Spike Amplitude Research Articles

Synchronous beta oscillation of epileptiform activities detected by microelectrode arrays in the awake and anesthetized mice

Isoflurane is a reversible anesthetic which is widely used in the surgery and animal experiments. It was still not clear whether isoflurane would affect the pattern of epileptiform signals even without seizure. In this work, an implantable and nanocomposites coated microelectrode array (MEA) was fabricated to study the neural spike firing and local field potential (LFP) in the hippocampus of awake and isoflurane anesthetized epileptic mice. The MEA recorded the neural activities during anesthesia, wakefulness and seizures at same location in the hippocampus. The results demonstrated that LFP power and neural spike firing rate were higher under anesthesia than under wakefulness. A peak appeared in the beta frequency band of epileptic LFP power distribution. There were remarkable differences in neural activities during seizures, with peak spike firing rate, amplitude and LFP power values being the largest. The epileptic animal without seizure exhibit normal behavior, but shows higher power than normal ones. The neural spike and LFP exhibited synchronous change with a similar power spectral distribution showing an epileptic peak at 11.6 Hz and higher power in the beta frequency band of 10–25 Hz. The MEA technology used in the mice brain provides an effective platform to reveal the real mechanism underlying epilepsy.

Motor activity of the biliary tract in primary sclerosing cholangitis in the clinic and experiment

The aim—to characterize violations of the motor function of the biliary system in PSC in the clinic and experiment; to reveal the morphological correspondence of the studied pathology model.Materials and methods. Under observation were 20 patients with PSC in whom the motor function of the biliary system in the clinic was studied electromyographically. The frequency and amplitude of slow waves and spikes, the power of phase and tonic contractions were recorded on the EMG curve. PLC was simulated in 28 rats when 0.1 ml of picrylsulfonic acid was retrogradely injected into the common bile duct.Results. Electromyography of the common bile duct revealed an increase in the tone of circular muscles, a proportional increase in the power of phase and tonic contractions of the gallbladder with a decrease in the amplitude characteristics of spike activity. When simulating PSC, inhibition of EMG of the common bile duct and the detection of fibrosis of the type “bulbous husk” were noted.Conclusions. A decrease in the propulsive activity of the common bile duct in patients was found. The PSC model corresponds to the characteristics of this disease in the clinic.

The second harmonic neurons in auditory midbrain of Hipposideros pratti are more tolerant to background white noise

Although acoustic communication is inevitably influenced by noise, behaviorally relevant sounds are perceived reliably. The noise-tolerant and -invariant responses of auditory neurons are thought to be the underlying mechanism. So, it is reasonable to speculate that neurons with best frequency tuned to behaviorally relevant sounds will play important role in noise-tolerant perception. Echolocating bats live in groups and emit multiple harmonic signals and analyze the returning echoes to extract information about the target features, making them prone to deal with noise in their natural habitat. The echolocation signal of Hipposideros pratti usually contains 3–4 harmonics (H1H4), the second harmonic has the highest amplitude and is thought to play an essential role during echolocation behavior. Therefore, it is reasonable to propose that neurons tuned to the H2, named the H2 neurons, can be more noise-tolerant to background noise. Taking advantage of bat's stereotypical echolocation signal and single-cell recording, our present study showed that the minimal threshold increases (12.2 dB) of H2 neurons in the auditory midbrain were comparable to increase in bat's call intensity (14.2 dB) observed in 70 dB SPL white noise condition, indicating that the H2 neurons could work as background noise monitor. The H2 neurons had higher minimal thresholds and sharper frequency tuning, which enabled them to be more tolerant to background noise. Furthermore, the H2 neurons had consistent best amplitude spikes and sharper intensity tuning in background white noise condition than in silence. Taken together, these results suggest that the H2 neurons might account for noise-tolerant perception of behaviorally relevant sounds.

Subsecond X-ray Spikes in Solar Flares: Kinematics of Acceleration and Transport of Accelerated Electrons

Hard X-rays time structure of solar flares can be caused by the timing of electrons acceleration, the kinematics of their propagation in the flaring plasma, and possible changes in plasma parameters and the loop magnetic field. In this paper the subsecond hard X-ray emission features were studied in a model of collapsing magnetic trap. The injection of 50-millisecond pulses of accelerated electrons in looptop with specified distributions of plasma density and magnetic field structure was considered. The magnetic field fluctuations and ion-acoustic turbulence influence on the fine time structure of hard X-ray emission was shown. The simulation results that it is possible to observe a super-thin time structure in the hard X-ray emission from accelerated electrons only if: ion-acoustic turbulence develops in magnetic loops and/or the pitch-angular distribution of electrons is sharply anisotropic. Moreover, the amplitude of individual spike is greater for harder electron spectra.

