Single Electrical Pulse Research Articles

Effects of epidural spinal cord electrical stimulation with varying voltage and frequency on spinal cord refle-xes

Objective To investigate the effects of epidural spinal cord electrical stimulation (ESCES) on spinal cord reflexes in normal adult rats, and to find out where and how the spinal cord reflexes are generated. Methods Ten adult female Sprague Dawley rats were anaesthetized and an electrode was placed at the S, spinal cord segment. Single electric pulses with 200 μs pulse width and voltages of 400 mV, 600 mV and 1200 mV were used in the ESCES. 1200 mV voltages with 50 Hz, 60 Hz, 80 Hz, 100 Hz frequency were also tested. EMG signals were re-corded with concentric needle electrodes in the rats' semitendinosus muscles to observe the characteristics of spinal cord reflexes. Results The voltage threshold for generating semitendinosus muscle response was 300 mV. The three ESCES voltages induced 2 kinds of spinal cord reflexes. The 400 mV and 600 mV stimulation induced spinal cord reflexes with short latency (5.27±0.36 ms and 5.19±0.67 ms respectively). The 1200 mV stimulation volt-age induced spinal cord reflexes with long latency (2.57±0.23 ms). Spinal cord reflexes could be generated by 50 Hz, 60 Hz, 80 Hz, and 100 Hz ESCES. At the higher frequencies, spinal cord reflexes declined late in the ex-periments and then appeared irregular. In some of the rats, spinal cord reflexes vanished entirely late in the stimula-tion experiments. The latency and duration of the spinal cord reflexes induced by 50 Hz ESCES were (4.46 ± 1.07) ms and (7.33±1.00)ms respectively. These were significantly different from the latency and duration initia-ted by 60 Hz, 80 Hz or 100 Hz ESCES. Conclusions Different ESCES voltages induce different spinal cord refle-xes generated differently. The long latency reflexes might be monosynaptic responses mediated by dorsal root excite-ment, while the short latency reflexes might be sarcous exciting electric activity mediated by direct excitement of mo-tor neurons or motor fibers. The irregular spinal cord reflexes induced by higher frequency ESCES might be one kind of monosynaptic response. Irregularly appearing spinal cord reflexes induced by higher frequency stimulation might due to the inhibitory effect of higher frequency stimulation. Key words: Epidural spinal cord electrical stimulation; Voltage ; Frequency; Spinal cord ; Spinalcord reflexes

Electrical Conductivity of Thin Polycrystalline La0.83Sr0.17MnO3 Films in Pulsed High Electric and Magnetic Fields

The electrical conductivity of thin polycrystalline La0.83Sr0.17MnO3 films was investigated. These films were simultaneously affected by a single electrical pulse having a pulse length of several ns and a half-sinus magnetic pulse with a pulse length of 1 ms and amplitude ranging up to 20 T. The influence of the high magnetic field on the electroresistance was studied at electric field strengths up to 80 kV/cm when the temperature of the film ranged from 100 K to 300 K. It was found that depending on the temperature and magnetic field value the electroresistance (ER) can be enhanced or suppressed by the applied magnetic field. These results are explained by assuming that the ER appears due to inelastic multistep tunneling through grain boundaries and by taking into account the redistribution of voltage across crystalline grains and grain boundary regions.

