serotonergic dorsal swim interneurons (DSIs) are members of the escape swim central pattern generator (CPG) in the mollusk Tritonia diomedea. DSI spike trains heterosynaptically enhanced synaptic potentials evoked by another CPG neuron, ventral swim interneuron B (VSI-B), when VSI-B action potentials occurred within 10 sec of a DSI spike train; however, if VSI-B was stimulated 20-120 sec after DSI, then the amplitude of VSI-B synaptic potentials decreased. Consistent with this, VSI-B-evoked synaptic currents exhibited a temporally biphasic and bidirectional change in amplitude after DSI stimulation. Both the DSI-evoked enhancement and decrement were occluded by serotonin and blocked by the serotonin receptor antagonist methysergide, suggesting that both phases are mediated by serotonin. In most preparations, however, bath-applied serotonin caused only a sustained enhancement of VSI-B synaptic strength. The heterosynaptic modulation interacted with short-term homosynaptic plasticity: DSI-evoked depression was offset by VSI-B homosynaptic facilitation. This caused a complicated temporal pattern of neuromodulation when DSI and VSI-B were stimulated to fire in alternating bursts to mimic the natural motor pattern: DSI strongly enhanced summated VSI-B synaptic potentials and suppressed single synaptic potentials after the cessation of the artificial motor pattern. Thus, spike timing-dependent serotonergic neuromodulatory actions can impart temporal information that may be relevant to the operation of the CPG. PMID:14645466

  4. 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

  5. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial actions. 1945.19 Section 1945.19 Agriculture Regulations of the Department of Agriculture (Continued... AGENCY, DEPARTMENT OF AGRICULTURE (CONTINUED) PROGRAM REGULATIONS (CONTINUED) EMERGENCY...

  6. 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…

  7. 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…

  8. Optical recording of action potentials with second-harmonic generation microscopy.

    PubMed

    Dombeck, Daniel A; Blanchard-Desce, Mireille; Webb, Watt W

    2004-01-28

    Nonlinear microscopy has proven to be essential for neuroscience investigations of thick tissue preparations. However, the optical recording of fast (approximately 1 msec) cellular electrical activity has never until now been successfully combined with this imaging modality. Through the use of second-harmonic generation microscopy of primary Aplysia neurons in culture labeled with 4-[4-(dihexylamino)phenyl][ethynyl]-1-(4-sulfobutyl)pyridinium (inner salt), we optically recorded action potentials with 0.833 msec temporal and 0.6 microm spatial resolution on soma and neurite membranes. Second-harmonic generation response as a function of change in membrane potential was found to be linear with a signal change of approximately 6%/100 mV. The signal-to-noise ratio was approximately 1 for single-trace action potential recordings but was readily increased to approximately 6-7 with temporal averaging of approximately 50 scans. Photodamage was determined to be negligible by observing action potential characteristics, cellular resting potential, and gross cellular morphology during and after laser illumination. High-resolution (micrometer scale) optical recording of membrane potential activity by previous techniques has been limited to imaging depths an order of magnitude less than nonlinear methods. Because second-harmonic generation is capable of imaging up to approximately 400 microm deep into intact tissue with submicron resolution and little out-of-focus photodamage or bleaching, its ability to record fast electrical activity should prove valuable to future electrophysiology studies. PMID:14749445

  9. Suppression of spikes during posttetanic hyperpolarization in auditory neurons: the role of temperature, I(h) currents, and the Na(+)-K(+)-ATPase pump.

    PubMed

    Kim, Jun Hee; von Gersdorff, Henrique

    2012-10-01

    In vivo recordings from postsynaptic neurons in the medial nucleus of the trapezoid body (MNTB), an auditory brain stem nucleus, show that acoustic stimulation produces a burst of spikes followed by a period of hyperpolarization and suppressed spiking activity. The underlying mechanism for this hyperpolarization and reduced spiking is unknown. Furthermore, the mechanisms that control excitability and resting membrane potential are not fully determined for these MNTB neurons. In this study we investigated the excitability of principal neurons from the MNTB after high-frequency afferent fiber stimulation, using whole cell recordings from postnatal day 15-17 rat brain stem slices. We found that Na(+)-K(+)-ATPase activity mediates a progressive hyperpolarization during a prolonged tetanic train and a posttetanic hyperpolarization (PTH) at the end of the train, when postsynaptic action potentials failed to fire. Raising the temperature to more physiological levels (from 22 to 35°C) depolarized the resting membrane potential of both presynaptic and postsynaptic cells and decreased the latency of action potential firing during PTH. Higher temperatures also reduced the presynaptic calyx action potential failure rates by 50% during presynaptic PTH, thus increasing the safety-factor for presynaptic spiking. The effect of temperature on hyperpolarization-activated cation current (I(h)) is reflected in the resting potential at both pre- and postsynaptic neurons. We thus propose that temperature-sensitive Na(+)-K(+)-ATPase activity and I(h) contribute to set the resting membrane potential and produce a brief period of suppressed spiking (or action potential failures) after a prolonged high-frequency afferent tetanus. PMID:22786951

  10. 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.

  11. Radioxenon spiked air.

    PubMed

    Watrous, Matthew G; Delmore, James E; Hague, Robert K; Houghton, Tracy P; Jenson, Douglas D; Mann, Nick R

    2015-12-01

    Four of the radioactive xenon isotopes ((131m)Xe, (133m)Xe, (133)Xe and (135)Xe) 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 paper 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. PMID:26318775

  12. Radioxenon spiked air

    DOE PAGESBeta

    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 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

  13. Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties

    PubMed Central

    Ehrlich, Joachim R; Cha, Tae-Joon; Zhang, Liming; Chartier, Denis; Melnyk, Peter; Hohnloser, Stefan H; Nattel, Stanley

    2003-01-01

    Pulmonary vein (PV) cardiomyocytes play an important role in atrial fibrillation; however, little is known about their specific cellular electrophysiological properties. We applied standard microelectrode recording and whole-cell patch-clamp to evaluate action potentials and ionic currents in canine PVs and left atrium (LA) free wall. Resting membrane potential (RMP) averaged −66 ± 1 mV in PVs and −74 ± 1 mV in LA (P < 0.0001) and action potential amplitude averaged 76 ± 2 mV in PVs vs. 95 ± 2 mV in LA (P < 0.0001). PVs had smaller maximum phase 0 upstroke velocity (Vmax: 98 ± 9 vs. 259 ± 16 V s−1, P < 0.0001) and action potential duration (APD): e.g. at 2 Hz, APD to 90 % repolarization in PVs was 84 % of LA (P < 0.05). Na+ current density under voltage-clamp conditions was similar in PV and LA, suggesting that smaller Vmax in PVs was due to reduced RMP. Inward rectifier current density in the PV cardiomyocytes was ˜58 % that in the LA, potentially accounting for the less negative RMP in PVs. Slow and rapid delayed rectifier currents were greater in the PV (by ˜60 and ˜50 %, respectively), whereas transient outward K+ current and L-type Ca2+ current were significantly smaller (by ˜25 and ˜30 %, respectively). Na+-Ca2+-exchange (NCX) current and T-type Ca2+ current were not significantly different. In conclusion, PV cardiomyocytes have a discrete distribution of transmembrane ion currents associated with specific action potential properties, with potential implications for understanding PV electrical activity in cardiac arrhythmias. PMID:12847206

  14. 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

  15. Spike-timing-dependent BDNF secretion and synaptic plasticity.

    PubMed

    Lu, Hui; Park, Hyungju; Poo, Mu-Ming

    2014-01-01

    In acute hippocampal slices, we found that the presence of extracellular brain-derived neurotrophic factor (BDNF) is essential for the induction of spike-timing-dependent long-term potentiation (tLTP). To determine whether BDNF could be secreted from postsynaptic dendrites in a spike-timing-dependent manner, we used a reduced system of dissociated hippocampal neurons in culture. Repetitive pairing of iontophoretically applied glutamate pulses at the dendrite with neuronal spikes could induce persistent alterations of glutamate-induced responses at the same dendritic site in a manner that mimics spike-timing-dependent plasticity (STDP)-the glutamate-induced responses were potentiated and depressed when the glutamate pulses were applied 20 ms before and after neuronal spiking, respectively. By monitoring changes in the green fluorescent protein (GFP) fluorescence at the dendrite of hippocampal neurons expressing GFP-tagged BDNF, we found that pairing of iontophoretic glutamate pulses with neuronal spiking resulted in BDNF secretion from the dendrite at the iontophoretic site only when the glutamate pulses were applied within a time window of approximately 40 ms prior to neuronal spiking, consistent with the timing requirement of synaptic potentiation via STDP. Thus, BDNF is required for tLTP and BDNF secretion could be triggered in a spike-timing-dependent manner from the postsynaptic dendrite. PMID:24298135

  16. The DBI action, higher-derivative supergravity, and flattening inflaton potentials

    NASA Astrophysics Data System (ADS)

    Bielleman, Sjoerd; Ibáñez, Luis E.; Pedro, Francisco G.; Valenzuela, Irene; Wieck, Clemens

    2016-05-01

    In string theory compactifications it is common to find an effective Lagrangian for the scalar fields with a non-canonical kinetic term. We study the effective action of the scalar position moduli of Type II D p-branes. In many instances the kinetic terms are in fact modified by a term proportional to the scalar potential itself. This can be linked to the appearance of higher-dimensional supersymmetric operators correcting the Kähler potential. We identify the supersymmetric dimension-eight operators describing the α' corrections captured by the D-brane Dirac-Born-Infeld action. Our analysis then allows an embedding of the D-brane moduli effective action into an {N}=1 supergravity formulation. The effects of the potential-dependent kinetic terms may be very important if one of the scalars is the inflaton, since they lead to a flattening of the scalar potential. We analyze this flattening effect in detail and compute its impact on the CMB observables for single-field inflation with monomial potentials.

  17. 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.

  18. 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.

  19. 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

  20. Understanding the cardiovascular actions of soy isoflavones: potential novel targets for antihypertensive drug development.

    PubMed

    Martin, Doug; Song, Jin; Mark, Connie; Eyster, Kathleen

    2008-12-01

    Interest in and use of "natural" remedies has grown exponentially in recent years. Compounds that have attracted considerable attention are the isoflavones, particular those found in soy. This review will provide a critical evaluation of our current understanding of the effects, mechanisms of action, and potential clinical applications of soy isoflavones in hypertension. Current data indicate that soy isoflavones, such as genistein and daidzein and equol, relax vascular smooth muscle both in vitro and in vivo via a combination of mechanisms including potentiation of endothelial-dependent and endothelial-independent vasodilator systems and inhibition of constrictor mechanisms. These effects involve both classical genomic as well non genomic actions. Isoflavone actions are mediated in part via interactions with estrogen receptors where soy isoflavones induce unique receptor conformations and exert tissue dependent effects similar to the selective estrogen receptor modulators. Signaling pathways such as ERK1/2, PI3-Kinase/Akt and cAMP contribute to isoflavone isoflavone activation of eNOS in the vasculature as well. Isoflavones also target the kidney to increase renal blood flow and sodium excretion. Finally, soy isoflavones interact with humoral systems such as the renin angiotensin. Data from animal studies show consistently that the aggregate effect of these actions is attenuation of hypertension. In contrast, studies in humans remain controversial. Recent data also suggest that analogues of isoflavones may possess unique vascular actions. Thus significant opportunity remains for study of the effects and mechanisms of action of soy isoflavones on hypertension in both animals and humans. PMID:19202595

  1. Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors

    PubMed Central

    Takahashi, Masazumi; Kubo, Tai; Mizoguchi, Akira; Carlson, C. George; Endo, Katsuaki; Ohnishi, Katsunori

    2002-01-01

    In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: α2βγδ (γ-AChR) or α2βɛδ (ɛ-AChR). After birth, γ-AChRs are replaced by ɛ-AChRs (γ/ɛ-switch). The two receptors have different conductances and open times. During perinatal period, the long open time γ-AChRs generate random myofiber action potentials from uniquantal miniature end-plate potentials (mEPPs). ɛ-AChRs are suitable for strong adult muscle activities. Since the effect of the γ/ɛ-switch on neuromuscular development was unclear, despite the many differences in channel characteristics, we carried out this study to generate γ-subunit-deficient mice. Homozygotes born alive survived for 2 days in a stable condition, and were able to move their forelimbs. Endplate AChRs included ɛ-subunits, and muscle fibers had multiple neuromuscular junctions. Both pre- and postsynapses were abnormal and spontaneous action potentials generated from mEPPs were totally absent. Results suggest a requirement for γ-AChRs in mediating synaptically-induced action potential activity critical for neuromuscular development. PMID:12101101

  2. Spike-timing dependent plasticity in the striatum.

    PubMed

    Fino, Elodie; Venance, Laurent

    2010-01-01

    The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia output nuclei through which it operates a selected activation of behavioral effectors. The striatal output neurons, the GABAergic medium-sized spiny neurons (MSNs), are in charge of the detection and integration of behaviorally relevant information. This property confers to the striatum the ability to extract relevant information from the background noise and select cognitive-motor sequences adapted to environmental stimuli. As long-term synaptic efficacy changes are believed to underlie learning and memory, the corticostriatal long-term plasticity provides a fundamental mechanism for the function of the basal ganglia in procedural learning. Here, we reviewed the different forms of spike-timing dependent plasticity (STDP) occurring at corticostriatal synapses. Most of the studies have focused on MSNs and their ability to develop long-term plasticity. Nevertheless, the striatal interneurons (the fast-spiking GABAergic, NO-synthase and cholinergic interneurons) also receive monosynaptic afferents from the cortex and tightly regulated corticostriatal information processing. Therefore, it is important to take into account the variety of striatal neurons to fully understand the ability of striatum to develop long-term plasticity. Corticostriatal STDP with various spike-timing dependence have been observed depending on the neuronal sub-populations and experimental conditions. This complexity highlights the extraordinary potentiality in term of plasticity of the corticostriatal pathway. PMID:21423492

  3. 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.

  4. Event-related potentials reveal early activation of body part representations in action concept comprehension.

    PubMed

    Lu, Aitao; Liu, Jing; Zhang, John X

    2012-03-01

    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. PMID:22306088

  5. Potentiators of Defective ΔF508-CFTR Gating that Do Not Interfere with Corrector Action.

    PubMed

    Phuan, Puay-Wah; Veit, Guido; Tan, Joseph A; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, A S

    2015-10-01

    Combination drug therapies under development for cystic fibrosis caused by the ∆F508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) include a "corrector" to improve its cellular processing and a "potentiator" to improve its chloride channel function. Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Ivacaftor) reduces ∆F508-CFTR cellular stability and the efficacy of investigational correctors, including 3-(6-[([1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl) amino]-3-methyl-2-pyridinyl)-benzoic acid and 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(2-hydroxy-1,1-dimethylethyl)-1H-indol-5-yl), which might contribute to the modest reported efficacy of combination therapy in clinical trials. Here, we report the identification and characterization of potentiators that do not interfere with ∆F508-CFTR stability or corrector action. High-throughput screening and structure-activity analysis identified several classes of potentiators that do not impair corrector action, including tetrahydrobenzothiophenes, thiooxoaminothiazoles, and pyrazole-pyrrole-isoxazoles. The most potent compounds have an EC(50) for ∆F508-CFTR potentiation down to 18 nM and do not reduce corrector efficacy in heterologous ∆F508-CFTR-expressing cells or primary cultures of ∆F508/∆F508 human bronchial epithelia. The ΔF508-CFTR potentiators also activated wild-type and G551D CFTR, albeit weakly. The efficacy of combination therapy for cystic fibrosis caused by the ∆F508 mutation may be improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector action. PMID:26245207

  6. 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.

  7. Equation-free analysis of spike-timing-dependent plasticity.

    PubMed

    Laing, Carlo R; Kevrekidis, Ioannis G

    2015-12-01

    Spike-timing-dependent plasticity is the process by which the strengths of connections between neurons are modified as a result of the precise timing of the action potentials fired by the neurons. We consider a model consisting of one integrate-and-fire neuron receiving excitatory inputs from a large number-here, 1000-of Poisson neurons whose synapses are plastic. When correlations are introduced between the firing times of these input neurons, the distribution of synaptic strengths shows interesting, and apparently low-dimensional, dynamical behaviour. This behaviour is analysed in two different parameter regimes using equation-free techniques, which bypass the explicit derivation of the relevant low-dimensional dynamical system. We demonstrate both coarse projective integration (which speeds up the time integration of a dynamical system) and the use of recently developed data mining techniques to identify the appropriate low-dimensional description of the complex dynamical systems in our model. PMID:26577337

  8. Screening Fluorescent Voltage Indicators with Spontaneously Spiking HEK Cells

    PubMed Central

    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. PMID:24391999

  9. 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. PMID:24391999

  10. Spontaneous Electrical Activity and Spikes in the Tail of Marine Cercariae

    PubMed Central

    Tolstenkov, O. O.; Zhukovskaya, M. I.; Prokofiev, V. V.; Gustafsson, M. K. S.

    2013-01-01

    Spontaneous electrical activity is recorded in two species of marine cercariae, Cryptocotyle lingua and Himasthla elongata, with different types of swimming—by glass microelectrode recordings. Slow local field potentials (sLFPs) of low amplitude and fast high amplitude action potentials (APs) are found. The shape of the sLFPs is different in the species and correlates with the type of swimming. Fast high amplitude APs are recorded for the first time in cercariae. The limited number of APs included in the swimming pattern of larva suggests a key role for the spiking neurons in initiating the motility pattern in the cercaria and needs further research. PMID:27335850

  11. Performance evaluation of PCA-based spike sorting algorithms.

    PubMed

    Adamos, Dimitrios A; Kosmidis, Efstratios K; Theophilidis, George

    2008-09-01

    Deciphering the electrical activity of individual neurons from multi-unit noisy recordings is critical for understanding complex neural systems. A widely used spike sorting algorithm is being evaluated for single-electrode nerve trunk recordings. The algorithm is based on principal component analysis (PCA) for spike feature extraction. In the neuroscience literature it is generally assumed that the use of the first two or most commonly three principal components is sufficient. We estimate the optimum PCA-based feature space by evaluating the algorithm's performance on simulated series of action potentials. A number of modifications are made to the open source nev2lkit software to enable systematic investigation of the parameter space. We introduce a new metric to define clustering error considering over-clustering more favorable than under-clustering as proposed by experimentalists for our data. Both the program patch and the metric are available online. Correlated and white Gaussian noise processes are superimposed to account for biological and artificial jitter in the recordings. We report that the employment of more than three principal components is in general beneficial for all noise cases considered. Finally, we apply our results to experimental data and verify that the sorting process with four principal components is in agreement with a panel of electrophysiology experts. PMID:18565614

  12. Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing

    PubMed Central

    Ford, Marc C.; Alexandrova, Olga; Cossell, Lee; Stange-Marten, Annette; Sinclair, James; Kopp-Scheinpflug, Conny; Pecka, Michael; Attwell, David; Grothe, Benedikt

    2015-01-01

    Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing. PMID:26305015

  13. A reconstruction of charge movement during the action potential in frog skeletal muscle.

    PubMed Central

    Huang, C. L.; Peachey, L. D.

    1992-01-01

    The transfer of intramembrane charge during an action potential at 4 degrees C was reconstructed for a model representing the electrical properties of frog skeletal muscle by a cylindrical surface membrane and 16 concentric annuli ("shells") of transverse tubular membrane of equal radial thickness. The lumina of the transverse tubules were separated from extracellular fluid by a fixed series resistance. The quantity, geometrical distribution and steady-state and kinetic properties of charge movement components were described by equations incorporating earlier experimental results. Introducing such nonlinear charge into the distributed model for muscle membrane diminished the maximum amplitude of the action potential within the transverse tubules by 2 mV but increased the maximum size of the after-depolarization by 3-5 mV and also its duration. However, these changes were small in comparison to the 135-mV deflection represented by the action potential. They therefore did not justify altering the values of the electrical parameters adopted by Adrian R.H., and L.D. Peachey (1973. J. Physiol. [Lond.]. 235:103-131.) and used in the present calculations. Cable properties significantly affected the time course and extent of charge movement in each shell during action potential propagation into the tubular system. Q beta charge moved relatively rapidly in all annuli, and did so without significant latency (approximately 0.3 ms) after the surface action potential upstroke. Its peak displacement varied between 53 and 58% (the range representing the difference fiber edge/fiber axis) of the total Q beta charge. This was attained at 5.4-7.3 ms after the stimulus, depending on depth within the tubules. In contrast, q gamma moved after a 1.7-2.9 ms latency and achieved a peak displacement of up to 22-34% of available charge. Both charge movement species could be driven by repetitive (47.7 Hz) action potentials without buildup of charge transfer. Such stimulus frequencies would

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

    PubMed Central

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

    2014-01-01

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

  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. Real-time imaging of action potentials in nerves using changes in birefringence.

    PubMed

    Badreddine, Ali H; Jordan, Tomas; Bigio, Irving J

    2016-05-01

    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

  17. Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing.