Late-time turbulent mixing induced by multimode Richtmyer–Meshkov instability in cylindrical geometry

Turbulent mixing induced by Richtmyer–Meshkov instability (RMI) in convergent geometry widely exists in natural phenomena and in engineering applications. In the present work, high-resolution numerical simulations of RMI at a complete cylindrical interface, with the imploding shock wave initially passing from the heavy fluid to the light fluid, are presented. Two different initial perturbations are applied. The mixing zone finally reaches a convergence ratio Cr ≈ 1.6 in both cases. Compared to classical RM instability, the more complex wave system, as well as the geometrical effect induced by the radial movement of mixing fluid, modifies the evolution of the mixing zone. The growth rate of the mixing width is analyzed in terms of the stretching or compression effect and species-penetration effect. In a cylindrical geometry, the stretching or compression effect is mainly induced by the wave system and the nonplanar geometric environment. The late-time turbulent mixing width induced by the penetration effect scales as (t−t0)θ, as with the evolution of planar RMI. For both cases, the mass-fraction profiles are collapsed at the late time if the radial coordinate is first shifted with the spike-front position and then scaled by the mixing width. By analyzing the distribution of the bubble (spike) contour, the dominant bubble (spike) diameter [D¯b(s)] is obtained. The ratios [βb(s)] between the dominant bubble (spike) diameter and the bubble (spike) amplitude [Wb(s)] are calculated, and a stable ratio of spike βs is observed during the late stage. Meanwhile, the ratio of the bubble βb is greater than 1 at late time.

Perpendicular Spin-Torque-Transfer Mechanism of Neuron: Integrate Vs. Stochastic Nature

Achieving a higher integration density and a lower power consumption for neuromorphic devices, recently, spin neuron has been intensively researched. [ref . 1-3] In particular, 2-terminal perpendicular spin-transfer-torque (p-STT) neuron has been reported as a candidate of spin neuron. [ref 4-5] This neuron showed both stochastic nature as well as integrate nature, which is determined by reset voltage and spike amplitude (i.e. set voltage). However, the mechanisms between two different neuron nature has not been clearly proved.Here, two different mechanisms were reviewed by observing the dependency of neuron nature on reset voltage and spike amplitude. 2-terminal p-STT neuron, as shown in Fig. 1(a), was operated by two different reset voltage and spike amplitude (i.e. fully reset or partially reset) dislike p-STT MRAM, as shown in Fig. 1(b). Two different reset voltage and spike amplitude would have a different energy distribution from parallel state to anti-parallel state for integrate or stochastic nature; i.e. the energy level of parallel state for partially reset was higher than that for fully reset and the activation energy (i.e. parallel to anti-parallel state switching) for partially reset was lower than that for fully reset, as shown in Fig. 1(c).For fully reset case, the probability of switching from parallel to anti-parallel increased with the spike amplitude (i.e. negative bias magnitude) being able to produce a sigmoid function for stochastic neuron, as shown in Figs. 1(d)-(h). Otherwise, for partially reset case, the resistance margin between parallel and anti-parallel state was enhanced with the spike amplitude, being able to reduce a read error rate in fire circuit, as shown in Figs. 1(i)-(m). In addition, in our presentation, we will review in detail to different mechanism between integrate and stochastic nature by the grain size distribution of the MgO tunneling barrier in p-STT neurons. Particularly, it was found that a criteria between integrate and stochastic nature in p-STT neurons could be decided by the reset voltage amplitude; i.e. the ratio of stochastic (i.e. fully reset) to integrate (i.e. partially reset) decreased with increasing the reset voltage amplitude. ACKNOWLEDGEMENT This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2016M3A7B4910249)and the Brain Korea 21 PLUS Program in 2014. REFERENCE [1] Sengupta, Abhronil, and Kaushik Roy. "Spin-transfer torque magnetic neuron for low power neuromorphic computing." 2015 International Joint Conference on Neural Networks (IJCNN). IEEE, 2015.[2] Krzysteczko, Patryk, et al. "The Memristive Magnetic Tunnel Junction as a Nanoscopic Synapse‐Neuron System." Advanced Materials 24.6 (2012): 762-766.[3] Borders, William A., et al. "Analogue spin–orbit torque device for artificial-neural-network-based associative memory operation." Applied physics express 10.1 (2016): 013007.[4] Kondo, Kei, et al. "A two-terminal perpendicular spin-transfer torque based artificial neuron." Journal of Physics D: Applied Physics 51.50 (2018): 504002.[5] Kim, Dong Won, et al. "Double MgO-Based Perpendicular Magnetic Tunnel Junction for Artificial Neuron." Frontiers in Neuroscience 14 (2020). Figure 1