52 ESTABLISHMENT OF A PREGNANCY WITH IDENTICAL TWINS AFTER THE TRANSFER OF A VITRIFIED CLONED BOVINE EMBRYO

Identical twin pregnancies occur naturally in some species because of spontaneous embryo division during initial stages in development. Bovine embryo splitting usually does not compromise subsequent in vivo development, being a method commonly used in embryo transfer programs to enhance overall pregnancy and parity rates. The goal of this study was to establish pregnancies from vitrified bovine cloned embryos. A spontaneous twin pregnancy was obtained after the transfer of a vitrified cloned hatching blastocyst produced by nuclear transfer procedures. Briefly, selected COCs obtained via slicing from bovine ovaries collected in a local slaughterhouse, and in vitro-matured for 17 h, were denuded by pipetting in HEPES-SOF (HSOF)-BSA and screened for the presence of the first polar body. Selected oocytes were enucleated by micromanipulation in HSOF + cytochalasin B and Hoechst 33 342 under UV fluorescence control. Frozen-thawed cumulus cells obtained by ovum pickup (OPU) from a Holstein cow were used as nucleus donors at passage 2 and high confluence (>90%). A single cell was inserted into the perivitelline space by micromanipulation. Fusion was induced electrically between two 200-μm-wide electrodes, 150 μm apart, using a single 20-V electrical DC pulse for 45 μs. Fusion outcome was observed 30 min after the electrical stimulus, with the immediate activation of the reconstructed embryos in ionomycin for 5 min, followed by incubation in cycloheximide and cytochalasin D for 5 h. Then, activated embryos were cultured in vitro for 7 days in SOF with amino acids (SOFaa) +10% estrous cow serum (ECS), at 39°C, high humidity, and 5% CO2, 5% O2 and 90% N2. Day-7 blastocysts were vitrified in hand-pulled glass micropipettes (GMP) using super-cooled LN2 (Vieira et al. 2007 Anim. Reprod. Sci. 99, 377-383), with the subsequent transfer of the GMP content into a straw upon warming, for the direct transfer of 4 embryos to female recipients, 1 per recipient, without the embryo evaluation under a stereomicroscope (Vieira et al. 2008 Reprod. Domest. Anim. 43, 314-318). A pregnancy was diagnosed on Day 35; on Day 260 of pregnancy, the female recipient aborted identical 20-kg twin fetuses showing no macro- or microscopic alterations following the necropsy. Samples of donor cells and tissue samples from the female recipient and cloned twins subjected to microsatellite DNA analysis confirmed that the twins were indeed identical clones and derived from the donor cells. The embryo from which the twin pregnancy derived was a hatching blastocyst, vitrified when about half of the embryo, including half of the inner cell mass, was projected outside the zona pellucida. Most likely, the hatching blastocyst was physically and unintentionally bisected during the process of vitrification, warming, or embryo transfer, producing hemi-embryos that later developed into identical twins. This work was supported by the Brazilian National Council for Scientific and Technological Development (CNPq).

Nanostructure formation in the surface layer of metals under influence of high-power electric current pulse

The possibility to tailor the microstructure of metals is explored utilising a skin-effect for surface treatment. The theoretical simulation of the electric and magnetic fields in a metallic cylinder shows that melting followed by rapid quenching can occur in a skin layer of 5–10-μm thickness if the amplitude of a single electric pulse of several nanoseconds duration is of the order of hundreds kiloamperes. The experiments using the SUS304 stainless steel show that besides a thin amorphous layer, a specific nano-twin structure can form at the near-surface region. The appearance of nano-twins is explained considering the stress components arising at the surface layer and in the bulk of the specimen during shock wave propagation caused by temperature gradients and the Lorentz force. It is shown that the high stress amplitudes can arise locally, furnishing the required conditions for twin nucleation and resulting in intensive plastic deformation of the sub-surface layer.

Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function

BackgroundNeurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc).ResultsDA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D2 autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D2 autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D2 receptor antagonist, sulpiride (5 μM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D2 autoreceptors. In addition, initial blockade of D2 autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13).ConclusionTaken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D2 autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.

Studying diffusion in multilayer thin-film structures on silicon by the contact melting technique

Features of the contact melting in thin-film structures comprising an aluminum layer with a thickness of h1 = 5 μm and a metal (Ti, Ni, Mo) or semiconductor (Si, Ge) sublayer (h2 = 0.1 μm) on a single crystal silicon plate (h3 = 500 μm) have been studied. The contact melting was caused by single rectangular electric pulses with a current density of j < 9 × 1010 A/m2 and a duration of τ = 100–1000 μs passing through the Al layer. The duration and rate of melting in the samples were determined using voltage waveforms measured by an oscillograph. A method has been developed based on an analysis of the mechanisms of contact interaction in the Al film—sublayer system (with allowance for experimental data on the time of sublayer dissolution in the Al film) for estimating the coefficients of mutiphase diffusion of the system components during the passage of a current pulse.