    PubMed

    Ford, Marc C; Alexandrova, Olga; Cossell, Lee; Stange-Marten, Annette; Sinclair, James; Kopp-Scheinpflug, Conny; Pecka, Michael; Attwell, David; Grothe, Benedikt

    2015-01-01

    Action potential timing is fundamental to information processing; however, its determinants are not fully understood. Here we report unexpected structural specializations in the Ranvier nodes and internodes of auditory brainstem axons involved in sound localization. Myelination properties deviated significantly from the traditionally assumed structure. Axons responding best to low-frequency sounds had a larger diameter than high-frequency axons but, surprisingly, shorter internodes. Simulations predicted that this geometry helps to adjust the conduction velocity and timing of action potentials within the circuit. Electrophysiological recordings in vitro and in vivo confirmed higher conduction velocities in low-frequency axons. Moreover, internode length decreased and Ranvier node diameter increased progressively along the distal axon segments, which simulations show was essential to ensure precisely timed depolarization of the giant calyx of Held presynaptic terminal. Thus, individual anatomical parameters of myelinated axons can be tuned to optimize pathways involved in temporal processing. PMID:26305015

  18. Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs.

    PubMed

    Rieger, R; Taylor, J; Comi, E; Donaldson, N; Russold, M; Mahony, C M O; McLaughlin, J A; McAdams, E; Demosthenous, A; Jarvis, J C

    2004-07-01

    Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented. PMID:15234689

  19. An indirect component in the evoked compound action potential of the vagal nerve.

    PubMed

    Ordelman, Simone C M A; Kornet, Lilian; Cornelussen, Richard; Buschman, Hendrik P J; Veltink, Peter H

    2010-12-01

    The vagal nerve plays a vital role in the regulation of the cardiovascular system. It not only regulates the heart but also sends sensory information from the heart back to the brain. We hypothesize that the evoked vagal nerve compound action potential contains components that are indirect via the brain stem or coming via the neural network on the heart. In an experimental study of 15 pigs, we identified four components in the evoked compound action potentials. The fourth component was found to be an indirect component, which came from the periphery. The latency of the indirect component increased when heart rate and contractility were decreased by burst stimulation (P = 0.01; n = 7). When heart rate and contractility were increased by dobutamine administration, the latency of the indirect component decreased (P = 0.01; n = 9). This showed that the latency of the indirect component of the evoked compound action potentials may relate to the state of the cardiovascular system. PMID:20966537

  20. 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. PMID:26492070

  1. Mechanisms of action potential propagation failure at sites of axon branching in the crayfish.

    PubMed Central

    Smith, D O

    1980-01-01

    1. The phenomena leading to action potential conduction block during repetitive stimulation of the excitor axon of the opener muscle in the crayfish walking leg were studied. 2. Action potentials, recorded extracellularly with micro-electrodes, failed to propagate past sites of axonal bifurcation following at least 3000 impulses; reduction of the rate or brief cessation of stimulation resulted in restored conduction. 3. Failure occurred initially at branch points located most peripherally and then more centrally as stimulation continued; this centripetal progression of the site of block resulted in a stepwise reduction of the number of synaptic terminals from which transmitter was released. 4. Prior to conduction failure, the conduction velocity and the sodium inward current of the action potentials decreased. 5. Local application of hyperpolarizing current or of physiological saline with low [K+] in the vicinity of a block can restore propagation; thus depolarization of the membrane most probably causes failure. 6. Soaking the preparation for as long as 2 hr in the metabolic inhibitor 2,4-dinitrophenol had no effect on the number of stimulus impulses before initial conduction block; however, the time required for recovery from the failure was prolonged. 7. The number of impulses prior to block was related directly to the temperature of the preparation; this had a Q10 calculated to be about 1 . 3. 8. It is suggested that during repetitive activity, the K+ gradient across the membrane is reduced, resulting in depolarization and eventually in conduction failure. PMID:7411430

  2. Shensong Yangxin capsules prevent ischemic arrhythmias by prolonging action potentials and alleviating Ca2+ overload.

    PubMed

    Zhao, Yixiu; Gao, Feng; Zhang, Yong; Wang, Hongtao; Zhu, Jiuxin; Chang, Liping; Du, Zhimin; Zhang, Yan

    2016-06-01

    Shensong Yangxin capsules (SSYX) are an effective traditional Chinese medicine that has been used to treat coronary heart disease clinically. The present study aimed to establish whether SSYX prevent ischemic arrhythmias in rats, and to explore the underlying mechanisms. Male rats were pretreated with distilled water, SSYX and amiodarone for one week. Acute myocardial ischemia (AMI) was performed to induce ischemic arrhythmias. The incidence and severity of ischemic arrhythmias were evaluated. The action potential, transient outward K+ current (Ito) and inward rectifier K+ current (IK1) of rat cardiomyocytes were measured using the patch‑clamp technique. The intracellular Ca2+ concentration of the cardiomyocytes was measured using a laser scanning confocal microscope. The results revealed that SSYX lowered the incidence of arrhythmia markedly during AMI. Furthermore, SSYX delayed the appearance, and reduced the severity, of ischemic arrhythmias compared with the control. In addition, SSYX markedly decreased the ratio of the myocardial infarction region to the whole heart. In an in vitro study, SSYX prolonged the action potential duration of rat cardiomyocytes, and inhibited Ito and IK1 markedly. Additionally, SSYX inhibited Ca2+ elevation induced by KCl in cardiomyocytes. These results suggested that SSYX prevents ischemic arrhythmia, and the underlying mechanism responsible for this process may include prolonging the action potential and alleviating Ca2+ overload. PMID:27122298

  3. Heart rate variability effect on the myocyte action potential duration restitution: insights from switched systems theory.

    PubMed

    Dvir, Hila; Zlochiver, Sharon

    2011-01-01

    The physiological heart rate presents a stochastic behavior known as heart rate variability (HRV). In this framework the influence of HRV on the action potential duration (APD) of the atrial myocyte is analyzed in a computer model. We have found that introducing HRV into the myocyte action potential model decreases the APD of the extra beat S2 in an S1-S2 protocol compared to constant heart rate. A possible theoretical explanation for this is also presented and is derived from switched systems theory. It is suggested to consider the myocyte action potential phase 4 and phase 2 as two operation modes of a switching system and analyze the stability of switching between them. Since random switching is known to have a stabilization effect on a switching system, this might explain why HRV has a stabilization effect on the myocyte APD restitution. Implications of this finding include reduced system stability for conditions with low HRV. A possible application for this phenomenon regards artificial pacemakers, where a preset added HRV is predicted to reduce susceptibility to arrhythmias. PMID:22254402

  4. Optical recording of action potentials in mammalian neurons using a microbial rhodopsin

    PubMed Central

    Kralj, Joel M.; Douglass, Adam D.; Hochbaum, Daniel R.; Maclaurin, Dougal; Cohen, Adam E.

    2011-01-01

    Reliable optical detection of single action potentials in mammalian neurons has been one of the longest-standing challenges in neuroscience. Here we achieve this goal by using the endogenous fluorescence of a microbial rhodopsin protein, Archaerhodopsin 3 (Arch) from Halorubrum sodomense, expressed in cultured rat hippocampal neurons. This genetically encoded voltage indicator exhibited an approximately 10-fold improvement in sensitivity and speed over existing protein-based voltage indicators, with a roughly linear two-fold increase in brightness between −150 mV and +150 mV and a sub-millisecond response time. Arch detected single electrically triggered action potentials with an optical signal-to-noise ratio > 10. The mutant Arch(D95N) lacked endogenous proton pumping and showed 50% greater sensitivity than wild-type, but had a slower response (41 ms). Nonetheless, Arch(D95N) also resolved individual action potentials. Microbial rhodopsin-based voltage indicators promise to enable optical interrogation of complex neural circuits, and electrophysiology in systems for which electrode-based techniques are challenging. PMID:22120467

  5. A 0.7 V, 40 nW Compact, Current-Mode Neural Spike Detector in 65 nm CMOS.

    PubMed

    Yao, Enyi; Chen, Yi; Basu, Arindam

    2016-04-01

    In this paper, we describe a novel low power, compact, current-mode spike detector circuit for real-time neural recording systems where neural spikes or action potentials (AP) are of interest. Such a circuit can enable massive compression of data facilitating wireless transmission. This design can generate a high signal-to-noise ratio (SNR) output by approximating the popularly used nonlinear energy operator (NEO) through standard analog blocks. We show that a low pass filter after the NEO can be used for two functions-(i) estimate and cancel low frequency interference and (ii) estimate threshold for spike detection. The circuit is implemented in a 65 nm CMOS process and occupies 200 μm × 150 μ m of chip area. Operating from a 0.7 V power supply, it consumes about 30 nW of static power and 7 nW of dynamic power for 100 Hz input spike rate making it the lowest power consuming spike detector reported so far. PMID:26168445

  6. 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

  7. 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. PMID:23774164

  8. Spike processing with a graphene excitable laser.

    PubMed

    Shastri, Bhavin J; Nahmias, Mitchell A; Tait, Alexander N; Rodriguez, Alejandro W; Wu, Ben; Prucnal, Paul R

    2016-01-01

    Novel materials and devices in photonics have the potential to revolutionize optical information processing, beyond conventional binary-logic approaches. Laser systems offer a rich repertoire of useful dynamical behaviors, including the excitable dynamics also found in the time-resolved "spiking" of neurons. Spiking reconciles the expressiveness and efficiency of analog processing with the robustness and scalability of digital processing. We demonstrate a unified platform for spike processing with a graphene-coupled laser system. We show that this platform can simultaneously exhibit logic-level restoration, cascadability and input-output isolation--fundamental challenges in optical information processing. We also implement low-level spike-processing tasks that are critical for higher level processing: temporal pattern detection and stable recurrent memory. We study these properties in the context of a fiber laser system and also propose and simulate an analogous integrated device. The addition of graphene leads to a number of advantages which stem from its unique properties, including high absorption and fast carrier relaxation. These could lead to significant speed and efficiency improvements in unconventional laser processing devices, and ongoing research on graphene microfabrication promises compatibility with integrated laser platforms. PMID:26753897

  9. Spike-Timing Theory of Working Memory

    PubMed Central

    Szatmáry, Botond; Izhikevich, Eugene M.

    2010-01-01

    Working memory (WM) is the part of the brain's memory system that provides temporary storage and manipulation of information necessary for cognition. Although WM has limited capacity at any given time, it has vast memory content in the sense that it acts on the brain's nearly infinite repertoire of lifetime long-term memories. Using simulations, we show that large memory content and WM functionality emerge spontaneously if we take the spike-timing nature of neuronal processing into account. Here, memories are represented by extensively overlapping groups of neurons that exhibit stereotypical time-locked spatiotemporal spike-timing patterns, called polychronous patterns; and synapses forming such polychronous neuronal groups (PNGs) are subject to associative synaptic plasticity in the form of both long-term and short-term spike-timing dependent plasticity. While long-term potentiation is essential in PNG formation, we show how short-term plasticity can temporarily strengthen the synapses of selected PNGs and lead to an increase in the spontaneous reactivation rate of these PNGs. This increased reactivation rate, consistent with in vivo recordings during WM tasks, results in high interspike interval variability and irregular, yet systematically changing, elevated firing rate profiles within the neurons of the selected PNGs. Additionally, our theory explains the relationship between such slowly changing firing rates and precisely timed spikes, and it reveals a novel relationship between WM and the perception of time on the order of seconds. PMID:20808877

  10. Stochastically Gating Ion Channels Enable Patterned Spike Firing through Activity-Dependent Modulation of Spike Probability

    PubMed Central

    Dudman, Joshua T.; Nolan, Matthew F.

    2009-01-01

    The transformation of synaptic input into patterns of spike output is a fundamental operation that is determined by the particular complement of ion channels that a neuron expresses. Although it is well established that individual ion channel proteins make stochastic transitions between conducting and non-conducting states, most models of synaptic integration are deterministic, and relatively little is known about the functional consequences of interactions between stochastically gating ion channels. Here, we show that a model of stellate neurons from layer II of the medial entorhinal cortex implemented with either stochastic or deterministically gating ion channels can reproduce the resting membrane properties of stellate neurons, but only the stochastic version of the model can fully account for perithreshold membrane potential fluctuations and clustered patterns of spike output that are recorded from stellate neurons during depolarized states. We demonstrate that the stochastic model implements an example of a general mechanism for patterning of neuronal output through activity-dependent changes in the probability of spike firing. Unlike deterministic mechanisms that generate spike patterns through slow changes in the state of model parameters, this general stochastic mechanism does not require retention of information beyond the duration of a single spike and its associated afterhyperpolarization. Instead, clustered patterns of spikes emerge in the stochastic model of stellate neurons as a result of a transient increase in firing probability driven by activation of HCN channels during recovery from the spike afterhyperpolarization. Using this model, we infer conditions in which stochastic ion channel gating may influence firing patterns in vivo and predict consequences of modifications of HCN channel function for in vivo firing patterns. PMID:19214199

  11. 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

  12. Continuous functions determined by spike trains of a neuron subject to stimulation.

    PubMed

    Awiszus, F

    1988-01-01

    Several ways of estimating a continuous function from the spike train output of a neuron subjected to repeated stimuli are compared: (i) the probability of firing function estimated by a PST-histogram (ii) the rate of discharge function estimated by a "frequencygram" (Bessou et al. 1968) and (iii) the interspike-interval function which is introduced in this paper. For a special class of neuronal responses, called deterministic, these functions may be expressed in terms of each other. It is shown that the current clamped Hodgkin-Huxley model of an action potential encoding membrane (Hodgkin and Huxley 1952) is able to generate such deterministic responses. As an experimental example, a deterministic response of a primary muscle spindle afferent is used to demonstrate the estimation of the functions. Interpretability and numerical estimatability of these spike train describing functions are discussed for deterministic neuronal responses. PMID:3382703

  13. 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. PMID:26344775

  14. Action-space Clustering of Tidal Streams to Infer the Galactic Potential

    NASA Astrophysics Data System (ADS)

    Sanderson, Robyn E.; Helmi, Amina; Hogg, David W.

    2015-03-01

    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.

  15. 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

  16. Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

    PubMed Central

    Taggart, P; Sutton, P; John, R; Lab, M; Swanton, H

    1992-01-01

    OBJECTIVE--The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS--Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS--23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING--Tertiary referral centre for cardiology. RESULTS--In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal

  17. An online spike detection and spike classification algorithm capable of instantaneous resolution of overlapping spikes

    PubMed Central

    Natora, Michal; Boucsein, Clemens; Munk, Matthias H. J.; Obermayer, Klaus

    2009-01-01

    For the analysis of neuronal cooperativity, simultaneously recorded extracellular signals from neighboring neurons need to be sorted reliably by a spike sorting method. Many algorithms have been developed to this end, however, to date, none of them manages to fulfill a set of demanding requirements. In particular, it is desirable to have an algorithm that operates online, detects and classifies overlapping spikes in real time, and that adapts to non-stationary data. Here, we present a combined spike detection and classification algorithm, which explicitly addresses these issues. Our approach makes use of linear filters to find a new representation of the data and to optimally enhance the signal-to-noise ratio. We introduce a method called “Deconfusion” which de-correlates the filter outputs and provides source separation. Finally, a set of well-defined thresholds is applied and leads to simultaneous spike detection and spike classification. By incorporating a direct feedback, the algorithm adapts to non-stationary data and is, therefore, well suited for acute recordings. We evaluate our method on simulated and experimental data, including simultaneous intra/extra-cellular recordings made in slices of a rat cortex and recordings from the prefrontal cortex of awake behaving macaques. We compare the results to existing spike detection as well as spike sorting methods. We conclude that our algorithm meets all of the mentioned requirements and outperforms other methods under realistic signal-to-noise ratios and in the presence of overlapping spikes. PMID:19499318

  18. Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study.

    PubMed

    Sundt, Danielle; Gamper, Nikita; Jaffe, David B

    2015-12-01

    Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na(+) channels. A model containing only fast voltage-gated Na(+) and delayed-rectifier K(+) channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca(2+)-dependent K(+) current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na(+)-K(+) pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca(2+)-dependent K(+) current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain. PMID:26334005

  19. Spike propagation through the dorsal root ganglia in an unmyelinated sensory neuron: a modeling study

    PubMed Central

    Sundt, Danielle; Gamper, Nikita

    2015-01-01

    Unmyelinated C-fibers are a major type of sensory neurons conveying pain information. Action potential conduction is regulated by the bifurcation (T-junction) of sensory neuron axons within the dorsal root ganglia (DRG). Understanding how C-fiber signaling is influenced by the morphology of the T-junction and the local expression of ion channels is important for understanding pain signaling. In this study we used biophysical computer modeling to investigate the influence of axon morphology within the DRG and various membrane conductances on the reliability of spike propagation. As expected, calculated input impedance and the amplitude of propagating action potentials were both lowest at the T-junction. Propagation reliability for single spikes was highly sensitive to the diameter of the stem axon and the density of voltage-gated Na+ channels. A model containing only fast voltage-gated Na+ and delayed-rectifier K+ channels conducted trains of spikes up to frequencies of 110 Hz. The addition of slowly activating KCNQ channels (i.e., KV7 or M-channels) to the model reduced the following frequency to 30 Hz. Hyperpolarization produced by addition of a much slower conductance, such as a Ca2+-dependent K+ current, was needed to reduce the following frequency to 6 Hz. Attenuation of driving force due to ion accumulation or hyperpolarization produced by a Na+-K+ pump had no effect on following frequency but could influence the reliability of spike propagation mutually with the voltage shift generated by a Ca2+-dependent K+ current. These simulations suggest how specific ion channels within the DRG may contribute toward therapeutic treatments for chronic pain. PMID:26334005

  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 Central

    Pearman, Charles M.

    2014-01-01

    Abstract 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. PMID:25501439

  2. Phase Relationship between Alternans of Early and Late Phases of Ventricular Action Potentials

    PubMed Central

    Jing, Linyuan; Agarwal, Anuj; Chourasia, Sonam; Patwardhan, Abhijit

    2012-01-01

    Background: Alternans of early phase and of duration of action potential (AP) critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of eight swine and three canines during paced activation intervals of ≤300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max) and of action potential duration (APD). Incidence of APD alternans was 62 and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26% were out of phase in swine and canines, i.e., low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusion: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord. PMID:22701104

  3. 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

  4. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays

    NASA Astrophysics Data System (ADS)

    Fujishiro, Akifumi; Kaneko, Hidekazu; Kawashima, Takahiro; Ishida, Makoto; Kawano, Takeshi

    2014-05-01

    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.

  5. In vivo neuronal action potential recordings via three-dimensional microscale needle-electrode arrays.

    PubMed

    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

  6. 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

  7. Monophasic action potentials and Ca2+ transients in ischaemically preconditioned rabbit ventricular muscle

    PubMed Central

    Dekker, L.R.C.; van Bavel, E.; Opthof, T.; Coronel, R.; Janse, M.J.

    2003-01-01

    Background ATP-sensitive K+ (KATP) channels play an important role in the protective mechanism underlying ischaemic preconditioning. Ample evidence indicates, however, that action potential shortening is not a prerequisite for the cardioprotective effect of preconditioning. Methods Monophasic action potential duration (MAPD), tissue resistance, intracellular Ca2+ (Indo-1) and mechanical activity were simultaneously assessed in arterially perfused rabbit papillary muscles. We studied four experimental protocols preceding sustained ischaemia: 1. control perfusion (n=6), 2. ischaemic preconditioning (PC; n=4), 3. pretreatment with a KATP channel blocker, glibenclamide (15 μmol/1), prior to ischaemic preconditioning (PC+glib; n=3), 4. glibenclamide pretreatment only (Glib; n=2). Results In the PC group an increase in the diastolic Ca2+ level and a prolongation of the Ca2+ transient just prior to the induction of sustained ischaemia correlate to the postponement of the onset of irreversible ischaemic damage, as established by a rise in [Ca2+]i, electrical uncoupling and contracture. Glibenclamide antagonised these changes in the Ca2+ transient and the cardioprotection induced by preconditioning. MAPD was equal in all experimental groups. Conclusions Prolongation of the Ca2+ transient and increase of diastolic [Ca2+]i just prior to the induction of sustained ischaemia and not action potential shortening are involved in the cardioprotective effect of ischaemic preconditioning. Therefore, a glibenclamide-sensitive mechanism, other than the sarcolemmal KATP channels, is involved in the protective effect of ischaemic preconditioning. Changes in Ca2+ metabolism may play a crucial role in ischaemic preconditioning. ImagesFigure 1 PMID:25696182

  8. Electrophysiological properties of rat spinal dorsal horn neurones in vitro: calcium-dependent action potentials.

    PubMed Central

    Murase, K; Randić, M

    1983-01-01

    1. The electrophysiological properties of dorsal horn neurones have been investigated in the immature rat in vitro spinal cord slice preparation. 2. Intracellular recordings from dorsal horn neurones show that direct or orthodromic stimulation generates action potentials followed by a brief after-hyperpolarization. Synaptic potentials were elicited by the activation of primary afferent fibres in the dorsal root. 3. Input resistance for dorsal horn neurones ranged from 48 to 267 M omega, and the membrane time constant was in the range of 4-19 ms. 4. In response to strong depolarizing currents dorsal horn neurones perfused with TTX and TEA frequently exhibit a slow regenerative depolarizing potential followed by a slow after-hyperpolarization. The depolarizing potential probably results from an influx of Ca. It is blocked by low concentration Ca, Co or Mn, and enhanced by high levels of extracellular Ca. 5. There is, in addition, a low-threshold Ca-dependent response which is activated at membrane potentials more negative than -65 mV and has a maximum rate of rise at the polarization level of about -80 mV. 6. The addition of Ba or TEA to the perfusing medium provided support for the Ca-dependence of the low- and high-threshold responses, and the lack of fast inactivation of the high-threshold Ca potential. Images Plate 1 PMID:6306228

  9. THE SOLAR DECIMETRIC SPIKE BURST OF 2006 DECEMBER 6: POSSIBLE EVIDENCE FOR FIELD-ALIGNED POTENTIAL DROPS IN POST-ERUPTION LOOPS

    SciTech Connect

    Cliver, E. W.; White, S. M.; Balasubramaniam, K. S.