Al2O3-Based Capacitor-Less Conductive-Bridge Neuron Having Negative-Differential-Resistance

Recently, memristive devices (e.g. CBRAM and ReRAM etc.) have been proposed as an alternative to C-MOSFET based neuromorphic device (i.e. neuron and synapse) to achieve a high neuronal density and low power consumption. Among memristive devices, the conductive bridge neuron has been a great attention due to its area efficiency, low power consumption (< 500 fJ), and good C-MOS compatibility 1-3 . However, past researches have mainly focused on stochastic nature of conductive-bridge neurons. In particular, most of the stochastic conductive-bridge neuron have used capacitors to implement membrane potential, which requires a large integration area (~1000F2). In this works, integrate property of Al2O3-based cap-less conductive-bridge neuron was demonstrated which allows a cost-efficient neuromorphic chip by using a same process technology as a memristor synapse, as shown in Fig 1 (a). Note that the Al2O3-based cap-less conductive-bridge neuron was the same as that of the Al2O3-based memristor synapse. In addition, we investigated the effect of negative-differential-resistance (NDR) characteristic on integrate property for our proposed neuron, depending on the compliance current level (i.e. a shape of metallic filaments in neuron device).The NDR slope was adjusted by varying a compliance current of a Al2O3-based cap-less conductive-bridge neuron. The current compliance (Icc) of 1 mA showed the NDR slope of ~ 0.56 decade/V, as shown in Fig. 1(b). For all spike amplitude (i.e. -0.6~-1.0 V), the resistances of neuron device abruptly increased at a certain number of spikes, depending on the spike amplitude, and then it gradually increased with the number of spikes, as shown in Fig. 1(c). In addition, the spike number being necessary for achieving ~600 Ω decreased exponentially with increasing the number of spikes, as showed integrate property depending on input spike amplitude, as shown in Fig. 1(d). Otherwise, the current compliance (Icc) of 0.1 mA, which was 10 times less than Fig 1 (b) presented the NDR slope of ~ 0.23 decade/V, which was 2 times less than Fig. 1(b), as shown in Fig. 1(e). For all spikes amplitude, the resistance of neuron devices gradually increased with the number of spikes, wherein the resistance of neuron devices increased with the spike amplitude (i.e. negative voltage pulse amplitude), as shown in Fig. 1(f). The spike number being necessary for achieving ~10 kΩ decreased exponentially with increasing the number of spikes, as shown in Fig. 1(g). Comparing Fig. 1(d) with Fig. 1(g), the variation of the spike number being necessary for achieving ~600 Ω for the NDR slope of ~-0.56 decade/V was much less that for the spike number being necessary for achieving ~10 kΩ for the NDR slope of ~-0.23 decade/V. This result indicates that, for the Al2O3-based cap-less conductive-bridge neuron, the NDR slope dominantly determines the integrate nature. In our presentation, we will discuss the mechanism why the integrate property depended on the NDR slope via understanding a shape of conductive-metallic-filaments in Al2O3 layer, which determine an integrate property of neuron devices. In particular, it will be reported that the shape of conductive-metallic-filaments strongly depended on the metal vacancy concentration in binary oxide (i.e. Al2O3) layer. Acknowledgement This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIT) (No. 2016M3A7B4910249). Reference "IEEE Transactions on Emerging Topics in Computational Intelligence," in IEEE Transactions on Emerging Topics in Computational Intelligence, vol. 2, no. 5, pp. C2-C2, Oct. 2018, doi: 10.1109/TETCI.2018.2867377.Jang, B. Attarimashalkoubeh, A. Prakash, H. Hwang and Y. Jeong, "Scalable Neuron Circuit Using Conductive-Bridge RAM for Pattern Reconstructions," in IEEE Transactions on Electron Devices, vol. 63, no. 6, pp. 2610-2613, June 2016, doi: 10.1109/TED.2016.2549359.Palma, M. Suri, D. Querlioz, E. Vianello and B. De Salvo, "Stochastic neuron design using conductive bridge RAM," 2013 IEEE/ACM International Symposium on Nanoscale Architectures (NANOARCH), Brooklyn, NY, 2013, pp. 95-100, doi: 10.1109/NanoArch.2013.6623051. Figure 1