Activity-dependent depression of medial prefrontal cortex inputs to accumbens neurons by the basolateral amygdala

The encoding of reward-predictive stimuli by neurons in the nucleus accumbens (NAcc) depends on integrated synaptic activity from the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) afferent inputs. In a previous study, we found that single electrical stimulation pulses applied to the BLA facilitate mPFC-evoked spiking in NAcc neurons in a timing-dependent manner, presumably by a fast glutamatergic mechanism. In the present study, the ability of repetitive BLA activation to modulate synaptic inputs to NAcc neurons through dopamine- or N-methyl-d-aspartate (NMDA)-dependent mechanisms is characterized. NAcc neurons receiving excitatory input from both mPFC and BLA were recorded in urethane-anesthetized rats. Train stimulation of the BLA depressed mPFC-evoked spiking in these neurons. This was not attributable to mechanisms involving NMDA or dopamine D1, D2, D3 or D5 receptors, since blockade of these receptors did not affect the BLA-mediated depression. BLA-mediated depression was only evident when the BLA stimulation evoked spikes in the recorded neuron; thus, depolarization of the recorded neuron may be critical for this effect. The ability of the BLA to suppress mPFC-to-NAcc signaling may be a mechanism by which normal or pathologically heightened emotional states disrupt goal-directed behavior in favor of emotionally-driven responses.

Adenosine A2A Receptor Modulation of Hippocampal CA3-CA1 Synapse Plasticity During Associative Learning in Behaving Mice

Previous in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation (LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A(2A) receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A(2A) receptor antagonist, SCH58261, upon a well-known associative learning paradigm-classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus (US). A single electrical pulse was presented to the Schaffer collateral-commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS-US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.) -injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261-injected mice. In conclusion, the endogenous activation of adenosine A(2A) receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.

Use of the Rotation Vector in Brownian Dynamics Simulation of Transient Electro‐Optical Properties

AbstractWe have recently developed a new singularity‐free algorithm for Brownian dynamics simulation of free rotational diffusion. The algorithm is rigorously derived from kinetic theory and makes use of the Cartesian components of the rotation vector as the generalized coordinates describing angular orientation. Here, we report on the application of this new algorithm in Brownian dynamics simulations of transient electro‐optical properties. This work serves two main purposes. Firstly, it demonstrates the integrity of the new algorithm for BD‐simulations of the most common transient electro‐optic experiments. Secondly, it provides new insight into the performance of the new algorithm compared to algorithms that make use of the Euler angles. We study the transient electrically induced birefringence in dilute solutions of rigid particles with anisotropic polarization tensor in response to external electric field pulses. The use of both one single electric pulse and two electric pulses with opposite polarity are being analyzed. We document that the new singularity‐free algorithm performs flawlessly. We find that, for these types of systems, the new singularity‐free algorithm, in general, outperforms similar algorithms based on the Euler angles. In a wider perspective, the most important aspect of this work is that it serves as an important reference for future development of efficient BD‐algorithms for studies of more complex systems. These systems include polymers consisting of rigid segments with single‐segment translational–rotational coupling, segment–segment fluid‐dynamic interactions and holonomic constraints.magnified image