    2011-12-20

    A 1.4 GHz solar radio burst associated with a 3B/X6 eruptive flare on 2006 December 6 had the highest peak flux density ({approx}10{sup 6} sfu) of any event yet recorded at this frequency. The decimetric event characteristics during the brightest emission phase (numerous intense, short-lived, narrow-band bursts that overlapped to form a continuous spectrum) suggest electron cyclotron maser (ECM) emission. The peak 1.4 GHz emission did not occur during the flare impulsive phase but rather {approx}45 minutes later, in association with post-eruption loop activity seen in H{alpha} and by the Hinode EUV Imaging Spectrometer. During the Waves/LASCO era, three other delayed bursts with peak intensities >10{sup 5} sfu in the 1.0-1.6 GHz (L-band) frequency range have been reported that appear to have characteristics similar to the December 6 burst. In each of these three cases, high-frequency type IV bursts were reported in a range from {approx}150 to {approx}1500 MHz. Assuming a common ECM emission mechanism across this frequency range implies a broad span of source heights in the associated post-eruption loop systems. Difficulties with an ECM interpretation for these events include the generation of the lower frequency component of the type IVs and the long-standing problem of escape of the ECM emission from the loops. Magnetic-field-aligned potential drops, analogous to those observed for Earth's auroral kilometric radiation, could plausibly remove both of these objections to ECM emission.

  10. Dynamical speckles patterns of action potential transmission effects in squid giant axon membrane

    NASA Astrophysics Data System (ADS)

    Llovera-González, Juan J.; Moreno-Yeras, Alfredo B.; Muramatsu, Mikiya; Soga, Diogo; Serra-Toledo, Rolando L.; Magalhães, Daniel S. F.

    2013-11-01

    Undoubtedly the most important result of the investigations in physiology and biophysics was the discovery of the electrochemical mechanism of propagation of the action potential in nerves that was made by Hodgkin and Huxley during the first half of the past century. Since some decades ago diverse experiments about the electro optical properties of the axon membrane there was published using the most diverse optical experimental procedures6-10. In this paper some results of a dynamical speckle technique applied for obtaining microscopic images of a section of a squid giant axon membrane during the activation by electrical impulses and his digital process are presented.

  11. Simulation of ECG Repolarization Phase with Improved Model of Cell Action Potentials

    NASA Astrophysics Data System (ADS)

    Trobec, Roman; Depolli, Matjaž; Avbelj, Viktor

    An improved model of action potentials (AP) is proposed to increase the accuracy of simulated electrocardiograms (ECGs). ECG simulator is based on a spatial model of a left ventricle, composed of cubic cells. Three distinct APs, modeled with functions proposed by Wohlfard, have been assigned to the cells, forming epicardial, mid, and endocardial layers. Identification of exact parameter values for AP models has been done through optimization of the simulated ECGs. Results have shown that only through an introduction of a minor extension to the AP model, simulator is able to produce more realistic ECGs. The same extension also proves essential for achieving a better fit between the measured and modeled APs.

  12. A Quantitative Description of the Relationship between the Area of Rabbit Ventricular Action Potentials and the Pattern of Stimulation

    PubMed Central

    Gibbs, C. L.; Johnson, E. A.; Tille, J.

    1963-01-01

    Intracellular microelectrodes were used to record action potentials from fibres of the isolated rabbit right ventricle and the areas of the action potentials were measured. The action potential area was found to depend in a reproducible way on the preceding pattern of stimulation. A mathematical model reproducing all the observed changes in the action potential area was developed. In the model the action potential area is taken as a linear function of the product of two time and stimulation dependent variables, M and N. The behaviour of each variable between action potentials is described by the solution of a second order differential equation. During each action potential the variables are assumed to change discontinuously, the magnitudes of the discontinuous changes being given by a set of subsidiary equations. It was found that the behaviour of all the fibres tested was described by the same set of equations, each single fibre being characterized by a set of ten independent constants. ImagesFigure 5 PMID:14070359

  13. Geophone with depth sensitive spikes

    SciTech Connect

    Rice, J.A.; Houston, L.M.; Arevalo, R.

    1992-06-23

    This patent describes a geophone. It comprises a seismic sensitive element for sensing elastic motion and converting the motion to an electrical signal, a housing for enclosing the seismic element, and an elongated spike attachable to the housing.

  14. A method to measure the strength of multi-unit bursts of action potentials.

    PubMed

    Mulloney, Brian

    2005-07-15

    Both the numbers of neurons that are active during multi-unit bursts of spikes and the frequencies with which individual neurons fire in these bursts can vary in response to changes in excitation. Here is a digital-filtering method that measures the strength of a burst of spikes by calculating the area of a polygon derived from the squared voltages that record the burst, and dividing this area by the burst's duration. The method was developed in the SigmaPlot environment, and makes use of the Fast-Fourier Transform functions provided in the SigmaPlot transform language. To test the method's performance, I constructed multi-unit bursts of spikes with known structure and calculated the strengths of these known bursts. To demonstrate the method's usefulness, I applied it to a train of 23 bursts of spikes in motor axons recorded during a spontaneous bout of patterned motor output. The measured strengths of these bursts varied 30-fold, and were well-correlated with the differences in the original recording. The results demonstrate that the method effectively measures burst strength independent of burst duration. PMID:15935226

  15. VLSI Implementation of a Bio-inspired Olfactory Spiking Neural Network

    NASA Astrophysics Data System (ADS)

    Hsieh, Hung-Yi; Tang, Kea-Tiong

    2011-11-01

    This paper proposes a VLSI circuit implementing a low power, high-resolution spiking neural network (SNN) with STDP synapses, inspired by mammalian olfactory systems. By representing mitral cell action potential by a step function, the power consumption and the chip area can be reduced. By cooperating sub-threshold oscillation and inhibition, the network outputs can be distinct. This circuit was fabricated using the TSMC 0.18 μm 1P6M CMOS process. Post-layout simulation results are reported.

  16. Spike-count distribution in a neuronal population under weak common stimulation

    NASA Astrophysics Data System (ADS)

    Kruscha, Alexandra; Lindner, Benjamin

    2015-11-01

    We study the probability distribution of the number of synchronous action potentials (spike count) in a model network consisting of a homogeneous neural population that is driven by a common time-dependent stimulus. We derive two analytical approximations for the count statistics, which are based on linear response theory and hold true for weak input correlations. Comparison to numerical simulations of populations of integrate-and-fire neurons in different parameter regimes reveals that our theory correctly predicts how much a weak common stimulus increases the probability of common firing and of common silence in the neural population.

  17. Spikes and ribbon synapses in early vision.

    PubMed

    Baden, Tom; Euler, Thomas; Weckström, Matti; Lagnado, Leon

    2013-08-01

    Image processing begins in the retina, where neurons respond with graded voltage changes that must be converted into spikes. This conversion from 'analog' to 'digital' coding is a fundamental transformation carried out by the visual system, but the mechanisms are still not well understood. Recent work demonstrates that, in vertebrates, graded-to-spiking conversion of the visual signal begins in the axonal system of bipolar cells (BCs), which transmit visual information through ribbon-type synapses specialized for responding to graded voltage signals. Here, we explore the evidence for and against the idea that ribbon synapses also transmit digital information. We then discuss the potential costs and benefits of digitization at different stages of visual pathways in vertebrates and invertebrates. PMID:23706152

  18. Afterhyperpolarization (AHP) regulates the frequency and timing of action potentials in the mitral cells of the olfactory bulb: role of olfactory experience

    PubMed Central

    Duménieu, Maël; Fourcaud-Trocmé, Nicolas; Garcia, Samuel; Kuczewski, Nicola

    2015-01-01

    Afterhyperpolarization (AHP) is a principal feedback mechanism in the control of the frequency and patterning of neuronal firing. In principal projection neurons of the olfactory bulb, the mitral cells (MCs), the AHP is produced by three separate components: classical potassium-mediated hyperpolarization, and the excitatory and inhibitory components, which are generated by the recurrent dendrodendritic synaptic transmission. Precise spike timing is involved in olfactory coding and learning, as well as in the appearance of population oscillatory activity. However, the contribution of the AHP and its components to these processes remains unknown. In this study, we demonstrate that the AHP is developed with the MC firing frequency and is dominated by the potassium component. We also show that recurrent synaptic transmission significantly modifies MC AHP and that the strength of the hyperpolarization produced by the AHP in the few milliseconds preceding the action potential (AP) emission determines MC firing frequency and AP timing. Moreover, we show that the AHP area is larger in younger animals, possibly owing to increased Ca2+ influx during MC firing. Finally, we show that olfactory experience selectively reduces the early component of the MC AHP (under 25 msec), thus producing a modification of the AP timing limited to the higher firing frequency. On the basis of these results, we propose that the AHP, and its susceptibility to be selectively modulated by the recurrent synaptic transmission and olfactory experience, participate in odor coding and learning by modifying the frequency and pattern of MC firing. PMID:26019289

  19. Flavonoids: a review of probable mechanisms of action and potential applications.

    PubMed

    Nijveldt, R J; van Nood, E; van Hoorn, D E; Boelens, P G; van Norren, K; van Leeuwen, P A

    2001-10-01

    The aim of this review, a summary of the putative biological actions of flavonoids, was to obtain a further understanding of the reported beneficial health effects of these substances. Flavonoids occur naturally in fruit, vegetables, and beverages such as tea and wine. Research in the field of flavonoids has increased since the discovery of the French paradox,ie, the low cardiovascular mortality rate observed in Mediterranean populations in association with red wine consumption and a high saturated fat intake. Several other potential beneficial properties of flavonoids have since been ascertained. We review the different groups of known flavonoids, the probable mechanisms by which they act, and the potential clinical applications of these fascinating natural substances. PMID:11566638

  20. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates.

    PubMed

    Schlaepfer, Charles H; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell's motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium's large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students' laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around -30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20-30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature's conclusion in a V-Gated Ca(++) influx and depolarization resulting in feedback from intracellular Ca(++) that inactivates V-Gated Ca(++) channels and activates Ca-Dependent K(+) channels through a secondary messenger cascade that results in the K(+) efflux and repolarization. PMID:26557800

  1. Action of hallucinogens on raphe-evoked dorsal root potentials (DRPs) in the cat.

    PubMed

    Larson, A A; Anderson, E G

    1986-02-01

    The dorsal root potential (DRP) evoked by stimulation of the inferior central nucleus (ICN) of the cat is affected by administration of a variety of hallucinogenic agents. It has been previously shown that a single low dose of LSD is unique in that it potentiates this DRP, while injections of 5-methoxy-N,N- dimethyltryptamine (5-MeODMT), ketamine or phencyclidine (PCP) inhibit its production. Tolerance develops to the facilitatory effect of low doses of LSD on the DRP, but not to the inhibitory action of 5-MeODMT. Repeated injections of ketamine every 30 minutes also fail to produce tachyphylaxis to the inhibitory effect of this dissociative anesthetic. The raphe-evoked DRP is a long latency potential that is inhibited by a wide variety of putative serotonin antagonists and has therefore been traditionally thought to be mediated by serotonin. However, in light of the inability of either tryptophan or fluoxetine to potentiate this DRP, and the resistance of this DRP to blockade by parachlorophenylalanine, reserpine or intrathecally administered 5,7-dihydroxytryptamine, it appears that this potential may in fact be mediated, at least in part, by a non-serotonergic transmitter. PMID:3952125

  2. Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites.

    PubMed

    Acker, Corey D; Antic, Srdjan D

    2009-03-01

    Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree. PMID:19118105

  3. Interactions of ethanol and quinidine on contractility and myocyte action potential in the rat ventricle.

    PubMed

    Guthrie, S K; Wilde, D W; Brown, R A; Savage, A O; Bleske, B

    1995-01-01

    The combined effects of ethanol and quinidine on cardiac electromechanical coupling are unknown, but both drugs affect cardiac conduction and can cause myocardial depression. Isolated left ventricular papillary and ventricular myocytes were used to assess the combined effects of quinidine and ethanol on the electrophysiologic and mechanical properties of rat myocardium. The combination of quinidine (1-300 microM) and ethanol (120-240 mg/dL) depressed active papillary muscle tension within the clinically useful concentration range. In electrophysiologic studies of isolated ventricular myocytes, quinidine prolonged the action potential duration at 50% (APD50) and 90% (APD90) repolarization, the absolute refractory period, and the relative refractory period, but decreased the maximum rate of change of depolarization in phase 0 (Vmax). When cells were exposed to ethanol (240 mg/dL) and quinidine (1.5 microM) together, a significant decrease in the quinidine-induced prolongation of the absolute refractory and relative refractory periods was seen. Additional changes in action potential parameters from the quinidine values included slight reductions in Vmax and in APD50 and APD90, but these reductions were not consistently displayed, nor were they statistically significant. PMID:7897336

  4. 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

  5. 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

  6. 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

  7. Computational and Electronic Analog Implementation of the Hodgkin-Huxley Model of Action Potentials in Neurons

    NASA Astrophysics Data System (ADS)

    Smith, Peter; Link, Justin

    2012-02-01

    Alan Loyd Hodgkin and Andrew Huxley's mathematical model of action potential initiation and propagation in neurons is one of the greatest hallmarks of biophysics. Two techniques for implementing the Hodgkin-Huxley model were explored: computational and electronic analog. Computational modeling was done using NEURON 7.1. NEURON is a free, robust, and relatively user friendly simulation environment that enables quantitatively accurate computational modeling of neurons and neural networks. An analog electronic circuit was built using field-effect transistors (FETs) to simulate the non-linear, voltage-dependent (sodium and potassium) conductances that are responsible for membrane excitability. While the electronic analog qualitatively reproduces many of the key features of the action potential including overall shape, inactivation period, and propagation, it was difficult to quantitatively reproduce the Hodgkin-Huxley model. In addition, while the relative cost to build circuits equivalent to small membrane patches is minimal (˜50), implementation of larger cells or networks would prove uneconomical. Still, both techniques are viable avenues toward introducing interdisciplinary research into either a computational or electronics lab setting at the undergraduate level.

  8. Peripheral Hot Spots for Local Ca2+ Release after Single Action Potentials in Sympathetic Ganglion Neurons

    PubMed Central

    Cseresnyés, Zoltán; Schneider, Martin F.

    2004-01-01

    Ca2+ release from the endoplasmic reticulum (ER) contributes to Ca2+ transients in frog sympathetic ganglion neurons. Here we use video-rate confocal fluo-4 fluorescence imaging to show that single action potentials reproducibly trigger rapidly rising Ca2+ transients at 1–3 local hot spots within the peripheral ER-rich layer in intact neurons in fresh ganglia and in the majority (74%) of cultured neurons. Hot spots were located near the nucleus or the axon hillock region. Other regions exhibited either slower and smaller signals or no response. Ca2+ signals spread into the cell at constant velocity across the ER in nonnuclear regions, indicating active propagation, but spread with a (time)1/2 dependence within the nucleus, consistent with diffusion. 26% of cultured cells exhibited uniform Ca2+ signals around the periphery, but hot spots were produced by loading the cytosol with EGTA or by bathing such cells in low-Ca2+ Ringer's solution. Peripheral hot spots for Ca2+ release within the perinuclear and axon hillock regions provide a mechanism for preferential initiation of nuclear and axonal Ca2+ signals by single action potentials in sympathetic ganglion neurons. PMID:14695260

  9. 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

  10. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools

    PubMed Central

    Frey, Scott H.; Povinelli, Daniel J.

    2012-01-01

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use. PMID:22106426

  11. Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

    PubMed Central

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T. Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed

  12. Comparison of magnetoencephalographic spikes with and without concurrent electroencephalographic spikes in extratemporal epilepsy.

    PubMed

    Park, Hyeon-Mi; Nakasato, Nobukazu; Iwasaki, Masaki; Shamoto, Hiroshi; Tominaga, Teiji; Yoshimoto, Takashi

    2004-07-01

    Interictal spikes in patients with epilepsy may be detected by either electroencephalography (EEG) (E-spikes) or magnetoencephalography (MEG) (M-spikes), or both MEG and EEG (E/M-spikes). Localization and amplitude were compared between E/M-spikes and M-spikes in 7 adult patients with extratemporal epilepsy to evaluate the clinical significance of MEG spikes. MEG and EEG were simultaneously measured using a helmet-shaped MEG system with planar-type gradiometers and scalp electrodes of the international 10-20 system. Sources of E/M-spikes and M-spikes were estimated by an equivalent current dipole (ECD) model for MEG at peak latency. Each subject showed 9 to 20 (mean 13.4) E/M-spikes and 9 to 31 (mean 16.3) M-spikes. No subjects showed significant differences in the ECD locations between E/M- and M-spikes. ECD moments of the E/M-spikes were significantly larger in 2 patients and not significantly different in the other 5 patients. The similar localizations of E/M-spikes and M-spikes suggest that combination of MEG and EEG is useful to detect more interictal spikes in patients with extratemporal epilepsy. The smaller tendency of ECD amplitude of the M-spikes than E/M-spikes suggests that scalp EEG may overlook small tangential spikes due to background brain noise. Localization value of M-spikes is clinically equivalent to that of E/M-spikes. PMID:15240925

  13. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

    ERIC Educational Resources Information Center

    Adult Learning, 2012

    2012-01-01

    This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

  14. Self-consistent determination of the spike-train power spectrum in a neural network with sparse connectivity

    PubMed Central

    Dummer, Benjamin; Wieland, Stefan; Lindner, Benjamin

    2014-01-01

    A major source of random variability in cortical networks is the quasi-random arrival of presynaptic action potentials from many other cells. In network studies as well as in the study of the response properties of single cells embedded in a network, synaptic background input is often approximated by Poissonian spike trains. However, the output statistics of the cells is in most cases far from being Poisson. This is inconsistent with the assumption of similar spike-train statistics for pre- and postsynaptic cells in a recurrent network. Here we tackle this problem for the popular class of integrate-and-fire neurons and study a self-consistent statistics of input and output spectra of neural spike trains. Instead of actually using a large network, we use an iterative scheme, in which we simulate a single neuron over several generations. In each of these generations, the neuron is stimulated with surrogate stochastic input that has a similar statistics as the output of the previous generation. For the surrogate input, we employ two distinct approximations: (i) a superposition of renewal spike trains with the same interspike interval density as observed in the previous generation and (ii) a Gaussian current with a power spectrum proportional to that observed in the previous generation. For input parameters that correspond to balanced input in the network, both the renewal and the Gaussian iteration procedure converge quickly and yield comparable results for the self-consistent spike-train power spectrum. We compare our results to large-scale simulations of a random sparsely connected network of leaky integrate-and-fire neurons (Brunel, 2000) and show that in the asynchronous regime close to a state of balanced synaptic input from the network, our iterative schemes provide an excellent approximations to the autocorrelation of spike trains in the recurrent network. PMID:25278869