Cellular contribution to vestibular signal processing - a modeling approach

Event Abstract Back to Event Cellular contribution to vestibular signal processing - a modeling approach Christian Rossert1, 2*, Hans Straka3 and Stefan Glasauer1 1 Bernstein Center for Computational Neuroscience, Germany 2 Ludwig-Maximilians-Universitaet, Institute for Clinical Neurosciences, Germany 3 Universite Paris Descartes, Laboratoire de Neurobiologie des Réseaux Sensorimoteurs, Centre National de la Recherche Scientifique, France Computational modeling of the vestibulo-ocular circuitry is essential for understanding the sensory-motor transformation that generates spatially and dynamically appropriate compensatory eye movements during self-motion. Central vestibular neurons in the brainstem are responsible for the major computational step that transforms head acceleration-related sensory vestibular signals into extraocular motor commands that cause compensatory eye motion for gaze stabilization. In frog, second-order vestibular neurons (2°VN) separate into two functional subgroups (tonic - phasic neurons) that distinctly differ in their intrinsic membrane properties and discharge characteristics. While tonic 2°VN exhibit a continuous discharge in response to positive current steps, phasic 2°VN display a brief, high-frequency burst of spikes but no continuous discharge, corresponding to class 1 and class 3 excitability, respectively. Based on the dynamics of sinusoidally modulated changes of the membrane potential, tonic 2°VN show low-pass filter-like response properties, whereas phasic 2°VN have band-pass filter-like characteristics. Correlated with these cellular properties, tonic and phasic 2°VN exhibit pronounced differences in subthreshold response dynamics and discharge kinetics during synaptic activation of individual labyrinthine nerve branches with sinusoidally modulated trains of single electrical pulses. Physio-pharmacological analyses indicated that the two types of 2°VN are differentially embedded into local inhibitory circuits that reinforce the cellular properties of these neurons, respectively, thus indicating a co-adaptation of intrinsic membrane and emerging network properties in the two neuronal subtypes. The channel mechanisms responsible for the different discharge characteristics of the two neuronal subtypes were revealed by a frequency-domain analysis in the subthreshold domain: tonic 2°VN exhibit an increasing impedance with membrane depolarization which likely results from an activation of persistent sodium currents, while phasic 2°VN show a decreasing impedance and increasing resonance with membrane depolarization due to the activation of low-threshold, voltage-dependent ID-type potassium channels. These results also revealed the necessary channel mechanisms to generate spiking multi-compartment models. By extending these models with conductance-based synapses that simulate the corresponding activation and inhibition it was possible to reproduce the distinct firing behavior of the two neuronal subtypes during intracellular and synaptic activation, respectively. By modifying different components of the intrinsic cellular or the synaptic circuit properties it is now possible to determine the relative contributions of membrane and network properties for vestibular signal processing. Selective modifications of different neuronal circuit components or particular properties of ion channel conductances in the model allow making predictions of how eco-physiological or patho-physiological changes affect vestibular signal processing and how cellular and network mechanisms might compensate for induced alterations. Acknowledgements:Supported by Bayerische Forschungsstiftung (C.R.) and Bundesministerium für Bildung und Forschung (BCCN 01GQ0440). Conference: Bernstein Conference on Computational Neuroscience, Frankfurt am Main, Germany, 30 Sep - 2 Oct, 2009. Presentation Type: Poster Presentation Topic: Sensory processing Citation: Rossert C, Straka H and Glasauer S (2009). Cellular contribution to vestibular signal processing - a modeling approach. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference on Computational Neuroscience. doi: 10.3389/conf.neuro.10.2009.14.157 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Aug 2009; Published Online: 28 Aug 2009. * Correspondence: Christian Rossert, Bernstein Center for Computational Neuroscience, Munich, Germany, christian.a@roessert.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Christian Rossert Hans Straka Stefan Glasauer Google Christian Rossert Hans Straka Stefan Glasauer Google Scholar Christian Rossert Hans Straka Stefan Glasauer PubMed Christian Rossert Hans Straka Stefan Glasauer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Electroporation microarray for parallel transfer of small interfering RNA into mammalian cells

This paper describes the fabrication of microarrays that enable the parallel electroporation of small interfering RNAs (siRNAs) into mammalian cells. To optimize the conditions of microarray preparation and electric pulsing, a self-assembled monolayer was formed on a gold electrode, and a cationic polymer was adsorbed by the entire surface of the monolayer. siRNA was then adsorbed by the cationically modified electrode through electrostatic interactions. Human embryonic kidney cells stably transformed with the expression construct of green fluorescent protein (GFP) were used to examine the electric pulse-triggered transfer of GFP-specific siRNA. A single electric pulse was applied to the cells cultured on the electrode at a field strength of 240 V cm(-1). The expression of GFP was significantly suppressed in a sequence-specific manner two days after pulsing. Microscopic observation and flow-cytometric analysis revealed that the expression of GFP was attenuated in the majority of cells in a loading-dependent manner. Moreover, the effect of siRNA could be temporally controlled by changing the culture periods before pulsing. When a micropatterned self-assembled monolayer was used as a platform for loading siRNA in an array format, gene silencing was spatially restricted to the regions where specific siRNA was loaded. From these results, we conclude that array-based electroporation provides an excellent means of individual transfer of siRNAs into mammalian cells for high-throughput gene function studies.