  15. External potassium and action potential propagation in rat fast and slow twitch muscles.

    PubMed

    Kössler, F; Lange, F; Caffier, G; Küchler, G

    1991-10-01

    The role of extracellular K+ concentration in the propagation velocity of action potential was tested in isolated rat skeletal muscles. Different K+ concentrations were produced by KCl additions to extracellular solution. Action potentials were measured extracellularly by means of two annular platinum electrodes. Fibre bundles of m. soleus (SOL), m. extensor digitorum longus (EDL), red (SMR) and white (SMW) part of m. sternomastoideus were maximum stimulated. The conduction velocity (c.v.) was calculated from the distance between the electrodes and the time delay of the potentials measured at 22 degrees C. In Tyrode solution containing 5 mmol/l K+, the c.v. was close to 1 m.s-1. Bundles of the fast muscle type seemed to have a somewhat higher c.v. The differences observed in these studies were not significant. At higher temperatures, the c.v. increased (Q10 of approx. 2) and a dissociation between SMR and SMW muscles appeared. An elevation of K+ concentration to 10 mmol/l induced a drop of the c.v. by approx. 25% and 15% in EDL and SOL muscles, respectively. After return to normal solution, the recovery was not complete within 30 min. In K+ free solution the c.v. of EDL and SM muscles rose by a factor of 1.5, but less in SOL muscles. The weaker response of SOL to K+ modification was related to the higher resistance of this muscle to fatigue. This suggestion was supported by experiments on fatigued fibre bundles. Immediately after a tetanic stimulation producing fatigue, the c.v. of EDL and SOL muscles dropped similarly as in 10 mmol/l K+; again, the drop was less for SOL muscles. Adrenaline (0.5-10.0 mumol/l) enhanced both the c.v. and the twitch amplitude. The results support the suggestion that extracellular K+ accumulation during activity is an essential factor of muscle fatigue. PMID:1816028

  16. Detection and Isolation of Swine Influenza A Virus in Spiked Oral Fluid and Samples from Individually Housed, Experimentally Infected Pigs: Potential Role of Porcine Oral Fluid in Active Influenza A Virus Surveillance in Swine

    PubMed Central

    Decorte, Inge; Steensels, Mieke; Lambrecht, Bénédicte

    2015-01-01

    Background The lack of seasonality of swine influenza A virus (swIAV) in combination with the capacity of swine to harbor a large number of co-circulating IAV lineages, resulting in the risk for the emergence of influenza viruses with pandemic potential, stress the importance of swIAV surveillance. To date, active surveillance of swIAV worldwide is barely done because of the short detection period in nasal swab samples. Therefore, more sensitive diagnostic methods to monitor circulating virus strains are requisite. Methods qRT-PCR and virus isolations were performed on oral fluid and nasal swabs collected from individually housed pigs that were infected sequentially with H1N1 and H3N2 swIAV strains. The same methods were also applied to oral fluid samples spiked with H1N1 to study the influence of conservation time and temperature on swIAV infectivity and detectability in porcine oral fluid. Results All swIAV infected animals were found qRT-PCR positive in both nasal swabs and oral fluid. However, swIAV could be detected for a longer period in oral fluid than in nasal swabs. Despite the high detectability of swIAV in oral fluid, virus isolation from oral fluid collected from infected pigs was rare. These results are supported by laboratory studies showing that the PCR detectability of swIAV remains unaltered during a 24 h incubation period in oral fluid, while swIAV infectivity drops dramatically immediately upon contact with oral fluid (3 log titer reduction) and gets lost after 24 h conservation in oral fluid at ambient temperature. Conclusions Our data indicate that porcine oral fluid has the potential to replace nasal swabs for molecular diagnostic purposes. The difficulty to isolate swIAV from oral fluid could pose a drawback for its use in active surveillance programs. PMID:26431039

  17. Distinct Kv Channel Subtypes Contribute to Differences in Spike Signaling Properties in the Axon Initial Segment and Presynaptic Boutons of Cerebellar Interneurons

    PubMed Central

    Rowan, Matthew J. M.; Tranquil, Elizabeth

    2014-01-01

    The discrete arrangement of voltage-gated K+ (Kv) channels in axons may impart functional advantages in action potential (AP) signaling yet, in compact cell types, the organization of Kv channels is poorly understood. We find that in cerebellar stellate cell interneurons of mice, the composition and influence of Kv channels populating the axon is diverse and depends on location allowing axonal compartments to differentially control APs in a local manner. Kv1 channels determine AP repolarization at the spike initiation site but not at more distal sites, limiting the expression of use-dependent spike broadening to the most proximal axon region, likely a key attribute informing spiking phenotype. Local control of AP repolarization at presynaptic boutons depends on Kv3 channels keeping APs brief, thus limiting Ca2+ influx and synaptic strength. These observations suggest that AP repolarization is tuned by the local influence of distinct Kv channel types, and this organization enhances the functional segregation of axonal compartments. PMID:24806686

  18. Analysis of Neuronal Spike Trains, Deconstructed.

    PubMed

    Aljadeff, Johnatan; Lansdell, Benjamin J; Fairhall, Adrienne L; Kleinfeld, David

    2016-07-20

    As information flows through the brain, neuronal firing progresses from encoding the world as sensed by the animal to driving the motor output of subsequent behavior. One of the more tractable goals of quantitative neuroscience is to develop predictive models that relate the sensory or motor streams with neuronal firing. Here we review and contrast analytical tools used to accomplish this task. We focus on classes of models in which the external variable is compared with one or more feature vectors to extract a low-dimensional representation, the history of spiking and other variables are potentially incorporated, and these factors are nonlinearly transformed to predict the occurrences of spikes. We illustrate these techniques in application to datasets of different degrees of complexity. In particular, we address the fitting of models in the presence of strong correlations in the external variable, as occurs in natural sensory stimuli and in movement. Spectral correlation between predicted and measured spike trains is introduced to contrast the relative success of different methods. PMID:27477016

  19. Spike processing with a graphene excitable laser

    PubMed Central

    Shastri, Bhavin J.; Nahmias, Mitchell A.; Tait, Alexander N.; Rodriguez, Alejandro W.; Wu, Ben; Prucnal, Paul R.

    2016-01-01

    Novel materials and devices in photonics have the potential to revolutionize optical information processing, beyond conventional binary-logic approaches. Laser systems offer a rich repertoire of useful dynamical behaviors, including the excitable dynamics also found in the time-resolved “spiking” of neurons. Spiking reconciles the expressiveness and efficiency of analog processing with the robustness and scalability of digital processing. We demonstrate a unified platform for spike processing with a graphene-coupled laser system. We show that this platform can simultaneously exhibit logic-level restoration, cascadability and input-output isolation—fundamental challenges in optical information processing. We also implement low-level spike-processing tasks that are critical for higher level processing: temporal pattern detection and stable recurrent memory. We study these properties in the context of a fiber laser system and also propose and simulate an analogous integrated device. The addition of graphene leads to a number of advantages which stem from its unique properties, including high absorption and fast carrier relaxation. These could lead to significant speed and efficiency improvements in unconventional laser processing devices, and ongoing research on graphene microfabrication promises compatibility with integrated laser platforms. PMID:26753897

  20. Spike processing with a graphene excitable laser

    NASA Astrophysics Data System (ADS)

    Shastri, Bhavin J.; Nahmias, Mitchell A.; Tait, Alexander N.; Rodriguez, Alejandro W.; Wu, Ben; Prucnal, Paul R.

    2016-01-01

    Novel materials and devices in photonics have the potential to revolutionize optical information processing, beyond conventional binary-logic approaches. Laser systems offer a rich repertoire of useful dynamical behaviors, including the excitable dynamics also found in the time-resolved “spiking” of neurons. Spiking reconciles the expressiveness and efficiency of analog processing with the robustness and scalability of digital processing. We demonstrate a unified platform for spike processing with a graphene-coupled laser system. We show that this platform can simultaneously exhibit logic-level restoration, cascadability and input-output isolation—fundamental challenges in optical information processing. We also implement low-level spike-processing tasks that are critical for higher level processing: temporal pattern detection and stable recurrent memory. We study these properties in the context of a fiber laser system and also propose and simulate an analogous integrated device. The addition of graphene leads to a number of advantages which stem from its unique properties, including high absorption and fast carrier relaxation. These could lead to significant speed and efficiency improvements in unconventional laser processing devices, and ongoing research on graphene microfabrication promises compatibility with integrated laser platforms.

  1. Spike-dip transformation of Setaria viridis.

    PubMed

    Saha, Prasenjit; Blumwald, Eduardo

    2016-04-01

    Traditional method of Agrobacterium-mediated transformation through the generation of tissue culture had limited success for Setaria viridis, an emerging C4 monocot model. Here we present an efficient in planta method for Agrobacterium-mediated genetic transformation of S. viridis using spike dip. Pre-anthesis developing spikes were dipped into a solution of Agrobacterium tumefaciens strain AGL1 harboring the β-glucuronidase (GUS) reporter gene driven by the cauliflower mosaic virus 35S (CaMV35S) promoter to standardize and optimize conditions for transient as well as stable transformations. A transformation efficiency of 0.8 ± 0.1% was obtained after dipping of 5-day-old S3 spikes for 20 min in Agrobacterium cultures containing S. viridis spike-dip medium supplemented with 0.025% Silwet L-77 and 200 μm acetosyringone. Reproducibility of this method was demonstrated by generating stable transgenic lines expressing β-glucuronidase plus (GUSplus), green fluorescent protein (GFP) and Discosoma sp. red fluorescent protein (DsRed) reporter genes driven by either CaMV35S or intron-interrupted maize ubiquitin (Ubi) promoters from three S. viridis genotypes. Expression of these reporter genes in transient assays as well as in T1 stable transformed plants was monitored using histochemical, fluorometric GUS activity and fluorescence microscopy. Molecular analysis of transgenic lines revealed stable integration of transgenes into the genome, and inherited transgenes expressed in the subsequent generations. This approach provides opportunities for the high-throughput transformation and potentially facilitates translational research in a monocot model plant. PMID:26932666

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

    PubMed

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

    2012-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

  4. Potential Mechanisms of Action in the Treatment of Social Impairment and Disorganization in Adolescents with ADHD

    PubMed Central

    Evans, Steven W.; Schultz, Brandon K.; Zoromski, Allison K.

    2014-01-01

    Two important domains that can be impaired in adolescents with ADHD are organization and social functioning; however, the development of interventions to target these areas in adolescents is in the early stages. Currently, small efficacy trials are beginning to be used to conduct preliminary tests on the proposed mechanisms of action for these interventions. These two studies examined the efficacy of organization and social functioning interventions for adolescents with ADHD, as well as the potential mechanisms of action for each intervention. Results from the organization intervention provide support for a significant relationship between performance on the organization checklist and overall GPA; however, there was no meaningful pattern of relationships between achieving mastery of the organization tasks and grades within quarter. Further, results from the social functioning intervention support a moderate relationship between performance on process measures of response to the intervention and outcome measures of social functioning. Results of this study provide implications for modifications to the measures and intervention procedures in future research. PMID:24748901

  5. A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty

    PubMed Central

    Dixon, David; Coates, Jonathon; del Carpio Pons, Alicia; Horabin, Joanna; Walker, Andrew; Abdul, Nicole; Kalson, Nicholas S.; Brewster, Nigel T.; Weir, David J.; Deehan, David J.; Mann, Derek A.; Borthwick, Lee A.

    2015-01-01

    Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/β will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/β induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/β treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/β availability and not their ability to respond to it. PMID:26553966

  6. Cancer Driver Log (CanDL): Catalog of Potentially Actionable Cancer Mutations.

    PubMed

    Damodaran, Senthilkumar; Miya, Jharna; Kautto, Esko; Zhu, Eliot; Samorodnitsky, Eric; Datta, Jharna; Reeser, Julie W; Roychowdhury, Sameek

    2015-09-01

    Massively parallel sequencing technologies have enabled characterization of genomic alterations across multiple tumor types. Efforts have focused on identifying driver mutations because they represent potential targets for therapy. However, because of the presence of driver and passenger mutations, it is often challenging to assign the clinical relevance of specific mutations observed in patients. Currently, there are multiple databases and tools that provide in silico assessment for potential drivers; however, there is no comprehensive resource for mutations with functional characterization. Therefore, we created an expert-curated database of potentially actionable driver mutations for molecular pathologists to facilitate annotation of cancer genomic testing. We reviewed scientific literature to identify variants that have been functionally characterized in vitro or in vivo as driver mutations. We obtained the chromosome location and all possible nucleotide positions for each amino acid change and uploaded them to the Cancer Driver Log (CanDL) database with associated literature reference indicating functional driver evidence. In addition to a simple interface, the database allows users to download all or selected genes as a comma-separated values file for incorporation into their own analysis pipeline. Furthermore, the database includes a mechanism for third-party contributions to support updates for novel driver mutations. Overall, this freely available database will facilitate rapid annotation of cancer genomic testing in molecular pathology laboratories for mutations. PMID:26320871

  7. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

    PubMed

    Arnold, W David; Sheth, Kajri A; Wier, Christopher G; Kissel, John T; Burghes, Arthur H; Kolb, Stephen J

    2015-01-01

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons. PMID:26436455

  8. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    PubMed Central

    Li, Wentao; Xu, Haoliang; Testai, Fernando D.

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood–brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke. PMID:27617002

  9. Effects of lead acetate on guinea pig - cochear microphonics, action potential, and motor nerve conduction velocity

    SciTech Connect

    Yamamura, K.; Maehara, N.; Terayama, K.; Ueno, N.; Kohyama, A.; Sawada, Y.; Kishi, R.

    1987-04-01

    Segmental demyelination and axonal degeneration of motor nerves induced by lead exposure is well known in man, and animals. The effect of lead acetate exposure to man may involve the cranial nerves, since vertigo and sensory neuronal deafness have been reported among lead workers. However, there are few reports concerning the dose-effects of lead acetate both to the peripheral nerve and the cranial VII nerve with measurement of blood lead concentration. The authors investigated the effects of lead acetate to the cochlea and the VIII nerve using CM (cochlear microphonics) and AP (action potential) of the guinea pigs. The effects of lead acetate to the sciatic nerve were measured by MCV of the sciatic nerve with measurement of blood lead concentration.

  10. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke.

    PubMed

    Li, Wentao; Xu, Haoliang; Testai, Fernando D

    2016-01-01

    Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood-brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720's mechanisms of action in stroke. PMID:27617002

  11. Anthropomorphizing the Mouse Cardiac Action Potential via a Novel Dynamic Clamp Method

    PubMed Central

    Ahrens-Nicklas, Rebecca C.; Christini, David J.

    2009-01-01

    Abstract Interspecies differences can limit the translational value of excitable cells isolated from model organisms. It can be difficult to extrapolate from a drug- or mutation-induced phenotype in mice to human pathophysiology because mouse and human cardiac electrodynamics differ greatly. We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morphologies of any two cell types of interest. PMID:19917221

  12. Experimental and theoretical description of higher order periods in cardiac tissue action potential duration

    NASA Astrophysics Data System (ADS)

    Herndon, Conner; Fenton, Flavio; Uzelac, Ilija

    Much theoretical, experimental, and clinical research has been devoted to investigating the initiation of cardiac arrhythmias by alternans, the first period doubling bifurcation in the duration of cardiac action potentials. Although period doubling above alternans has been shown to exist in many mammalian hearts, little is understood about their emergence or behavior. There currently exists no physiologically correct theory or model that adequately describes and predicts their emergence in stimulated tissue. In this talk we present experimental data of period 2, 4, and 8 dynamics and a mathematical model that describes these bifurcations. This model extends current cell models through the addition of memory and includes spatiotemporal nonlinearities arising from cellular coupling by tissue heterogeneity.

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

    PubMed

    Lin, Jen-Wei

    2016-01-01

    Action potential (AP) propagation in presynaptic axons of the crayfish opener neuromuscular junction (NMJ) was investigated by simultaneously recording from a terminal varicosity and a proximal branch. Although orthodromically conducting APs could be recorded in terminals with amplitudes up to 70 mV, depolarizing steps in terminals to -20 mV or higher failed to fire APs. Patch-clamp recordings did detect Na(+) current (INa) in most terminals. The INa exhibited a high threshold and fast activation rate. Local perfusion of Na(+)-free saline showed that terminal INa contributed to AP waveform by slightly accelerating the rising phase and increasing the peak amplitude. These findings suggest that terminal INa functions to "touch up" but not to generate APs. PMID:26561611

  14. Trichloroethanol alters action potentials in a subgroup of primary sensory neurones.

    PubMed

    Gruss, Marco; Hempelmann, Gunter; Scholz, Andreas

    2002-05-01

    We investigated the effects of 2,2,2-trichloroethanol (TCE), the active metabolite of chloral hydrate, on large-conductance calcium-activated K+ channels (BKCa channels) of dorsal root ganglion (DRG) neurones. In outside-out patches, 2 and 5 mM TCE increased the open probability of BKCa channels to 1.7-fold and 2.8-fold of control, respectively. In 50% of the cells investigated (group A) the action potential (AP) was shortened reversibly by TCE by 20% and the whole-cell outward-current was increased by 44%. Both effects could be antagonized by iberiotoxin. In a second group of neurone (group B), TCE prolonged the AP duration. The effects of TCE in group A, which was 20-fold more potent than ethanol on BKCa channels and AP might contribute to the described analgesic effect of chloral hydrate. PMID:11997700

  15. Control of action potential propagation by intracellular Ca2+ in cultured rat dorsal root ganglion cells.

    PubMed Central

    Lüscher, C; Lipp, P; Lüscher, H R; Niggli, E

    1996-01-01

    1. To assess the role of intracellular Ca2+ in action potential (AP) propagation, whole-cell recordings of cultured dorsal root ganglion (DRG) cells were carried out while Ca2+ was simultaneously measured with a laser-scanning confocal microscope. 2. Flash photolytic liberation of a Ca2+ buffer during trains of APs which partly failed to invade the DRG cell body immediately lowered intracellular Ca2+ and restored safe AP propagation. Furthermore, the speed of the propagated AP was reduced considerably when intracellular Ca2+ was increased by flash photolysis of caged Ca2+. 3. Both results suggest that intracellular Ca2+ regulates the safety factor for AP propagation and may thus provide a control mechanism for synaptic integration, which acts pre- as well as postsynaptically. Images Figure 1 Figure 3 PMID:8821131

  16. Effect of Cardiac Tissue Anisotropy on Three-Dimensional Electrical Action Potential Propagation

    NASA Astrophysics Data System (ADS)

    He, Zhi Zhu; Liu, Jing

    A three-dimensional (3D) electrical action potential propagation model is developed to characterize the integrated effect of cardiac tissue structure using a homogenous function with a spatial inhomogeneity. This method may be more effective for bridging the gap between computational models and experimental data for cardiac tissue anisotropy. A generalized 3D eikonal relation considering anisotropy and a self-similar evolution solution of such a relation are derived to identify the effect of anisotropy and predict the anisotropy-induced electrical wave propagation instabilities. Furthermore, the phase field equation is introduced to obtain the complex three-dimensional numerical solution of the new correlation. The present results are expected to be valuable for better understanding the physiological behavior of cardiac tissues.

  17. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates

    PubMed Central

    Schlaepfer, Charles H.; Wessel, Ralf

    2015-01-01

    The ciliate Paramecium caudatum possesses an excitable cell membrane whose action potentials (APs) modulate the trajectory of the cell swimming through its freshwater environment. While many stimuli affect the membrane potential and trajectory, students can use current injection and extracellular ionic concentration changes to explore how APs cause reversal of the cell’s motion. Students examine these stimuli through intracellular recordings, also gaining insight into the practices of electrophysiology. Paramecium’s large size of around 150 µm, simple care, and relative ease to penetrate make them ideal model organisms for undergraduate students’ laboratory study. The direct link between behavior and excitable membranes has thought provoking evolutionary implications for the study of paramecia. Recording from the cell, students note a small resting potential around −30 mV, differing from animal resting potentials. By manipulating ion concentrations, APs of the relatively long length of 20–30 ms up to several minutes with depolarizations maxing over 0 mV are observed. Through comparative analysis of membrane potentials and the APs induced by either calcium or barium, students can deduce the causative ions for the APs as well as the mechanisms of paramecium APs. Current injection allows students to calculate quantitative electric characteristics of the membrane. Analysis will follow the literature’s conclusion in a V-Gated Ca++ influx and depolarization resulting in feedback from intracellular Ca++ that inactivates V-Gated Ca++ channels and activates Ca-Dependent K+ channels through a secondary messenger cascade that results in the K+ efflux and repolarization. PMID:26557800

  18. Removal of spike frequency adaptation via neuromodulation intrinsic to the Tritonia escape swim central pattern generator.