Differential Dynamic Processing of Afferent Signals in Frog Tonic and Phasic Second-Order Vestibular Neurons

The sensory-motor transformation of the large dynamic spectrum of head-motion-related signals occurs in separate vestibulo-ocular pathways. Synaptic responses of tonic and phasic second-order vestibular neurons were recorded in isolated frog brains after stimulation of individual labyrinthine nerve branches with trains of single electrical pulses. The timing of the single pulses was adapted from spike discharge patterns of frog semicircular canal nerve afferents during sinusoidal head rotation. Because each electrical pulse evoked a single spike in afferent fibers, the resulting sequences with sinusoidally modulated intervals and peak frequencies up to 100 Hz allowed studying the processing of presynaptic afferent inputs with in vivo characteristics in second-order vestibular neurons recorded in vitro in an isolated whole brain. Variation of pulse-train parameters showed that the postsynaptic compound response dynamics differ in the two types of frog vestibular neurons. In tonic neurons, subthreshold compound responses and evoked discharge patterns exhibited relatively linear dynamics and were generally aligned with pulse frequency modulation. In contrast, compound responses of phasic neurons were asymmetric with large leads of subthreshold response peaks and evoked spike discharge relative to stimulus waveform. These nonlinearities were caused by the particular intrinsic properties of phasic vestibular neurons and were facilitated by GABAergic and glycinergic inhibitory inputs from tonic type vestibular interneurons and by cerebellar circuits. Coadapted intrinsic filter and emerging network properties thus form dynamically different neuronal elements that provide the appropriate cellular basis for a parallel processing of linear, tonic, and nonlinear phasic vestibulo-ocular response components in central vestibular neurons.

Structural Changes in the Muscle Thin Filament during Contractions Caused by Single and Double Electrical Pulses

In order to investigate the structural changes of the myofilaments involved in the phenomenon of summation in skeletal muscle contraction, we studied small-angle x-ray intensity changes during twitches of frog skeletal muscle elicited by either a single or a double stimulus at 16 °C. The separation of the pulses in the double-pulse stimulation was either 15 or 30 ms. The peak tension was more than doubled by the second stimulus. The equatorial (1,0) intensity, which decreased upon the first stimulus, further decreased with the second stimulus, indicating that more cross-bridges are formed. The meridional reflections from troponin at 1/38.5 and 1/19.2 nm − 1 were affected only slightly by the second stimulus, showing that attachment of a small number of myosin heads to actin can make a cooperative structural change. In overstretched muscle, the intensity increase of the troponin reflection in response to the second stimulus was smaller than that to the first stimulus. These results show that the summation is not due to an increased Ca binding to troponin and further suggest a highly cooperative nature of the structural changes in the thin filament that are related to the regulation of contraction.

Effects of stimulus manipulation on electrophysiological responses in pediatric cochlear implant users. Part I: Duration effects

Discrepancies between electrophysiological and behavioral thresholds in cochlear implant users might be due to differences in stimuli such as the duration and rate of the electrical pulse train. In the present study, we asked: Is there an effect of stimulus duration on electrophysiological responses of the auditory brainstem, thalamo-cortex, and behavioral thresholds? In 5 pediatric cochlear implant users, behavioral thresholds in response to electrical pulse trains at 500 pulses per second (pps) were significantly lower for 40 ms than 2 ms duration pulse trains. Clear electrically evoked auditory brainstem responses (EABR) and electrically evoked middle latency responses (EMLR) were generated by single electrical pulses and 2, 6, and 10 ms pulse trains (500 pps) in 5 children. There was a linear decrease in the inter-wave latency between the eV of the EABR and the Na of the EMLR as duration increased. No significant effect of duration was found on eV latency relative to the last pulse in the train or Na latency relative to the onset of the stimuli. Behavioral threshold data is consistent with temporal integration of auditory activity. Electrophysiological data indicates that: (a) recognizable EABR and EMLR waveforms can be recorded in response to electrical pulse trains of up to 10 ms; and (b) pulse train stimuli have unique effects on the auditory brainstem compared to thalamo-cortical areas.

Effects of stimulus manipulation on electrophysiological responses of pediatric cochlear implant users. Part II: Rate effects

Electrophysiological thresholds do not accurately predict behavioral thresholds in pediatric cochlear implant users possibly due to differences in rate and duration of pulse presentation. We asked: (1) is there an effect of rate of stimulus presentation on the electrophysiological responses of the auditory brainstem and thalamo-cortex? and (2) can the relationship between electrophysiological and behavioral thresholds be improved by using the same rate of pulse presentation? Behavioral and electrophysiological (EABR and EMLR) responses were elicited for 14 children to single electrical pulses and pulse trains of 2 ms ranging in rate from 500 to 3600 pulses per second (pps). Low rate (500 pps) pulse trains resulted in an increase in EABR wave eIII amplitude and a decrease in wave eV amplitude. Further rate increases resulted in smaller EABR wave amplitudes. EMLR amplitudes were unaffected by increases in rate as were EABR and EMLR latencies. Behavioral thresholds decreased with increasing rate, however, there was no associated reduction in electrophysiological thresholds. Correlation between behavioral and electrophysiological thresholds did not improve by using the same rate of electrical pulse stimulation. Results suggest: (1) higher rates of electrical pulse presentation increase the potential for neural adaptation in the auditory brainstem and (2) using the same rate of electrical pulse presentation does not improve the ability of EABR and EMLR thresholds to predict behavioral thresholds.

Differential Effects of Long-Term Potentiation Evoked at the CA3–CA1 Synapse before, during, and after the Acquisition of Classical Eyeblink Conditioning in Behaving Mice

Experimentally induced long-term potentiation (LTP) is a persistent increase in synaptic strength that decays across time. In contrast, changes in synaptic strength during actual learning are gradual processes that increase with training. We have studied here the effects of LTP evoked before, during, and after the acquisition of a well known associative learning paradigm: the classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus (US). A single electrical pulse was presented to the Schaffer collateral-commissural pathway to evoke field EPSPs (fEPSPs) during the CS-US interval. LTP induced by high-frequency stimulation of the Schaffer collaterals lasted for 6-10 d. When LTP was evoked before conditioning, animals were unable to acquire conditioned eyeblinks if the training started 8 d after LTP disappearance, and no change was detected in fEPSP evoked at the CA3-CA1 synapse during conditioning. In contrast, LTP-induced animals learned as did controls when the conditioning test was presented 20 d after LTP had decayed to baseline, and presented a normal increase in fEPSP slopes across conditioning. When evoked during the first two conditioning sessions, LTP prevented both eyeblink conditioning and fEPSP increase. Finally, LTP did not disrupt the normal performance of a recall test of a previously acquired eyeblink conditioning. In this latter experiment, both the LTP-induced potentiation of fEPSPs and their physiological potentiation decayed across time with a similar time constant, with no apparent effect on memory recall.

In vitro modulation of endogenous rhythms by AC electric fields: Syncing with clinical brain stimulation

Humans are exposed to an increasing prevalence of weak and strong AC electric fields, as part of daily life in the modern world. Further, electric fields are being deployed to modulate brain function for research and clinical applications. A single electric field pulse, applied via transcranial electrical or magnetic stimulation, can transiently excite or disrupt activity in neural circuits. In contrast, extended exposure to steady electric fields or pulse trains can result in long-term effects on neural activity including potentiation or depression. In addition, it has been demonstrated that brain stimulation with electric fields can improve cognitive performance in normal subjects (Marshall et al. 2006). The impact of electric fields on brain function has motivated the development of therapies to treat a wide range of psychiatric and neurological diseases using transcranial electrical or magnetic stimulation (Wassermann & Lisanby, 2001), as well as deep brain stimulation with implanted electrodes. The mechanisms by which electric fields affect brain function have not been fully elaborated. A recent report in The Journal of Physiology by Deans et al. (2007) presents new data on the interaction of AC electric fields down to a cellular level as well as with neuronal population dynamics. The report reveals a frequency-specific ability of AC electric fields to rhythmically polarize pyramidal neurons of the CA3 region of the hippocampus and demonstrates the ability of AC fields to alter pharmacologically induced endogenous oscillations in the hippocampus. These data have important implications for understanding the effect of environmental AC fields and therapeutic stimulation on the activity of neuronal ensembles. A central finding of this study is that an AC electric field, applied in vitro to a brain slice set to oscillate in the gamma frequency range through bath application of kainate, shifts the ongoing oscillation to centre on the applied field frequency or a subharmonic of that frequency. This review of Deans et al. (2007) is intended to elucidate the connection between their work and other recent in vitro findings concerning electric fields in the brain with some recent clinical findings pertaining to cognitive function and electric fields.