    PubMed

    Katz, P S; Frost, W N

    1997-10-15

    For the mollusc Tritonia diomedea to generate its escape swim motor pattern, interneuron C2, a crucial member of the central pattern generator (CPG) for this rhythmic behavior, must fire repetitive bursts of action potentials. Yet, before swimming, repeated depolarizing current pulses injected into C2 at periods similar those in the swim motor program are incapable of mimicking the firing rate attained by C2 on each cycle of a swim motor program. This resting level of C2 inexcitability is attributable to its own inherent spike frequency adaptation (SFA). Clearly, this property must be altered for the swim behavior to occur. The pathway for initiation of the swimming behavior involves activation of the serotonergic dorsal swim interneurons (DSIs), which are also intrinsic members of the swim CPG. Physiologically appropriate DSI stimulation transiently decreases C2 SFA, allowing C2 to fire at higher rates even when repeatedly depolarized at short intervals. The increased C2 excitability caused by DSI stimulation is mimicked and occluded by serotonin application. Furthermore, the change in excitability is not caused by the depolarization associated with DSI stimulation or serotonin application but is correlated with a decrease in C2 spike afterhyperpolarization. This suggests that the DSIs use serotonin to evoke a neuromodulatory action on a conductance in C2 that regulates its firing rate. This modulatory action of one CPG neuron on another is likely to play a role in configuring the swim circuit into its rhythmic pattern-generating mode and maintaining it in that state. PMID:9315892

  19. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials

    PubMed Central

    2012-01-01

    Background Modern cochlear implants have integrated recording systems for measuring electrically evoked compound action potentials of the auditory nerve. The characterization of such recording systems is important for establishing a reliable basis for the interpretation of signals acquired in vivo. In this study we investigated the characteristics of the recording system integrated into the MED-EL PULSARCI100 cochlear implant, especially its linearity and resolution, in order to develop a mathematical model describing the recording system. Methods In-vitro setup: The cochlear implant, including all attached electrodes, was fixed in a tank of physiologic saline solution. Sinusoidal signals of the same frequency but with different amplitudes were delivered via a signal generator for measuring and recording on a single electrode. Computer simulations: A basic mathematical model including the main elements of the recording system, i.e. amplification and digitalization stage, was developed. For this, digital output for sinusoidal input signals of different amplitudes were calculated using in-vitro recordings as reference. Results Using an averaging of 100 measurements the recording system behaved linearly down to approximately -60 dB of the input signal range. Using the same method, a system resolution of 10 μV was determined for sinusoidal signals. The simulation results were in very good agreement with the results obtained from in-vitro experiments. Conclusions The recording system implemented in the MED-EL PULSARCI100 cochlear implant for measuring the evoked compound action potential of the auditory nerve operates reliably. The developed mathematical model provides a good approximation of the recording system. PMID:22531599

  20. Mannan Oligosaccharides in Nursery Pig Nutrition and Their Potential Mode of Action

    PubMed Central

    Halas, Veronika; Nochta, Imre

    2012-01-01

    Simple Summary The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action. Mannan oligosaccharide products maintain intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period in pigs and enhance disease resistance by promoting antigen presentation. We find that dietary supplementation has growth promoting effects in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards. Abstract Mannan oligosaccharides (MOSs) are often referred to as one of the potential alternatives for antimicrobial growth promoters. The aim of the paper is to provide a review of mannan oligosaccharide products in relation to their growth promoting effect and mode of action based on the latest publications. We discuss the dietary impact of MOSs on (1) microbial changes, (2) morphological changes of gut tissue and digestibility of nutrients, and (3) immune response of pigs after weaning. Dietary MOSs maintain the intestinal integrity and the digestive and absorptive function of the gut in the post-weaning period. Recent results suggest that MOS enhances the disease resistance in swine by promoting antigen presentation facilitating thereby the shift from an innate to an adaptive immune response. Accordingly, dietary MOS supplementation has a potential growth promoting effect in pigs kept in a poor hygienic environment, while the positive effect of MOS is not observed in healthy pig herds with high hygienic standards that are able to maintain a high growth rate after weaning. PMID:26486920

  1. Glutamine and glutamate limit the shortening of action potential duration in anoxia-challenged rabbit hearts

    PubMed Central

    Drake, Kenneth J; Shotwell, Matthew S; Wikswo, John P; Sidorov, Veniamin Y

    2015-01-01

    In clinical conditions, amino acid supplementation is applied to improve contractile function, minimize ischemia/reperfusion injury, and facilitate postoperative recovery. It has been shown that glutamine enhances myocardial ATP/APD (action potential duration) and glutathione/oxidized glutathione ratios, and can increase hexosamine biosynthesis pathway flux, which is believed to play a role in cardioprotection. Here, we studied the effect of glutamine and glutamate on electrical activity in Langendorff-perfused rabbit hearts. The hearts were supplied by Tyrode's media with or without 2.5 mmol/L glutamine and 150 μmol/L glutamate, and exposed to two 6-min anoxias with 20-min recovery in between. Change in APD was detected using a monophasic action potential probe. A nonlinear mixed-effects regression technique was used to evaluate the effect of amino acids on APD over the experiment. Typically, the dynamic of APD change encompasses three phases: short transient increase (more prominent in the first episode), slow decrease, and fast increase (starting with the beginning of recovery). The effect of both anoxic challenge and glutamine/glutamate was cumulative, being more pronounced in the second anoxia. The amino acids' protective effect became largest by the end of anoxia – 20.0% (18.9, 95% CI: [2.6 ms, 35.1 ms]), during the first anoxia and 36.6% (27.1, 95% CI: [7.7 ms, 46.6 ms]), during the second. Following the second anoxia, APD difference between control and supplemented hearts progressively increased, attaining 10.8% (13.6, 95% CI: [4.1 ms, 23.1 ms]) at the experiments' end. Our data reveal APD stabilizing and suggest an antiarrhythmic capacity of amino acid supplementation in anoxic/ischemic conditions. PMID:26333831

  2. Sound Rhythms Are Encoded by Postinhibitory Rebound Spiking in the Superior Paraolivary Nucleus

    PubMed Central

    Felix, Richard A.; Fridberger, Anders; Leijon, Sara; Berrebi, Albert S.; Magnusson, Anna K.

    2013-01-01

    The superior paraolivary nucleus (SPON) is a prominent structure in the auditory brainstem. In contrast to the principal superior olivary nuclei with identified roles in processing binaural sound localization cues, the role of the SPON in hearing is not well understood. A combined in vitro and in vivo approach was used to investigate the cellular properties of SPON neurons in the mouse. Patch-clamp recordings in brain slices revealed that brief and well timed postinhibitory rebound spiking, generated by the interaction of two subthreshold-activated ion currents, is a hallmark of SPON neurons. The Ih current determines the timing of the rebound, whereas the T-type Ca2+ current boosts the rebound to spike threshold. This precisely timed rebound spiking provides a physiological explanation for the sensitivity of SPON neurons to sinusoidally amplitude-modulated (SAM) tones in vivo, where peaks in the sound envelope drive inhibitory inputs and SPON neurons fire action potentials during the waveform troughs. Consistent with this notion, SPON neurons display intrinsic tuning to frequency-modulated sinusoidal currents (1–15Hz) in vitro and discharge with strong synchrony to SAMs with modulation frequencies between 1 and 20 Hz in vivo. The results of this study suggest that the SPON is particularly well suited to encode rhythmic sound patterns. Such temporal periodicity information is likely important for detection of communication cues, such as the acoustic envelopes of animal vocalizations and speech signals. PMID:21880918

  3. Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli

    PubMed Central

    2012-01-01

    Background The next generation of prosthetic limbs will restore sensory feedback to the nervous system by mimicking how skin mechanoreceptors, innervated by afferents, produce trains of action potentials in response to compressive stimuli. Prior work has addressed building sensors within skin substitutes for robotics, modeling skin mechanics and neural dynamics of mechanotransduction, and predicting response timing of action potentials for vibration. The effort here is unique because it accounts for skin elasticity by measuring force within simulated skin, utilizes few free model parameters for parsimony, and separates parameter fitting and model validation. Additionally, the ramp-and-hold, sustained stimuli used in this work capture the essential features of the everyday task of contacting and holding an object. Methods This systems integration effort computationally replicates the neural firing behavior for a slowly adapting type I (SAI) afferent in its temporally varying response to both intensity and rate of indentation force by combining a physical force sensor, housed in a skin-like substrate, with a mathematical model of neuronal spiking, the leaky integrate-and-fire. Comparison experiments were then conducted using ramp-and-hold stimuli on both the spiking-sensor model and mouse SAI afferents. The model parameters were iteratively fit against recorded SAI interspike intervals (ISI) before validating the model to assess its performance. Results Model-predicted spike firing compares favorably with that observed for single SAI afferents. As indentation magnitude increases (1.2, 1.3, to 1.4 mm), mean ISI decreases from 98.81 ± 24.73, 54.52 ± 6.94, to 41.11 ± 6.11 ms. Moreover, as rate of ramp-up increases, ISI during ramp-up decreases from 21.85 ± 5.33, 19.98 ± 3.10, to 15.42 ± 2.41 ms. Considering first spikes, the predicted latencies exhibited a decreasing trend as stimulus rate increased, as is observed in afferent

  4. Learning Pitch with STDP: A Computational Model of Place and Temporal Pitch Perception Using Spiking Neural Networks.

    PubMed

    Erfanian Saeedi, Nafise; Blamey, Peter J; Burkitt, Anthony N; Grayden, David B

    2016-04-01

    Pitch perception is important for understanding speech prosody, music perception, recognizing tones in tonal languages, and perceiving speech in noisy environments. The two principal pitch perception theories consider the place of maximum neural excitation along the auditory nerve and the temporal pattern of the auditory neurons' action potentials (spikes) as pitch cues. This paper describes a biophysical mechanism by which fine-structure temporal information can be extracted from the spikes generated at the auditory periphery. Deriving meaningful pitch-related information from spike times requires neural structures specialized in capturing synchronous or correlated activity from amongst neural events. The emergence of such pitch-processing neural mechanisms is described through a computational model of auditory processing. Simulation results show that a correlation-based, unsupervised, spike-based form of Hebbian learning can explain the development of neural structures required for recognizing the pitch of simple and complex tones, with or without the fundamental frequency. The temporal code is robust to variations in the spectral shape of the signal and thus can explain the phenomenon of pitch constancy. PMID:27049657

  5. Learning Pitch with STDP: A Computational Model of Place and Temporal Pitch Perception Using Spiking Neural Networks

    PubMed Central

    Erfanian Saeedi, Nafise; Blamey, Peter J.; Burkitt, Anthony N.; Grayden, David B.

    2016-01-01

    Pitch perception is important for understanding speech prosody, music perception, recognizing tones in tonal languages, and perceiving speech in noisy environments. The two principal pitch perception theories consider the place of maximum neural excitation along the auditory nerve and the temporal pattern of the auditory neurons’ action potentials (spikes) as pitch cues. This paper describes a biophysical mechanism by which fine-structure temporal information can be extracted from the spikes generated at the auditory periphery. Deriving meaningful pitch-related information from spike times requires neural structures specialized in capturing synchronous or correlated activity from amongst neural events. The emergence of such pitch-processing neural mechanisms is described through a computational model of auditory processing. Simulation results show that a correlation-based, unsupervised, spike-based form of Hebbian learning can explain the development of neural structures required for recognizing the pitch of simple and complex tones, with or without the fundamental frequency. The temporal code is robust to variations in the spectral shape of the signal and thus can explain the phenomenon of pitch constancy. PMID:27049657

  6. Quantification of Transmembrane Currents during Action Potential Propagation in the Heart

    PubMed Central

    Gray, Richard A.; Mashburn, David N.; Sidorov, Veniamin Y.; Wikswo, John P.

    2013-01-01

    The measurement, quantitative analysis, theory, and mathematical modeling of transmembrane potential and currents have been an integral part of the field of electrophysiology since its inception. Biophysical modeling of action potential propagation begins with detailed ionic current models for a patch of membrane within a distributed cable model. Voltage-clamp techniques have revolutionized clinical electrophysiology via the characterization of the transmembrane current gating variables; however, this kinetic information alone is insufficient to accurately represent propagation. Other factors, including channel density, membrane area, surface/volume ratio, axial conductivities, etc., are also crucial determinants of transmembrane currents in multicellular tissue but are extremely difficult to measure. Here, we provide, to our knowledge, a novel analytical approach to compute transmembrane currents directly from experimental data, which involves high-temporal (200 kHz) recordings of intra- and extracellular potential with glass microelectrodes from the epicardial surface of isolated rabbit hearts during propagation. We show for the first time, to our knowledge, that during stable planar propagation the biphasic total transmembrane current (Im) dipole density during depolarization was ∼0.25 ms in duration and asymmetric in amplitude (peak outward current was ∼95 μA/cm2 and peak inward current was ∼140 μA/cm2), and the peak inward ionic current (Iion) during depolarization was ∼260 μA/cm2 with duration of ∼1.0 ms. Simulations of stable propagation using the ionic current versus transmembrane potential relationship fit from the experimental data reproduced these values better than traditional ionic models. During ventricular fibrillation, peak Im was decreased by 50% and peak Iion was decreased by 70%. Our results provide, to our knowledge, novel quantitative information that complements voltage- and patch-clamp data. PMID:23332079

  7. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

    PubMed Central

    Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

    2012-01-01

    Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

  8. Regulation of action potential delays via voltage-gated potassium Kv1.1 channels in dentate granule cells during hippocampal epilepsy

    PubMed Central

    Kirchheim, Florian; Tinnes, Stefanie; Haas, Carola A.; Stegen, Michael; Wolfart, Jakob

    2013-01-01

    Action potential (AP) responses of dentate gyrus granule (DG) cells have to be tightly regulated to maintain hippocampal function. However, which ion channels control the response delay of DG cells is not known. In some neuron types, spike latency is influenced by a dendrotoxin (DTX)-sensitive delay current (ID) mediated by unidentified combinations of voltage-gated K+ (Kv) channels of the Kv1 family Kv1.1–6. In DG cells, the ID has not been characterized and its molecular basis is unknown. The response phenotype of mature DG cells is usually considered homogenous but intrinsic plasticity likely occurs in particular in conditions of hyperexcitability, for example during temporal lobe epilepsy (TLE). In this study, we examined response delays of DG cells and underlying ion channel molecules by employing a combination of gramicidin-perforated patch-clamp recordings in acute brain slices and single-cell reverse transcriptase quantitative polymerase chain reaction (SC RT-qPCR) experiments. An in vivo mouse model of TLE consisting of intrahippocampal kainate (KA) injection was used to examine epilepsy-related plasticity. Response delays of DG cells were DTX-sensitive and strongly increased in KA-injected hippocampi; Kv1.1 mRNA was elevated 10-fold, and the response delays correlated with Kv1.1 mRNA abundance on the single cell level. Other Kv1 subunits did not show overt changes in mRNA levels. Kv1.1 immunolabeling was enhanced in KA DG cells. The biophysical properties of ID and a delay heterogeneity within the DG cell population was characterized. Using organotypic hippocampal slice cultures (OHCs), where KA incubation also induced ID upregulation, the homeostatic reversibility and neuroprotective potential for DG cells were tested. In summary, the AP timing of DG cells is effectively controlled via scaling of Kv1.1 subunit transcription. With this antiepileptic mechanism, DG cells delay their responses during hyperexcitation. PMID:24367293

  9. Simultaneous Optical Mapping of Intracellular Free Calcium and Action Potentials from Langendorff Perfused Hearts

    PubMed Central

    Salama, Guy; Hwang, Seong-min

    2015-01-01

    The cardiac action potential (AP) controls the rise and fall of intracellular free Ca2+ (Cai), and thus the amplitude and kinetics of force generation. Besides excitation-contraction coupling, the reverse process where Cai influences the AP through Cai-dependent ionic currents has been implicated as the mechanism underlying QT alternans and cardiac arrhythmias in heart failure, ischemia/reperfusion, cardiac myopathy, myocardial infarction, congenital and drug-induced long QT syndrome, and ventricular fibrillation. The development of dual optical mapping at high spatial and temporal resolution provides a powerful tool to investigate the role of Cai anomalies in eliciting cardiac arrhythmias. This unit describes experimental protocols to map APs and Cai transients from perfused hearts by labeling the heart with two fluorescent dyes, one to measure transmembrane potential (Vm), the other Cai transients. High spatial and temporal resolution is achieved by selecting Vm and Cai probes with the same excitation but different emission wavelengths, to avoid cross-talk and mechanical components. PMID:19575468

  10. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    NASA Astrophysics Data System (ADS)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  11. 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

    2016-01-01

    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. PMID:27510732

  12. Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells.

    PubMed

    Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie

    2016-01-01

    Electrophysiological variability in cardiomyocytes derived from pluripotent stem cells continues to be an impediment for their scientific and translational applications. We studied the variability of action potentials (APs) recorded from clusters of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using high-resolution optical mapping. Over 23,000 APs were analyzed through four parameters: APD30, APD80, triangulation and fractional repolarization. Although measures were taken to reduce variability due to cell culture conditions and rate-dependency of APs, we still observed significant variability in APs among and within the clusters. However, similar APs were found in spatial locations with close proximity, and in some clusters formed distinct regions having different AP characteristics that were reflected as separate peaks in the AP parameter distributions, suggesting multiple electrophysiological phenotypes. Using a recently developed automated method to group cells based on their entire AP shape, we identified distinct regions of different phenotypes within single clusters and common phenotypes across different clusters when separating APs into 2 or 3 subpopulations. The systematic analysis of the heterogeneity and potential phenotypes of large populations of hESC-CMs can be used to evaluate strategies to improve the quality of pluripotent stem cell-derived cardiomyocytes for use in diagnostic and therapeutic applications and in drug screening. PMID:26729331

  13. Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

    PubMed Central

    Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

    2016-01-01

    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. PMID:27510732

  14. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    PubMed Central

    Spencer, C. Ian; Baba, Shiro; Nakamura, Kenta; Hua, Ethan A.; Sears, Marie A.F.; Fu, Chi-cheng; Zhang, Jianhua; Balijepalli, Sadguna; Tomoda, Kiichiro; Hayashi, Yohei; Lizarraga, Paweena; Wojciak, Julianne; Scheinman, Melvin M.; Aalto-Setälä, Katriina; Makielski, Jonathan C.; January, Craig T.; Healy, Kevin E.; Kamp, Timothy J.; Yamanaka, Shinya; Conklin, Bruce R.

    2014-01-01

    Summary Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP). Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i) measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM). In myocytes carrying an LQT2 mutation (HERG-A422T), APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site. PMID:25254341

  15. Detection of M-sequences from spike sequence in neuronal networks.

    PubMed

    Nishitani, Yoshi; Hosokawa, Chie; Mizuno-Matsumoto, Yuko; Miyoshi, Tomomitsu; Sawai, Hajime; Tamura, Shinichi

    2012-01-01

    In circuit theory, it is well known that a linear feedback shift register (LFSR) circuit generates pseudorandom bit sequences (PRBS), including an M-sequence with the maximum period of length. In this study, we tried to detect M-sequences known as a pseudorandom sequence generated by the LFSR circuit from time series patterns of stimulated action potentials. Stimulated action potentials were recorded from dissociated cultures of hippocampal neurons grown on a multielectrode array. We could find several M-sequences from a 3-stage LFSR circuit (M3). These results show the possibility of assembling LFSR circuits or its equivalent ones in a neuronal network. However, since the M3 pattern was composed of only four spike intervals, the possibility of an accidental detection was not zero. Then, we detected M-sequences from random spike sequences which were not generated from an LFSR circuit and compare the result with the number of M-sequences from the originally observed raster data. As a result, a significant difference was confirmed: a greater number of "0-1" reversed the 3-stage M-sequences occurred than would have accidentally be detected. This result suggests that some LFSR equivalent circuits are assembled in neuronal networks. PMID:22851966

  16. Detection of M-Sequences from Spike Sequence in Neuronal Networks

    PubMed Central

    Nishitani, Yoshi; Hosokawa, Chie; Mizuno-Matsumoto, Yuko; Miyoshi, Tomomitsu; Sawai, Hajime; Tamura, Shinichi

    2012-01-01

    In circuit theory, it is well known that a linear feedback shift register (LFSR) circuit generates pseudorandom bit sequences (PRBS), including an M-sequence with the maximum period of length. In this study, we tried to detect M-sequences known as a pseudorandom sequence generated by the LFSR circuit from time series patterns of stimulated action potentials. Stimulated action potentials were recorded from dissociated cultures of hippocampal neurons grown on a multielectrode array. We could find several M-sequences from a 3-stage LFSR circuit (M3). These results show the possibility of assembling LFSR circuits or its equivalent ones in a neuronal network. However, since the M3 pattern was composed of only four spike intervals, the possibility of an accidental detection was not zero. Then, we detected M-sequences from random spike sequences which were not generated from an LFSR circuit and compare the result with the number of M-sequences from the originally observed raster data. As a result, a significant difference was confirmed: a greater number of “0–1” reversed the 3-stage M-sequences occurred than would have accidentally be detected. This result suggests that some LFSR equivalent circuits are assembled in neuronal networks. PMID:22851966

  17. Learning Universal Computations with Spikes

    PubMed Central

    Thalmeier, Dominik; Uhlmann, Marvin; Kappen, Hilbert J.; Memmesheimer, Raoul-Martin

    2016-01-01

    Providing the neurobiological basis of information processing in higher animals, spiking neural networks must be able to learn a variety of complicated computations, including the generation of appropriate, possibly delayed reactions to inputs and the self-sustained generation of complex activity patterns, e.g. for locomotion. Many such computations require previous building of intrinsic world models. Here we show how spiking neural networks may solve these different tasks. Firstly, we derive constraints under which classes of spiking neural networks lend themselves to substrates of powerful general purpose computing. The networks contain dendritic or synaptic nonlinearities and have a constrained connectivity. We then combine such networks with learning rules for outputs or recurrent connections. We show that this allows to learn even difficult benchmark tasks such as the self-sustained generation of desired low-dimensional chaotic dynamics or memory-dependent computations. Furthermore, we show how spiking networks can build models of external world systems and use the acquired knowledge to control them. PMID:27309381

  18. Designing optimal stimuli to control neuronal spike timing.

    PubMed

    Ahmadian, Yashar; Packer, Adam M; Yuste, Rafael; Paninski, Liam

    2011-08-01

    Recent advances in experimental stimulation methods have raised the following important computational question: how can we choose a stimulus that will drive a neuron to output a target spike train with optimal precision, given physiological constraints? Here we adopt an approach based on models that describe how a stimulating agent (such as an injected electrical current or a laser light interacting with caged neurotransmitters or photosensitive ion channels) affects the spiking activity of neurons. Based on these models, we solve the reverse problem of finding the best time-dependent modulation of the input, subject to hardware limitations as well as physiologically inspired safety measures, that causes the neuron to emit a spike train that with highest probability will be close to a target spike train. We adopt fast convex constrained optimization methods to solve this problem. Our methods can potentially be implemented in real time and may also be generalized to the case of many cells, suitable for neural prosthesis applications. With the use of biologically sensible parameters and constraints, our method finds stimulation patterns that generate very precise spike trains in simulated experiments. We also tested the intracellular current injection method on pyramidal cells in mouse cortical slices, quantifying the dependence of spiking reliability and timing precision on constraints imposed on the applied currents. PMID:21511704

  19. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    PubMed

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  20. Bursts shape the NMDA-R mediated spike timing dependent plasticity curve: role of burst interspike interval and GABAergic inhibition.

    PubMed

    Cutsuridis, Vassilis

    2012-10-01

    Spike timing dependent plasticity (STDP) is a synaptic learning rule where the relative timing between the presynaptic and postsynaptic action potentials determines the sign and strength of synaptic plasticity. In its basic form STDP has an asymmetric form which incorporates both persistent increases and persistent decreases in synaptic strength. The basic form of STDP, however, is not a fixed property and depends on the dendritic location. An asymmetric curve is observed in the distal dendrites, whereas a symmetrical one is observed in the proximal ones. A recent computational study has shown that the transition from the asymmetry to symmetry is due to inhibition under certain conditions. Synapses have also been observed to be unreliable at generating plasticity when excitatory postsynaptic potentials and single spikes are paired at low frequencies. Bursts of spikes, however, are reliably signaled because transmitter release is facilitated. This article presents a two-compartment model of the CA1 pyramidal cell. The model is neurophysiologically plausible with its dynamics resulting from the interplay of many ionic and synaptic currents. Plasticity is measured by a deterministic Ca(2+) dynamics model which measures the instantaneous calcium level and its time course in the dendrite and change the strength of the synapse accordingly. The model is validated to match the asymmetrical form of STDP from the pairing of a presynaptic (dendritic) and postsynaptic (somatic) spikes as observed experimentally. With the parameter set unchanged the model investigates how pairing of bursts with single spikes and bursts in the presence or absence of inhibition shapes the STDP curve. The model predicts that inhibition strength and frequency are not the only factors of the asymmetry-to-symmetry switch of the STDP curve. Burst interspike interval is another factor. This study is an important first step towards understanding how STDP is affected under natural firing patterns in vivo

  1. Averaging methods for extracting representative waveforms from motor unit action potential trains.

    PubMed

    Malanda, Armando; Navallas, Javier; Rodriguez-Falces, Javier; Rodriguez-Carreño, Ignacio; Gila, Luis

    2015-08-01

    In the context of quantitative electromyography (EMG), it is of major interest to obtain a waveform that faithfully represents the set of potentials that constitute a motor unit action potential (MUAP) train. From this waveform, various parameters can be determined in order to characterize the MUAP for diagnostic analysis. The aim of this work was to conduct a thorough, in-depth review, evaluation and comparison of state-of-the-art methods for composing waveforms representative of MUAP trains. We evaluated nine averaging methods: Ensemble (EA), Median (MA), Weighted (WA), Five-closest (FCA), MultiMUP (MMA), Split-sweep median (SSMA), Sorted (SA), Trimmed (TA) and Robust (RA) in terms of three general-purpose signal processing figures of merit (SPMF) and seven clinically-used MUAP waveform parameters (MWP). The convergence rate of the methods was assessed as the number of potentials per MUAP train (NPM) required to reach a level of performance that was not significantly improved by increasing this number. Test material comprised 78 MUAP trains obtained from the tibialis anterioris of seven healthy subjects. Error measurements related to all SPMF and MWP parameters except MUAP amplitude descended asymptotically with increasing NPM for all methods. MUAP amplitude showed a consistent bias (around 4% for EA and SA and 1-2% for the rest). MA, TA and SSMA had the lowest SPMF and MWP error figures. Therefore, these methods most accurately preserve and represent MUAP physiological information of utility in clinical medical practice. The other methods, particularly WA, performed noticeably worse. Convergence rate was similar for all methods, with NPM values averaged among the nine methods, which ranged from 10 to 40, depending on the waveform parameter evaluated. PMID:25962870

  2. Probabilistic Decision Making with Spikes: From ISI Distributions to Behaviour via Information Gain

    PubMed Central

    Caballero, Javier A.; Lepora, Nathan F.; Gurney, Kevin N.

    2015-01-01

    Computational theories of decision making in the brain usually assume that sensory 'evidence' is accumulated supporting a number of hypotheses, and that the first accumulator to reach threshold triggers a decision in favour of its associated hypothesis. However, the evidence is often assumed to occur as a continuous process whose origins are somewhat abstract, with no direct link to the neural signals - action potentials or 'spikes' - that must ultimately form the substrate for decision making in the brain. Here we introduce a new variant of the well-known multi-hypothesis sequential probability ratio test (MSPRT) for decision making whose evidence observations consist of the basic unit of neural signalling - the inter-spike interval (ISI) - and which is based on a new form of the likelihood function. We dub this mechanism s-MSPRT and show its precise form for a range of realistic ISI distributions with positive support. In this way we show that, at the level of spikes, the refractory period may actually facilitate shorter decision times, and that the mechanism is robust against poor choice of the hypothesized data distribution. We show that s-MSPRT performance is related to the Kullback-Leibler divergence (KLD) or information gain between ISI distributions, through which we are able to link neural signalling to psychophysical observation at the behavioural level. Thus, we find the mean information needed for a decision is constant, thereby offering an account of Hick's law (relating decision time to the number of choices). Further, the mean decision time of s-MSPRT shows a power law dependence on the KLD offering an account of Piéron's law (relating reaction time to stimulus intensity). These results show the foundations for a research programme in which spike train analysis can be made the basis for predictions about behavior in multi-alternative choice tasks. PMID:25923907

  3. Novel Transabdominal Motor Action Potential (TaMAP) Neuromonitoring System for Spinal Surgery

    PubMed Central

    Feldman, Erica; Gabel, Brandon C; Taylor, Natalie; Gharib, James; Lee, Yu-Po; Taylor, William

    2016-01-01

    Introduction Minimally invasive lateral lumbar interbody fusion (LLIF) approaches to the lumbar spine reduce patient morbidity compared to anterior or posterior alternatives. This approach, however, decreases direct anatomical visualization, creating the need for highly sensitive and specific neurophysiological monitoring. We seek to determine feasibility in 'transabdominal motor action potential (TaMAP)' monitoring as an assessment for the integrity of the neural elements during lateral-approach surgeries to the lumbar spine.  Methods Cathode and anode leads were placed on the posterior and anterior surfaces of two porcine subjects. Currents of varying degrees were transmitted across, from front to back. Motor responses were monitored and recorded by needle electrodes in specific distal muscle groups of the lower extremity. Lastly, the cathode and anode were placed anterior and posterior to the chest wall and stimulated to the maximum of 1500 mA to determine any effect on cardiac rhythm. Results Responses were seen by measuring vertical height differences between peaks of corresponding evoked potentials. Recruitment began at 200 mA in the lower extremities. Stimulation at 450 mA recruited a reliable and distinguishable electrographic response from most muscle groups. Responses were recorded and reliably measured and increased in proportion to the graduation of transabdominal stimulation current; no responses were seen in the arms or face. 1500 mA across the chest wall failed to stimulate or induce cardiac arrhythmia on repeated stimulation, indicating safety of stimulation. Conclusion TaMAPs seen in the animal model provide a potential alternative to standard transcranial motor evoked potentials done in the lateral approach of LLIFs. TaMAP recordings in most muscle groups were recordable and reliable, though some muscle groups failed to stimulate. Safety of transabdominal motor evoked potentials was confirmed in this porcine study. Future studies

  4. An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

    NASA Astrophysics Data System (ADS)

    Kim, Hojeong; Sandercock, Thomas G.; Heckman, C. J.

    2015-08-01

    Objective. The goal of this study was to develop a physiologically plausible, computationally robust model for muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach. The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of three compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results. The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance. This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations.

  5. An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

    PubMed Central

    Kim, Hojeong; Sandercock, Thomas G.; Heckman, C. J.

    2016-01-01

    Objective The goal of this study was to develop a physiologically plausible, computationally robust model for the muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of 3 compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations. PMID:26087477

  6. Action Potentials are required for nitric oxide dependent LTP in CA1 neurons of adult GluR1 knockout and Wild-type mice

    PubMed Central

    Phillips, Keith G.; Hardingham, Neil R.; Fox, Kevin

    2009-01-01

    Neocortical LTP consists of both pre- and postsynaptic components that rely on nitric oxide (NO) and GluR1 respectively. In this study, we found that hippocampal LTP, induced by theta-burst stimulation in mature (> 8 week old) GluR1 knockout mice was almost entirely NO-dependent and involved both the α splice variant of NO synthase-1 (αNOS-1) and the NO synthase-3 (NOS-3) isoforms of NO synthase. Theta-burst induced LTP was also partly NO-dependent in wild-type mice, and made up approximately 50% of the potentiation 2 hours post-tetanus. Theta-burst stimulation reliably produced postsynaptic spikes including a high probability of complex spikes. Inhibition of postsynaptic somatic spikes with intracellular QX314 or local TTX application prevented LTP in the GluR1 knockout mice and also blocked the NO-component of LTP in wild-types. We conclude that theta-burst stimulation is particularly well suited to producing the somatic postsynaptic spikes required for NO-dependent LTP. PMID:19109486

  7. Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

    PubMed Central

    Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

    2008-01-01

    The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

  8. Antifungal potential of Sideroxylon obtusifolium and Syzygium cumini and their mode of action against Candida albicans.

    PubMed

    Pereira, Jozinete Vieira; Freires, Irlan Almeida; Castilho, Aline Rogéria; da Cunha, Marcos Guilherme; Alves, Harley da Silva; Rosalen, Pedro Luiz

    2016-10-01

    Context The emergence of resistant pathogens and toxicity of antifungals have encouraged an active search for novel candidates to manage Candida biofilms. Objective In this study, the little known species Sideroxylon obtusifolium T.D. Penn (Sapotacea) and Syzygium cumini (L.) Skeels (Myrtaceae), from the Caatinga biome in Brazil were chemically characterized and explored for their antifungal potential against C. albicans. Materials and methods We determined the effects of hydroalcoholic extracts/fractions upon fungal growth (minimum inhibitory and fungicidal concentrations, MIC/MFC), biofilm morphology (scanning electron microscopy) and viability (confocal laser scanning microscopy), proposed their mode of action (sorbitol and ergosterol assays), and finally investigated their effects against macrophage and keratinocyte cells in a cell-based assay. Data were analysed using one-way analysis of variance with Tukey-Kramer post-test (α = 0.05). Results The n-butanol (Nb) fraction from S. obtusifolium and S. cumini extract (Sc) showed flavonoids (39.11 ± 6.62 mg/g) and saponins (820.35 ± 225.38 mg/g), respectively, in their chemical composition and demonstrated antifungal activity, with MICs of 62.5 and 125 μg/mL, respectively. Nb and Sc may complex with ergosterol as there was a 4-16-fold increase in MICs in the presence of exogenous ergosterol, leading to disrupted permeability of cell membrane. Deleterious effects were observed on morphology and viability of treated biofilms from concentrations as low as their MICs and higher. Sc was not toxic to macrophages and keratinocytes at these concentrations (p > 0.05), unlike Nb. Conclusions Nb and Sc demonstrated considerable antifungal activity and should be further investigated as potential alternative candidates to treat Candida biofilms. PMID:26987037

  9. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    PubMed

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-01

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. PMID:26804557

  10. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake

    PubMed Central

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D.; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A.S.; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-01-01

    Summary Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant. Video Abstract PMID:26804557

  11. Action potential amplitude as a noninvasive indicator of motor unit-specific hypertrophy.

    PubMed

    Pope, Zachary K; Hester, Garrett M; Benik, Franklin M; DeFreitas, Jason M

    2016-05-01

    Skeletal muscle fibers hypertrophy in response to strength training, with type II fibers generally demonstrating the greatest plasticity in regards to cross-sectional area (CSA). However, assessing fiber type-specific CSA in humans requires invasive muscle biopsies. With advancements in the decomposition of surface electromyographic (sEMG) signals recorded using multichannel electrode arrays, the firing properties of individual motor units (MUs) can now be detected noninvasively. Since action potential amplitude (APSIZE) has a documented relationship with muscle fiber size, as well as with its parent MU's recruitment threshold (RT) force, our purpose was to examine if MU APSIZE, as a function of its RT (i.e., the size principle), could potentially be used as a longitudinal indicator of MU-specific hypertrophy. By decomposing the sEMG signals from the vastus lateralis muscle of 10 subjects during maximal voluntary knee extensions, we noninvasively assessed the relationship between MU APSIZE and RT before and immediately after an 8-wk strength training intervention. In addition to significant increases in muscle size and strength (P < 0.02), our data show that training elicited an increase in MU APSIZE of high-threshold MUs. Additionally, a large portion of the variance (83.6%) in the change in each individual's relationship between MU APSIZE and RT was explained by training-induced changes in whole muscle CSA (obtained via ultrasonography). Our findings suggest that the noninvasive, electrophysiological assessment of longitudinal changes to MU APSIZE appears to reflect hypertrophy specific to MUs across the RT continuum. PMID:26936975

  12. Wavelet Transform for Real-Time Detection of Action Potentials in Neural Signals

    PubMed Central

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold. PMID:21811455

  13. Dopaminergic modulation of axonal potassium channels and action potential waveform in pyramidal neurons of prefrontal cortex.

    PubMed

    Yang, Jing; Ye, Mingyu; Tian, Cuiping; Yang, Mingpo; Wang, Yonghong; Shu, Yousheng

    2013-07-01

    Voltage-gated K(+) (KV) channels play critical roles in shaping neuronal signals. KV channels distributed in the perisomatic regions and thick dendrites of cortical pyramidal neurons have been extensively studied. However, the properties and regulation of KV channels distributed in the thin axons remain unknown. In this study, by performing somatic and axonal patch-clamp recordings from layer 5 pyramidal neurons of prefrontal cortical slices, we showed that the rapidly inactivating A-currents mediated the transient K(+) currents evoked by action potential (AP) waveform command (KAP) at the soma, whereas the rapidly activating but slowly inactivating KV1-mediated D-currents dominated the KAP at the axon. In addition, activation of D1-like receptors for dopamine decreased the axonal K(+) currents, as a result of an increase in the activity of cAMP-PKA pathway. In contrast, activation of D2-like receptors showed an opposite effect on the axonal K(+) currents. Further experiments demonstrated that functional D1-like receptors were expressed at the main axon trunk and their activation could broaden the waveforms of axonal APs. Together, these results show that axonal KV channels were subjected to dopamine modulation, and this modulation could regulate the waveforms of propagating APs at the axon, suggesting an important role of dopaminergic modulation of axonal KV channels in regulating neuronal signalling. PMID:23568892

  14. Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action.

    PubMed

    Dutt, Vikas; Gupta, Sanjeev; Dabur, Rajesh; Injeti, Elisha; Mittal, Ashwani

    2015-09-01

    Over the last two decades, new insights into the etiology of skeletal muscle wasting/atrophy under diverse clinical settings including denervation, AIDS, cancer, diabetes, and chronic heart failure have been reported in the literature. However, the treatment of skeletal muscle wasting remains an unresolved challenge to this day. About nineteen potential drugs that can regulate loss of muscle mass have been reported in the literature. This paper reviews the mechanisms of action of all these drugs by broadly classifying them into six different categories. Mechanistic data of these drugs illustrate that they regulate skeletal muscle loss either by down-regulating myostatin, cyclooxygenase2, pro-inflammatory cytokines mediated catabolic wasting or by up-regulating cyclic AMP, peroxisome proliferator-activated receptor gamma coactivator-1α, growth hormone/insulin-like growth factor1, phosphatidylinositide 3-kinases/protein kinase B(Akt) mediated anabolic pathways. So far, five major proteolytic systems that regulate loss of muscle mass have been identified, but the majority of these drugs control only two or three proteolytic systems. In addition to their beneficial effect on restoring the muscle loss, many of these drugs show some level of toxicity and unwanted side effects such as dizziness, hypertension, and constipation. Therefore, further research is needed to understand and develop treatment strategies for muscle wasting. For successful management of skeletal muscle wasting either therapeutic agent which regulates all five known proteolytic systems or new molecular targets/proteolytic systems must be identified. PMID:26048279

  15. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    PubMed

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  16. Kv3.1 uses a timely resurgent K+ current to secure action potential repolarization

    PubMed Central

    Labro, Alain J.; Priest, Michael F.; Lacroix, Jérôme J.; Snyders, Dirk J.; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K+ currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na+ and K+ currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3–S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  17. Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

    PubMed Central

    van der Velden, V H

    1998-01-01

    GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized. PMID:9792333

  18. Do Resin Cements Alter Action Potentials of Isolated Rat Sciatic Nerve?

    PubMed Central

    Ertan, Ahmet Atila; Beriat, Nilufer Celebi; Onur, Mehmet Ali; Tan, Gamze; Cehreli, Murat Cavit

    2011-01-01

    Objectives: The purpose of this study was to explore the effects dual-cure resin cements on nerve conduction. Methods: Panavia F, RelyX ARC, and Variolink II polymerized either by light-emitting diode (LED) or quartz tungsten halogen (QTH) were used in the study (n=10). The conductance of sciatic nerves of 50 rats were measured before and after contact with the specimens for 1 h. Results: The time-dependent change in nerve conductance and the comparison of LED versus QTH showed that differences between groups are significant (P<.05). For both polymerization techniques, pair-wise comparisons of resin cements showed that the nerve conductance between groups is different (P<.05). RelyX ARC elicited irreversible inhibition of compound action potentials (more than 50% change) and Panavia F and Variolink II polymerized by LED and QTH did not alter nerve conduction beyond physiologic limits. Conclusions: Resin cements may alter nerve conductance and even lead to neurotoxic effects. PMID:21494389

  19. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    SciTech Connect

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

  20. A novel analysis of excitatory currents during an action potential from suprachiasmatic nucleus neurons

    PubMed Central

    2013-01-01

    A new application of the action potential (AP) voltage-clamp technique is described based on computational analysis. An experimentally recorded AP is digitized. The resulting Vi vs. ti data set is applied to mathematical models of the ionic conductances underlying excitability for the cell from which the AP was recorded to test model validity. The method is illustrated for APs from suprachiasmatic nucleus (SCN) neurons and the underlying tetrodotoxin-sensitive Na+ current, INa, and the Ca2+ current, ICa. Voltage-step recordings have been made for both components from SCN neurons (Jackson et al. 2004). The combination of voltage-step and AP clamp results provides richer constraints for mathematical models of voltage-gated ionic conductances than either set of results alone, in particular the voltage-step results. For SCN neurons the long-term goal of this work is a realistic mathematical model of the SCN AP in which the equations for INa and ICa obtained from this analysis will be a part. Moreover, the method described in this report is general. It can be applied to any excitable cell. PMID:24047903

  1. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    PubMed

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B; Niven, Jeremy E

    2010-01-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+) and K(+) currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+) and K(+) channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

  2. Motor Unit Number Estimation and Motor Unit Action Potential Analysis in Carpal Tunnel Syndrome

    PubMed Central

    Sohn, Min Kyun; Jee, Sung Ju; Kim, Young-Jae; Shin, Hyun-Dae

    2011-01-01

    Objective To evaluate the clinical significance of motor unit number estimation (MUNE) and quantitative analysis of motor unit action potential (MUAP) in carpal tunnel syndrome (CTS) according to electrophysiologic severity, ultrasonographic measurement and clinical symptoms. Method We evaluated 78 wrists of 45 patients, who had been diagnosed with CTS and 42 wrists of 21 healthy controls. Median nerve conduction studies, amplitude and duration of MUAP, and the MUNE of the abductor pollicis brevis were measured. The cross sectional area (CSA) of the median nerve at the pisiform and distal radioulnar joint level was determined by high resolution ultrasonography. Clinical symptom of CTS was assessed using the Boston Carpal Tunnel Questionnaire (BCTQ). Results The MUNE, the amplitude and the duration of MUAP of the CTS group were significantly different from those found in the control group. The area under the ROC curve was 0.944 for MUNE, 0.923 for MUAP amplitude and 0.953 for MUAP duration. MUNE had a negative correlation with electrophysiologic stage of CTS, amplitude and duration of MUAP, CSA at pisiform level, and the score of BCTQ. The amplitude and duration of MUAP had a positive correlation with the score of BCTQ. The electrophysiologic stage was correlated with amplitude but not with the duration of MUAP. Conclusion MUNE, amplitude and duration of MUAP are useful tests for diagnosis of CTS. In addition, the MUNE serves as a good indicator of CTS severity. PMID:22506210