Resonant properties in the paddlefish electrosensory system caused by delayed feedback

The paddlefish electrosensory system consists of receptor cells in the skin that sense minute electric fields from their prey, small water fleas. The receptors thereby measure the difference of the voltage at the skin surface against the voltage inside the animal. Due to a high skin impedance, this internal voltage is considered to be relatively fixed. We found, however, that this internal voltage can fluctuate. It shows damped oscillations to a single short electric field pulse and changes, with some time delay, according to the previous history of stimulation, and shows resonance at a certain frequency. Computer simulations show that these phenomena can be explained by the presence of delayed feedback where the internal voltage is part of the feedback loop.

Catecholamine exocytosis is diminished in R6/2 Huntington’s disease model mice

In this work, the mechanisms responsible for dopamine (DA) release impairments observed previously in Huntington's disease model R6/2 mice were evaluated. Voltammetrically measured DA release evoked in striatal brain slices from 12-week old R6/2 mice by a single electrical stimulus pulse was only 19% of wild-type (WT) control mice. Iontophoresis experiments suggest that the concentration of released DA is not diluted by a larger striatal extracellular volume arising from brain atrophy, but, rather, that striatal dopaminergic terminals have a decreased capacity for DA release. This decreased capacity was not due to an altered requirement for extracellular Ca(2+), and, as in WT mice, the release in R6/2 mice required functioning vesicular transporters. Catecholamine secretion from individual vesicles was measured during exocytosis from adrenal chromaffin cells harvested from R6/2 and WT mice. While the number of exocytotic events was unchanged, the amounts released per vesicle were significantly diminished in R6/2 mice, indicating that vesicular catecholamines are present in decreased amounts. Treatment of chromaffin cells with 3-nitropropionic acid decreased the vesicular release amount from WT cells by 50%, mimicking the release observed from untreated R6/2 cells. Thus, catecholamine release from tissues isolated from R6/2 mice is diminished because of impaired vesicle loading.

Dissociation between CA3–CA1 Synaptic Plasticity and Associative Learning in TgNTRK3 Transgenic Mice

Neurotrophins and their cognate receptors might serve as feedback regulators for the efficacy of synaptic transmission. We analyzed mice overexpressing TrkC (TgNTRK3) for synaptic plasticity and the expression of glutamate receptor subunits. Animals were conditioned using a trace [conditioned stimulus (CS), tone; unconditioned stimulus (US), shock] paradigm. A single electrical pulse presented to the Schaffer collateral-commissural pathway during the CS-US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1 pyramidal cells. In wild types, fEPSP slopes increased across conditioning sessions and decreased during extinction, being linearly related to learning evolution. In contrast, fEPSPs in TgNTRK3 animals reached extremely high values, not accompanied with a proportionate increase in their learning curves. Long-term potentiation evoked in conscious TgNTRK3 was also significantly longer lasting than in wild-type mice. These functional alterations were accompanied by significant changes in NR1 and NR2B NMDA receptor subunits, with no modification of NR1(Ser 896) or NR1(Ser 897) phosphorylation. No changes of AMPA and kainate subunits were detected. Results indicate that the NT-3/TrkC cascade could regulate synaptic transmission and plasticity through modulation of glutamatergic transmission at the CA3-CA1 synapse.