  3. Efficacy of action potential simulation and interferential therapy in the rehabilitation of patients with knee osteoarthritis

    PubMed Central

    Eftekharsadat, Bina; Habibzadeh, Afshin; Kolahi, Babak

    2015-01-01

    Objective: Knee osteoarthritis (OA) is the main cause of pain, physical impairment and chronic disability in older people. Electrotherapeutic modalities such as interferential therapy (IFT) and action potential simulation (APS) are used for the treatment of knee OA. In this study, we aim to evaluate the therapeutic effects of APS and IFT on knee OA. Methods: In this randomized clinical trial, 67 patients (94% female and 6% male with mean age of 52.80 ± 8.16 years) with mild and moderate knee OA were randomly assigned to be treated with APS (n = 34) or IFT (n = 33) for 10 sessions in 4 weeks. Baseline and post-treatment Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales, visual analogue scale (VAS) and timed up and go (TUG) test were measured in all patients. Results: VAS and WOMAC subscales were significantly improved after treatment in APS and IFT groups (p < 0.001 for all). TUG was also significantly improved after treatment in APS group (p < 0.001), but TUG changes in IFT was not significant (p = 0.09). There was no significant difference in VAS, TUG and WOMAC subscales values before and after treatment as well as the mean improvement in VAS, TUG and WOMAC subscales during study between groups. Conclusion: Short-term treatment with both APS and IFT could significantly reduce pain and improve physical function in patients with knee OA. PMID:26029268

  4. Variety of the Wave Change in Compound Muscle Action Potential in an Animal Model

    PubMed Central

    Ito, Zenya; Ando, Kei; Muramoto, Akio; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Tsushima, Mikito; Matsumoto, Akiyuki; Tanaka, Satoshi; Morozumi, Masayoshi; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    Study Design Animal study. Purpose To review the present warning point criteria of the compound muscle action potential (CMAP) and investigate new criteria for spinal surgery safety using an animal model. Overview of Literature Little is known about correlation palesis and amplitude of spinal cord monitoring. Methods After laminectomy of the tenth thoracic spinal lamina, 2-140 g force was delivered to the spinal cord with a tension gage to create a bilateral contusion injury. The study morphology change of the CMAP wave and locomotor scale were evaluated for one month. Results Four different types of wave morphology changes were observed: no change, amplitude decrease only, morphology change only, and amplitude and morphology change. Amplitude and morphology changed simultaneously and significantly as the injury force increased (p<0.05) Locomotor scale in the amplitude and morphology group worsened more than the other groups. Conclusions Amplitude and morphology change of the CMAP wave exists and could be the key of the alarm point in CMAP. PMID:26713129

  5. Action potential generation in an anatomically constrained model of medial superior olive axons.

    PubMed

    Lehnert, Simon; Ford, Marc C; Alexandrova, Olga; Hellmundt, Franziska; Felmy, Felix; Grothe, Benedikt; Leibold, Christian

    2014-04-01

    Neurons in the medial superior olive (MSO) encode interaural time differences (ITDs) with sustained firing rates of >100 Hz. They are able to generate such high firing rates for several hundred milliseconds despite their extremely low-input resistances of only few megaohms and high synaptic conductances in vivo. The biophysical mechanisms by which these leaky neurons maintain their excitability are not understood. Since action potentials (APs) are usually assumed to be generated in the axon initial segment (AIS), we analyzed anatomical data of proximal MSO axons in Mongolian gerbils and found that the axon diameter is <1 μm and the internode length is ∼100 μm. Using a morphologically constrained computational model of the MSO axon, we show that these thin axons facilitate the excitability of the AIS. However, for ongoing high rates of synaptic inputs the model generates a substantial fraction of APs in its nodes of Ranvier. These distally initiated APs are mediated by a spatial gradient of sodium channel inactivation and a strong somatic current sink. The model also predicts that distal AP initiation increases the dynamic range of the rate code for ITDs. PMID:24719114

  6. Mechanism of Action of IL-7 and Its Potential Applications and Limitations in Cancer Immunotherapy

    PubMed Central

    Gao, Jianbao; Zhao, Lintao; Wan, Yisong Y.; Zhu, Bo

    2015-01-01

    Interleukin-7 (IL-7) is a non-hematopoietic cell-derived cytokine with a central role in the adaptive immune system. It promotes lymphocyte development in the thymus and maintains survival of naive and memory T cell homeostasis in the periphery. Moreover, it is important for the organogenesis of lymph nodes (LN) and for the maintenance of activated T cells recruited into the secondary lymphoid organs (SLOs). The immune capacity of cancer patients is suppressed that is characterized by lower T cell counts, less effector immune cells infiltration, higher levels of exhausted effector cells and higher levels of immunosuppressive cytokines, such as transforming growth factor β (TGF-β). Recombinant human IL-7 (rhIL-7) is an ideal solution for the immune reconstitution of lymphopenia patients by promoting peripheral T cell expansion. Furthermore, it can antagonize the immunosuppressive network. In animal models, IL-7 has been proven to prolong the survival of tumor-bearing hosts. In this review, we will focus on the mechanism of action and applications of IL-7 in cancer immunotherapy and the potential restrictions for its usage. PMID:25955647

  7. 'Action potential-like' ST elevation following pseudo-Wellens' electrocardiogram.

    PubMed

    Oksuz, Fatih; Sensoy, Baris; Sen, Fatih; Celik, Ethem; Ozeke, Ozcan; Maden, Orhan

    2015-01-01

    Coronary artery vasospasm is an important cause of chest pain syndromes that can lead to myocardial infarction, ventricular arrhythmias, and sudden death. In 1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST-segment elevation on electrocardiography. Persistent angina is challenging, and repeated coronary angioplasty may be required in this syndrome. Calcium antagonists are extremely effective in treating and preventing coronary spasm, and may provide long-lasting relief for the patient. Whereas the Wellens' syndrome is characterized by symmetrically inverted T-waves with preserved R waves in the precordial leads suggestive of impending myocardial infarction due to a critical proximal left anterior descending stenosis, the pseudo-Wellens' syndrome caused by coronary artery spasm has also rarely been reported in literature. We present a pseudo-Wellens syndrome as a cause of vasospastic angina, and a diffuse ST segment elavation on electrocardiogram resembling the Greek letter lambda, called also 'action potential-like' ECG in a patient with vasospastic-type Printzmetal angina. PMID:26432739

  8. A Hybrid Classifier for Characterizing Motor Unit Action Potentials in Diagnosing Neuromuscular Disorders

    PubMed Central

    Kamali, T; Boostani, R; Parsaei, H

    2013-01-01

    Background: The time and frequency features of motor unit action potentials (MUAPs) extracted from electromyographic (EMG) signal provide discriminative information for diagnosis and treatment of neuromuscular disorders. However, the results of conventional automatic diagnosis methods using MUAP features is not convincing yet. Objective: The main goal in designing a MUAP characterization system is obtaining high classification accuracy to be used in clinical decision system. For this aim, in this study, a robust classifier is proposed to improve MUAP classification performance in estimating the class label (myopathic, neuropathic and normal) of a given MUAP. Method: The proposed scheme employs both time and time–frequency features of a MUAP along with an ensemble of support vector machines (SVMs) classifiers in hybrid serial/parallel architecture. Time domain features includes phase, turn, peak to peak amplitude, area, and duration of the MUAP. Time–frequency features are discrete wavelet transform coefficients of the MUAP. Results: Evaluation results of the developed system using EMG signals of 23 subjects (7 with myopathic, 8 with neuropathic and 8 with no diseases)  showed that the system estimated the class label of MUAPs extracted from these signals with average of accuracy of 91% which is at least 5% higher than the accuracy of two previously presented methods. Conclusion: Using different optimized subsets of features along with the presented hybrid classifier results in a classification accuracy that is encouraging to be used in clinical applications for MUAP characterization.  PMID:25505761

  9. Motor unit action potential conduction velocity estimated from surface electromyographic signals using image processing techniques.

    PubMed

    Soares, Fabiano Araujo; Carvalho, João Luiz Azevedo; Miosso, Cristiano Jacques; de Andrade, Marcelino Monteiro; da Rocha, Adson Ferreira

    2015-01-01

    In surface electromyography (surface EMG, or S-EMG), conduction velocity (CV) refers to the velocity at which the motor unit action potentials (MUAPs) propagate along the muscle fibers, during contractions. The CV is related to the type and diameter of the muscle fibers, ion concentration, pH, and firing rate of the motor units (MUs). The CV can be used in the evaluation of contractile properties of MUs, and of muscle fatigue. The most popular methods for CV estimation are those based on maximum likelihood estimation (MLE). This work proposes an algorithm for estimating CV from S-EMG signals, using digital image processing techniques. The proposed approach is demonstrated and evaluated, using both simulated and experimentally-acquired multichannel S-EMG signals. We show that the proposed algorithm is as precise and accurate as the MLE method in typical conditions of noise and CV. The proposed method is not susceptible to errors associated with MUAP propagation direction or inadequate initialization parameters, which are common with the MLE algorithm. Image processing -based approaches may be useful in S-EMG analysis to extract different physiological parameters from multichannel S-EMG signals. Other new methods based on image processing could also be developed to help solving other tasks in EMG analysis, such as estimation of the CV for individual MUs, localization and tracking of innervation zones, and study of MU recruitment strategies. PMID:26384112

  10. Adhesion to Carbon Nanotube Conductive Scaffolds Forces Action-Potential Appearance in Immature Rat Spinal Neurons

    PubMed Central

    Toma, Francesca Maria; Calura, Enrica; Rizzetto, Lisa; Carrieri, Claudia; Roncaglia, Paola; Martinelli, Valentina; Scaini, Denis; Masten, Lara; Turco, Antonio; Gustincich, Stefano; Prato, Maurizio; Ballerini, Laura

    2013-01-01

    In the last decade, carbon nanotube growth substrates have been used to investigate neurons and neuronal networks formation in vitro when guided by artificial nano-scaled cues. Besides, nanotube-based interfaces are being developed, such as prosthesis for monitoring brain activity. We recently described how carbon nanotube substrates alter the electrophysiological and synaptic responses of hippocampal neurons in culture. This observation highlighted the exceptional ability of this material in interfering with nerve tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote the development of immature neurons isolated from the neonatal rat spinal cord, and maintained in vitro. To address this issue we performed electrophysiological studies associated to gene expression analysis. Our results indicate that spinal neurons plated on electro-conductive carbon nanotubes show a facilitated development. Spinal neurons anticipate the expression of functional markers of maturation, such as the generation of voltage dependent currents or action potentials. These changes are accompanied by a selective modulation of gene expression, involving neuronal and non-neuronal components. Our microarray experiments suggest that carbon nanotube platforms trigger reparative activities involving microglia, in the absence of reactive gliosis. Hence, future tissue scaffolds blended with conductive nanotubes may be exploited to promote cell differentiation and reparative pathways in neural regeneration strategies. PMID:23951361

  11. Kv3.1 uses a timely resurgent K(+) current to secure action potential repolarization.

    PubMed

    Labro, Alain J; Priest, Michael F; Lacroix, Jérôme J; Snyders, Dirk J; Bezanilla, Francisco

    2015-01-01

    High-frequency action potential (AP) transmission is essential for rapid information processing in the central nervous system. Voltage-dependent Kv3 channels play an important role in this process thanks to their high activation threshold and fast closure kinetics, which reduce the neuron's refractory period. However, premature Kv3 channel closure leads to incomplete membrane repolarization, preventing sustainable AP propagation. Here, we demonstrate that Kv3.1b channels solve this problem by producing resurgent K(+) currents during repolarization, thus ensuring enough repolarizing power to terminate each AP. Unlike previously described resurgent Na(+) and K(+) currents, Kv3.1b's resurgent current does not originate from recovery of channel block or inactivation but results from a unique combination of steep voltage-dependent gating kinetics and ultra-fast voltage-sensor relaxation. These distinct properties are readily transferrable onto an orthologue Kv channel by transplanting the voltage-sensor's S3-S4 loop, providing molecular insights into the mechanism by which Kv3 channels contribute to high-frequency AP transmission. PMID:26673941

  12. Multifocal Fluorescence Microscope for Fast Optical Recordings of Neuronal Action Potentials

    PubMed Central

    Shtrahman, Matthew; Aharoni, Daniel B.; Hardy, Nicholas F.; Buonomano, Dean V.; Arisaka, Katsushi; Otis, Thomas S.

    2015-01-01

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera’s native frame rate. We demonstrate that this approach is capable of recording Ca2+ transients resulting from APs in neurons labeled with the Ca2+ sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. PMID:25650920

  13. Impact of calcium-activated potassium channels on NMDA spikes in cortical layer 5 pyramidal neurons.

    PubMed

    Bock, Tobias; Stuart, Greg J

    2016-03-01

    Active electrical events play an important role in shaping signal processing in dendrites. As these events are usually associated with an increase in intracellular calcium, they are likely to be under the control of calcium-activated potassium channels. Here, we investigate the impact of calcium-activated potassium channels onN-methyl-d-aspartate (NMDA) receptor-dependent spikes, or NMDA spikes, evoked by glutamate iontophoresis onto basal dendrites of cortical layer 5 pyramidal neurons. We found that small-conductance calcium-activated potassium channels (SK channels) act to reduce NMDA spike amplitude but at the same time, also decrease the iontophoretic current required for their generation. This SK-mediated decrease in NMDA spike threshold was dependent on R-type voltage-gated calcium channels and indicates a counterintuitive, excitatory effect of SK channels on NMDA spike generation, whereas the capacity of SK channels to suppress NMDA spike amplitude is in line with the expected inhibitory action of potassium channels on dendritic excitability. Large-conductance calcium-activated potassium channels had no significant impact on NMDA spikes, indicating that these channels are either absent from basal dendrites or not activated by NMDA spikes. These experiments reveal complex and opposing interactions among NMDA receptors, SK channels, and voltage-gated calcium channels in basal dendrites of cortical layer 5 pyramidal neurons during NMDA spike generation, which are likely to play an important role in regulating the way these neurons integrate the thousands of synaptic inputs they receive. PMID:26936985

  14. Spatio-temporal pattern recognizers using spiking neurons and spike-timing-dependent plasticity.

    PubMed

    Humble, James; Denham, Susan; Wennekers, Thomas

    2012-01-01

    It has previously been shown that by using spike-timing-dependent plasticity (STDP), neurons can adapt to the beginning of a repeating spatio-temporal firing pattern in their input. In the present work, we demonstrate that this mechanism can be extended to train recognizers for longer spatio-temporal input signals. Using a number of neurons that are mutually connected by plastic synapses and subject to a global winner-takes-all mechanism, chains of neurons can form where each neuron is selective to a different segment of a repeating input pattern, and the neurons are feed-forwardly connected in such a way that both the correct input segment and the firing of the previous neurons are required in order to activate the next neuron in the chain. This is akin to a simple class of finite state automata. We show that nearest-neighbor STDP (where only the pre-synaptic spike most recent to a post-synaptic one is considered) leads to "nearest-neighbor" chains where connections only form between subsequent states in a chain (similar to classic "synfire chains"). In contrast, "all-to-all spike-timing-dependent plasticity" (where all pre- and post-synaptic spike pairs matter) leads to multiple connections that can span several temporal stages in the chain; these connections respect the temporal order of the neurons. It is also demonstrated that previously learnt individual chains can be "stitched together" by repeatedly presenting them in a fixed order. This way longer sequence recognizers can be formed, and potentially also nested structures. Robustness of recognition with respect to speed variations in the input patterns is shown to depend on rise-times of post-synaptic potentials and the membrane noise. It is argued that the memory capacity of the model is high, but could theoretically be increased using sparse codes. PMID:23087641

  15. Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

    NASA Astrophysics Data System (ADS)

    Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

    2011-11-01

    The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

  16. Rapid Ca2+ flux through the transverse tubular membrane, activated by individual action potentials in mammalian skeletal muscle

    PubMed Central

    Launikonis, Bradley S; Stephenson, D George; Friedrich, Oliver

    2009-01-01

    Periods of low frequency stimulation are known to increase the net Ca2+ uptake in skeletal muscle but the mechanism responsible for this Ca2+ entry is not known. In this study a novel high-resolution fluorescence microscopy approach allowed the detection of an action potential-induced Ca2+ flux across the tubular (t-) system of rat extensor digitorum longus muscle fibres that appears to be responsible for the net uptake of Ca2+ in working muscle. Action potentials were triggered in the t-system of mechanically skinned fibres from rat by brief field stimulation and t-system [Ca2+] ([Ca2+]t-sys) and cytoplasmic [Ca2+] ([Ca2+]cyto) were simultaneously resolved on a confocal microscope. When initial [Ca2+]t-sys was ≥ 0.2 mm a Ca2+ flux from t-system to the cytoplasm was observed following a single action potential. The action potential-induced Ca2+ flux and associated t-system Ca2+ permeability decayed exponentially and displayed inactivation characteristics such that further Ca2+ entry across the t-system could not be observed after 2–3 action potentials at 10 Hz stimulation rate. When [Ca2+]t-sys was closer to 0.1 mm, a transient rise in [Ca2+]t-sys was observed almost concurrently with the increase in [Ca2+]cyto following the action potential. The change in direction of Ca2+ flux was consistent with changes in the direction of the driving force for Ca2+. This is the first demonstration of a rapid t-system Ca2+ flux associated with a single action potential in mammalian skeletal muscle. The properties of this channel are inconsistent with a flux through the L-type Ca2+ channel suggesting that an as yet unidentified t-system protein is conducting this current. This action potential-activated Ca2+ flux provides an explanation for the previously described Ca2+ entry and accumulation observed with prolonged, intermittent muscle activity. PMID:19332499

  17. Automatic Spike Sorting Using Tuning Information

    PubMed Central

    Ventura, Valérie

    2011-01-01

    Current spike sorting methods focus on clustering neurons’ characteristic spike waveforms. The resulting spike-sorted data are typically used to estimate how covariates of interest modulate the firing rates of neurons. However, when these covariates do modulate the firing rates, they provide information about spikes’ identities, which thus far have been ignored for the purpose of spike sorting. This letter describes a novel approach to spike sorting, which incorporates both waveform information and tuning information obtained from the modulation of firing rates. Because it efficiently uses all the available information, this spike sorter yields lower spike misclassification rates than traditional automatic spike sorters. This theoretical result is verified empirically on several examples. The proposed method does not require additional assumptions; only its implementation is different. It essentially consists of performing spike sorting and tuning estimation simultaneously rather than sequentially, as is currently done. We used an expectation-maximization maximum likelihood algorithm to implement the new spike sorter. We present the general form of this algorithm and provide a detailed implementable version under the assumptions that neurons are independent and spike according to Poisson processes. Finally, we uncover a systematic flaw of spike sorting based on waveform information only. PMID:19548802

  18. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    USGS Publications Warehouse

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  19. A Computational Study of Spike Time Reliability in Two Types of Threshold Dynamics

    PubMed Central

    2013-01-01

    Spike time reliability (STR) refers to the phenomenon in which repetitive applications of a frozen copy of one stochastic signal to a neuron trigger spikes with reliable timing while a constant signal fails to do so. Observed and explored in numerous experimental and theoretical studies, STR is a complex dynamic phenomenon depending on the nature of external inputs as well as intrinsic properties of a neuron. The neuron under consideration could be either quiescent or spontaneously spiking in the absence of the external stimulus. Focusing on the situation in which the unstimulated neuron is quiescent but close to a switching point to oscillations, we numerically analyze STR treating each spike occurrence as a time localized event in a model neuron. We study both the averaged properties as well as individual features of spike-evoking epochs (SEEs). The effects of interactions between spikes is minimized by selecting signals that generate spikes with relatively long interspike intervals (ISIs). Under these conditions, the frequency content of the input signal has little impact on STR. We study two distinct cases, Type I in which the f–I relation (f for frequency, I for applied current) is continuous and Type II where the f–I relation exhibits a jump. STR in the two types shows a number of similar features and differ in some others. SEEs that are capable of triggering spikes show great variety in amplitude and time profile. On average, reliable spike timing is associated with an accelerated increase in the “action” of the signal as a threshold for spike generation is approached. Here, “action” is defined as the average amount of current delivered during a fixed time interval. When individual SEEs are studied, however, their time profiles are found important for triggering more precisely timed spikes. The SEEs that have a more favorable time profile are capable of triggering spikes with higher precision even at lower action levels. PMID:23945258

  20. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    PubMed

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  1. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    ERIC Educational Resources Information Center

    de Vreede, Catherine; Warner, Alan; Pitter, Robert

    2014-01-01

    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

  2. Measuring multiple spike train synchrony.

    PubMed

    Kreuz, Thomas; Chicharro, Daniel; Andrzejak, Ralph G; Haas, Julie S; Abarbanel, Henry D I

    2009-10-15

    Measures of multiple spike train synchrony are essential in order to study issues such as spike timing reliability, network synchronization, and neuronal coding. These measures can broadly be divided in multivariate measures and averages over bivariate measures. One of the most recent bivariate approaches, the ISI-distance, employs the ratio of instantaneous interspike intervals (ISIs). In this study we propose two extensions of the ISI-distance, the straightforward averaged bivariate ISI-distance and the multivariate ISI-diversity based on the coefficient of variation. Like the original measure these extensions combine many properties desirable in applications to real data. In particular, they are parameter-free, time scale independent, and easy to visualize in a time-resolved manner, as we illustrate with in vitro recordings from a cortical neuron. Using a simulated network of Hindemarsh-Rose neurons as a controlled configuration we compare the performance of our methods in distinguishing different levels of multi-neuron spike train synchrony to the performance of six other previously published measures. We show and explain why the averaged bivariate measures perform better than the multivariate ones and why the multivariate ISI-diversity is the best performer among the multivariate methods. Finally, in a comparison against standard methods that rely on moving window estimates, we use single-unit monkey data to demonstrate the advantages of the instantaneous nature of our methods. PMID:19591867

  3. Contribution of apamin-sensitive SK channels to the firing precision but not to the slow afterhyperpolarization and spike frequency adaptation in snail neurons.

    PubMed

    Vatanparast, Jafar; Janahmadi, Mahyar

    2009-02-19

    Apamin-sensitive small conductance Ca(2+)-dependent K(+)(SK) channels are generally accepted as responsible for the medium afterhyperpolarization (mAHP) after single or train of action potentials. Here, we examined the functional involvement of these channels in the firing precision, post train AHP and spike frequency adaptation (SFA) in neurons of snail Caucasotachea atrolabiata. Apamin, a selective SK channel antagonist, reduced the duration of single-spike AHP and disrupted the spontaneous rhythmic activity. High frequency trains of evoked action potentials showed a time-dependent decrease in the action potential discharge rate (spike frequency adaptation) and followed by a prominent post stimulus inhibitory period (PSIP) as a marker of slow AHP (sAHP). Neither sAHP nor SFA was attenuated by apamin, suggesting that apamin-sensitive SK channels can strongly affect the rhythmicity, but are probably not involved in the SFA and sAHP. Nifedipine, antagonist of L-type Ca(2+) channels, decreased the firing frequency and neuronal rhythmicity. When PSIP was normalized to the background interspike interval, a suppressing effect of nifedipine on PSIP was also observed. Intracellular iontophoretic injection of BAPTA, a potent Ca(2+) chelator, dramatically suppressed PSIP that confirms the intracellular Ca(2+) dependence of the sAHP, but had no discernable effect on the SFA. During train-evoked activity a reduction in the action potential overshoot and maximum depolarization rate was also observed, along with a decrease in the firing frequency, while the action potential threshold increased, which indicated that Na(+) channels, rather than Ca(2+)-dependent K(+) channels, are involved in the SFA. PMID:19100724

  4. Reliable detection of predator cues in afferent spike trains of a katydid under high background noise levels

    PubMed Central

    Hartbauer, Manfred; Radspieler, Gerald; Römer, Heiner

    2014-01-01

    SUMMARY Katydid receivers face the problem of detecting behaviourally relevant predatory cues from echolocating bats in the same frequency domain as their own conspecific mating signals. We therefore tested the hypothesis that katydids are able to detect the presence of insectivorous bats in spike discharges at early stages of nervous processing in the auditory pathway by using the temporal details characteristic for responses to echolocation sequences. Spike activity was recorded from an identified nerve cell (omega neuron) under both laboratory and field conditions. In the laboratory, the preparation was stimulated with sequences of bat calls at different repetition rates typical for the guild of insectivorous bats, in the presence of background noise. The omega cell fired brief high-frequency bursts of action potentials in response to each bat sound pulse. Repetition rates of 18 and 24 Hz of these pulses resulted in a suppression of activity resulting from background noise, thus facilitating the detection of bat calls. The spike activity typical for responses to bat echolocation contrasts to responses to background noise, producing different distributions of inter-spike intervals. This allowed development of a ‘neuronal bat detector’ algorithm, optimized to detect responses to bats in afferent spike trains. The algorithm was applied to more than 24 hours of outdoor omega-recordings performed either at a rainforest clearing with high bat activity or in rainforest understory, where bat activity was low. In 95% of cases, the algorithm detected a bat reliably, even under high background noise, and correctly rejected responses when an electronic bat detector showed no response. PMID:20709932

  5. Reliable detection of predator cues in afferent spike trains of a katydid under high background noise levels.

    PubMed

    Hartbauer, Manfred; Radspieler, Gerald; Römer, Heiner

    2010-09-01

    Katydid receivers face the problem of detecting behaviourally relevant predatory cues from echolocating bats in the same frequency domain as their own conspecific mating signals. We therefore tested the hypothesis that katydids are able to detect the presence of insectivorous bats in spike discharges at early stages of nervous processing in the auditory pathway by using the temporal details characteristic for responses to echolocation sequences. Spike activity was recorded from an identified nerve cell (omega neuron) under both laboratory and field conditions. In the laboratory, the preparation was stimulated with sequences of bat calls at different repetition rates typical for the guild of insectivorous bats, in the presence of background noise. The omega cell fired brief high-frequency bursts of action potentials in response to each bat sound pulse. Repetition rates of 18 and 24 Hz of these pulses resulted in a suppression of activity resulting from background noise, thus facilitating the detection of bat calls. The spike activity typical for responses to bat echolocation contrasts to responses to background noise, producing different distributions of inter-spike intervals. This allowed development of a 'neuronal bat detector' algorithm, optimized to detect responses to bats in afferent spike trains. The algorithm was applied to more than 24 hours of outdoor omega-recordings performed either at a rainforest clearing with high bat activity or in rainforest understory, where bat activity was low. In 95% of cases, the algorithm detected a bat reliably, even under high background noise, and correctly rejected responses when an electronic bat detector showed no response. PMID:20709932

  6. Learning real-world stimuli in a neural network with spike-driven synaptic dynamics.

    PubMed

    Brader, Joseph M; Senn, Walter; Fusi, Stefano

    2007-11-01

    We present a model of spike-driven synaptic plasticity inspired by experimental observations and motivated by the desire to build an electronic hardware device that can learn to classify complex stimuli in a semisupervised fashion. During training, patterns of activity are sequentially imposed on the input neurons, and an additional instructor signal drives the output neurons toward the desired activity. The network is made of integrate-and-fire neurons with constant leak and a floor. The synapses are bistable, and they are modified by the arrival of presynaptic spikes. The sign of the change is determined by both the depolarization and the state of a variable that integrates the postsynaptic action potentials. Following the training phase, the instructor signal is removed, and the output neurons are driven purely by the activity of the input neurons weighted by the plastic synapses. In the absence of stimulation, the synapses preserve their internal state indefinitely. Memories are also very robust to the disruptive action of spontaneous activity. A network of 2000 input neurons is shown to be able to classify correctly a large number (thousands) of highly overlapping patterns (300 classes of preprocessed Latex characters, 30 patterns per class, and a subset of the NIST characters data set) and to generalize with performances that are better than or comparable to those of artificial neural networks. Finally we show that the synaptic dynamics is compatible with many of the experimental observations on the induction of long-term modifications (spike-timing-dependent plasticity and its dependence on both the postsynaptic depolarization and the frequency of pre- and postsynaptic neurons). PMID:17883345

  7. iSpike: a spiking neural interface for the iCub robot.

    PubMed

    Gamez, D; Fidjeland, A K; Lazdins, E

    2012-06-01

    This paper presents iSpike: a C++ library that interfaces between spiking neural network simulators and the iCub humanoid robot. It uses a biologically inspired approach to convert the robot's sensory information into spikes that are passed to the neural network simulator, and it decodes output spikes from the network into motor signals that are sent to control the robot. Applications of iSpike range from embodied models of the brain to the development of intelligent robots using biologically inspired spiking neural networks. iSpike is an open source library that is available for free download under the terms of the GPL. PMID:22617339

  8. Bacteriocins: modes of action and potentials in food preservation and control of food poisoning.

    PubMed

    Abee, T; Krockel, L; Hill, C

    1995-12-01

    Lactic acid bacteria (LAB) play an essential role in the majority of food fermentations, and a wide variety of strains are routinely employed as starter cultures in the manufacture of dairy, meat, vegetable and bakery products. One of the most important contributions of these microorganisms is the extended shelf life of the fermented product by comparison to that of the raw substrate. Growth of spoilage and pathogenic bacteria in these foods is inhibited due to competition for nutrients and the presence of starter-derived inhibitors such as lactic acid, hydrogen peroxide and bacteriocins (Ray and Daeschel, 1992). Bacteriocins, are a heterogenous group of anti-bacterial proteins that vary in spectrum of activity, mode of action, molecular weight, genetic origin and biochemical properties. Currently, artificial chemical preservatives are employed to limit the number of microorganisms capable of growing within foods, but increasing consumer awareness of potential health risks associated with some of these substances has led researchers to examine the possibility of using bacteriocins produced by LAB as biopreservatives. The major classes of bacteriocins produced by LAB include: (I) lantibiotics, (II) small heat stable peptides, (III) large heat labile proteins, and (IV) complex proteins whose activity requires the association of carbohydrate or lipid moieties (Klaenhammer, 1993). Significantly however, the inhibitory activity of these substances is confined to Gram-positive bacteria and inhibition of Gram-negatives by these bacteriocins has not been demonstrated, an observation which can be explained by a detailed analysis and comparison of the composition of Gram-positive and Gram-negative bacterial cell walls (Fig. 1). In both types the cytoplasmic membrane which forms the border between the cytoplasm and the external environment, is surrounded by a layer of peptidoglycan which is significantly thinner in Gram-negative bacteria than in Gram-positive bacteria. Gram

  9. Electrical spiking in bacterial biofilms

    PubMed Central

    Masi, Elisa; Ciszak, Marzena; Santopolo, Luisa; Frascella, Arcangela; Giovannetti, Luciana; Marchi, Emmanuela; Viti, Carlo; Mancuso, Stefano

    2015-01-01

    In nature, biofilms are the most common form of bacterial growth. In biofilms, bacteria display coordinated behaviour to perform specific functions. Here, we investigated electrical signalling as a possible driver in biofilm sociobiology. Using a multi-electrode array system that enables high spatio-temporal resolution, we studied the electrical activity in two biofilm-forming strains and one non-biofilm-forming strain. The action potential rates monitored during biofilm-forming bacterial growth exhibited a one-peak maximum with a long tail, corresponding to the highest biofilm development. This peak was not observed for the non-biofilm-forming strain, demonstrating that the intensity of the electrical activity was not linearly related to the bacterial density, but was instead correlated with biofilm formation. Results obtained indicate that the analysis of the spatio-temporal electrical activity of bacteria during biofilm formation can open a new frontier in the study of the emergence of collective microbial behaviour. PMID:25392401

  10. Effect of temperature on isoprenaline- and barium-induced slow action potentials in guinea-pig ventricular strips.

    PubMed

    Manzini, S; Parlani, M; Martucci, E; Maggi, C A; Meli, A

    1986-01-01

    The effect of variation in temperature (37-32 and 27 degrees C) on electrical and mechanical activity of depolarized and isoprenaline- or barium-reactivated guinea pig ventricular strips was studied. Lowering the temperature brings a marked prolongation of isoprenaline-induced slow action potentials. In addition the maximal rate of depolarization was strongly reduced at lower temperatures. These effects were observed at an extracellular Ca2+ concentration of either 0.9 or 2.5 mM. The accompanying mechanical activities was significantly increased by reduction in temperature. Barium-induced slow action potentials were similarly affected by temperature variations. These observations suggest that hypothermia exert a sort of calcium antagonistic action probably coupled to a reduction of repolarizing outward potassium currents. PMID:2430855

  11. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.

    PubMed

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C

    2016-08-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377724

  12. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons

    PubMed Central

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C.

    2016-01-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca2+ entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca2+ buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca2+-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca2+ elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377724

  13. Halothane diminishes changes in cardiac fiber action potential duration induced by hypocarbia and hypercarbia.

    PubMed

    Stowe, D F; Bosnjak, Z J; Kampine, J P

    1984-09-01

    Both halothane (HAL) and acid-base changes produce cardiac arrhythmias in humans. The authors' aim was to determine if HAL alters the effects of hypercapnic acidosis and hypocapnic alkalosis on action potential (AP) properties of ventricular muscle fibers. They superfused the paced right ventricle of 15 guinea pig hearts with non-HCO3- buffered salt solution and recorded transmembrane APs with 3 M KCl microelectrodes in 35 subendocardial cells. Random changes in the fractions of HAL were made during low (12% CO2 in O2), normal (5% CO2 in O2), and high (0% CO2 in O2) pH. Compared with controls at pH 7.44, AP duration (APD) and effective refractory period (ERP) significantly decreased by 7 and 4% at pH 8.08 and increased by 7 and 9% at pH 7.09. At pH 7.44, 0.7-2.1% HAL produced no change in APD; but 2.1% increased ERP, while 3.5% HAL decreased ERP. At pH 8.08, the decrease in ERP induced with alkalosis alone was converted to an increase with 1.4 and 2.1% HAL. At pH 7.09, 0.7-1.4% HAL had no additional effect on the acidosis-induced increases in APD and ERP, but 2.1 and 2.8% HAL greatly reduced these responses. At HAL fractions greater than 1.4% the marked inverse changes in APD and ERP, induced alone by acidosis and alkalosis, were no longer significantly different from control. This study shows that the opposing effects of alkalosis to shorten and of acidosis to lengthen APD and ERP were attenuated at low levels and abolished at high levels of HAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6433748

  14. Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.

    PubMed

    Chang, C L T; Chen, Yi-Ching; Chen, Hui-Ming; Yang, Ning-Sun; Yang, Wen-Chin

    2013-01-01

    Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic β-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic β-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed. PMID:23210779

  15. A potential role for cannabinoid receptors in the therapeutic action of fenofibrate.

    PubMed

    Priestley, Richard S; Nickolls, Sarah A; Alexander, Stephen P H; Kendall, David A

    2015-04-01

    Cannabinoids are reported to have actions through peroxisome proliferator-activated receptors (PPARs), which led us to investigate PPAR agonists for activity at the cannabinoid receptors. Radio-ligand binding and functional assays were conducted using human recombinant cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors, as well as the guinea pig isolated ileum, using the full agonist CP55940 as a positive control. The PPAR-α agonist fenofibrate exhibited submicromolar affinity for both receptors (pKi CB1, 6.3 ± 0.1; CB2, 7.7 ± 0.1). Functionally, fenofibrate acted as an agonist at the CB2 receptor (pEC50, 7.7 ± 0.1) and a partial agonist at the CB1 receptor, although with a decrease in functional response at higher concentrations, producing bell-shaped concentration-response curves. High concentrations of fenofibrate were able to increase the dissociation rate constant for [(3)H]-CP55940 at the CB1 receptor, (kfast without: 1.2 ± 0.2/min; with: 3.8 ± 0.1 × 10(-2)/min) and decrease the maximal response to CP55940 (Rmax, 86 ± 2%), which is consistent with a negative allosteric modulator. Fenofibrate also reduced electrically induced contractions in isolated guinea pig ileum via CB1 receptors (pEC50, 6.0 ± 0.4). Fenofibrate is thus identified as an example of a new class of cannabinoid receptor ligand and allosteric modulator, with the potential to interact therapeutically with cannabinoid receptors in addition to its primary PPAR target. PMID:25550466

  16. Disruption of action potential and calcium signaling properties in malformed myofibers from dystrophin-deficient mice

    PubMed Central

    Hernández-Ochoa, Erick O; Pratt, Stephen J P; Garcia-Pelagio, Karla P; Schneider, Martin F; Lovering, Richard M

    2015-01-01

    Duchenne muscular dystrophy (DMD), the most common and severe muscular dystrophy, is caused by the absence of dystrophin. Muscle weakness and fragility (i.e., increased susceptibility to damage) are presumably due to structural instability of the myofiber cytoskeleton, but recent studies suggest that the increased presence of malformed/branched myofibers in dystrophic muscle may also play a role. We have previously studied myofiber morphology in healthy wild-type (WT) and dystrophic (MDX) skeletal muscle. Here, we examined myofiber excitability using high-speed confocal microscopy and the voltage-sensitive indicator di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS) to assess the action potential (AP) properties. We also examined AP-induced Ca2+ transients using high-speed confocal microscopy with rhod-2, and assessed sarcolemma fragility using elastimetry. AP recordings showed an increased width and time to peak in malformed MDX myofibers compared to normal myofibers from both WT and MDX, but no significant change in AP amplitude. Malformed MDX myofibers also exhibited reduced AP-induced Ca2+ transients, with a further Ca2+ transient reduction in the branches of malformed MDX myofibers. Mechanical studies indicated an increased sarcolemma deformability and instability in malformed MDX myofibers. The data suggest that malformed myofibers are functionally different from myofibers with normal morphology. The differences seen in AP properties and Ca2+ signals suggest changes in excitability and remodeling of the global Ca2+ signal, both of which could underlie reported weakness in dystrophic muscle. The biomechanical changes in the sarcolemma support the notion that malformed myofibers are more susceptible to damage. The high prevalence of malformed myofibers in dystrophic muscle may contribute to the progressive strength loss and fragility seen in dystrophic muscles. PMID:25907787

  17. Inter-Subject Variability in Human Atrial Action Potential in Sinus Rhythm versus Chronic Atrial Fibrillation

    PubMed Central

    Sánchez, Carlos; Bueno-Orovio, Alfonso; Wettwer, Erich; Loose, Simone; Simon, Jana; Ravens, Ursula; Pueyo, Esther; Rodriguez, Blanca

    2014-01-01

    Aims Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR) and chronic atrial fibrillation (cAF) patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP) recorded in 363 patients both under SR and cAF conditions. Methods and Results Human AP recordings in atrial trabeculae (n = 469) from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in GK1, GKur and Gto, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in IK1 and INaK underlies variability in APD90, variability in IKur, ICaL and INaK modulates variability in APD50 and combined variability in Ito and IKur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by IK1 and either INaK or INaCa depending on the model. Conclusion Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in

  18. Mathematical simulations of ligand-gated and cell-type specific effects on the action potential of human atrium

    PubMed Central

    Maleckar, Mary M.; Greenstein, Joseph L.; Trayanova, Natalia A.; Giles, Wayne R.

    2010-01-01

    In the mammalian heart, myocytes and fibroblasts can communicate via gap junction, or connexin-mediated current flow. Some of the effects of this electrotonic coupling on the action potential waveform of the human ventricular myocyte have been analyzed in detail. The present study employs a recently developed mathematical model of the human atrial myocyte to investigate the consequences of this heterogeneous cell–cell interaction on the action potential of the human atrium. Two independent physiological processes which alter the physiology of the human atrium have been studied. i) The effects of the autonomic transmitter acetylcholine on the atrial action potential have been investigated by inclusion of a time-independent, acetylcholine-activated K+ current in this mathematical model of the atrial myocyte. ii) A non-selective cation current which is activated by natriuretic peptides has been incorporated into a previously published mathematical model of the cardiac fibroblast. These results identify subtle effects of acetylcholine, which arise from the nonlinear interactions between ionic currents in the human atrial myocyte. They also illustrate marked alterations in the action potential waveform arising from fibroblast–myocyte source–sink principles when the natriuretic peptide-mediated cation conductance is activated. Additional calculations also illustrate the effects of simultaneous activation of both of these cell-type specific conductances within the atrial myocardium. This study provides a basis for beginning to assess the utility of mathematical modeling in understanding detailed cell–cell interactions within the complex paracrine environment of the human atrial myocardium. PMID:19186188

  19. The effect of stimulation frequency on the transmural ventricular monophasic action potential in yellowfin tuna Thunnus albacares.

    PubMed

    Patrick, S M; White, E; Brill, R W; Shiels, H A

    2011-02-01

    Monophasic action potentials (MAPs) were recorded from the spongy and compact layers of the yellowfin tuna Thunnus albacares ventricle as stimulation frequency was increased. MAP duration decreased with increase in stimulation frequency in both the spongy and compact myocardial layers, but no significant difference in MAP duration was observed between the layers. PMID:21284642

  20. Assessing the global meltwater spike*1

    NASA Astrophysics Da