Integrate Nature of Perpendicular Spin-Orbit-Torque Neuron Depending on Crystal Structure of Tungsten

With the expanding use of artificial intelligence (AI), a higher integration density and lower power consumption is required of the neuromorphic devices. In particular, 2-terminal perpendicular spin-transfer-torque (p-STT) neuron has been reported as a candidate of spin neuron. [1-2] However, p-STT devices cannot reliably operate at ns and sub-ns scale because of large incubation delays. [3] In addition, the shared read/write path compromise the read reliability where the write operation can impose severe stress to the MgO tunneling barrier, leading to a possible time dependent degradation of the p-MTJ spin-valve. As a solution to these issues, Spin-Orbit-Torque (SOT) based MRAM was proposed where the read/write path is separated.The crystallinity of the W film used for SOT channel ex-situ annealed at 350oC was investigated depending on the W thickness from 4 to 10 nm, as shown in Figs. 1(a) and (b), where the transition from β (A15 crystal structure) to α-phase (b.c.c.) occurs between thickness of 5-nm and 6-nm. Also, the resistivity of the W film was greatly reduced from 150 to 40 Ω cm at this thickness which further shows the transition from β to α-phase, as shown in Fig. 1(c). The the b.c.c. (110) crystallinity can be confirmed in the 6-nm thick W, as shown in Fig. 1(d). In our sample, β-phase tungsten was confirmed below 6-nm at ex-situ annealing temperature of 350oC which is known to have the highest SOT efficiency (>0.3) [4]. The p-SOT neuron was patterned into a hall-bar to confirm the SOT efficiency depending on the crystal structure of the W film, as shown in Fig. 1(e). The hysteresis loop showed perpendicular magnetic anisotropy for both 4 and 6-nm W, but the change of the Hall resistance was negligible in the case of 6-nm W thick p-SOT neuron, as shown in Fig. 1(f). The normalized Hall resistance was measured as a function of nearly in-plane magnetic field (β=4o: angle between external field and injected current) under a positive or negative current (±1 mA) to calulate the spin-torque per magnetic moment (τST), as shown in Figs. 1(i)-(k), where the slope of [B+(θ)-B-(θ)] is τST. The τST increases with applied current for both α and β-phase W, but the spin torque of α-phase is about 1/3 of the β-phase W. In addition, the spin hall angle of the β-phase W (-0.288) was about 6 times larger than that of the α-phase W (-0.045), as shown in Fig. 1(l). In our presentation, we will review in detail the integrate nature of the p-SOT neuron depending on the spike amplitude and crystal structure of the W. Acknowledgement *This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2016M3A7B4910249) and the Brain Korea 21 PLUS Program in 2014. Reference [1] Kondo, K., Choi, J., Baek, J., and Jun, H. A two-terminal perpendicular spin-transfer torque based artificial neuron. J. Phys. D Appl. Phys. 51:504002. (2018)[2] Dong Won Kim, et al. Double MgO-Based Perpendicular Magnetic Tunnel Junction for Artificial Neuron. Front. Neurosci. 14:309 (2020)[3] Ya-Jui Tsou, Jih-Chao Chiu, Huan-Chi Shih, Chee Wee Liu, Write Margin Analysis of Spin–Orbit Torque Switching Using Field-Assisted Method, Exploratory Solid-State Computational Devices and Circuits IEEE Journal on, vol. 5, no. 2, pp. 173-181, 2019.[4] Qiang Hao and Gang Xiao, Giant Spin Hall Effect and Switching Induced by Spin-Transfer Torque in a W/Co40Fe40B20/MgO Structure with Perpendicular Magnetic Anisotropy, PHYS. REV. APPLIED 3, 034009 (2015) Figure 1

MgO-Tunneling-Barrier Crystallinity Influence on Resistance Sensing Margin for Spiking Neuron Having Perpendicular-Spin-Transfer-Torque Integrate Characteristic

The application fields of artificial intelligence (AI) has been widely expanded; security, finance, health care, etc. A conventional neuromorphic chips for AI has been fabricated with synapse array and neuron integration using C-MOSFET technology, having a scaling-down limit of neuromorphic chips because of a large neuron size and producing a high power consumption. In particular, as an alternative solution for scaling-down neuron, 2-terminal perpendicular-spin-transfer-torque (p-STT) neuron has been proposed [1], [2]. In this neuron, the face –centered-cubic (f.c.c) crystallinity of a MgO tunneling barrier is an extremely critical parameter to determine the integrate characteristic of a neuron. In our study, we investigated how the f.c.c crystallinity of MgO tunneling barrier influenced the resistance sensing margin for integrate characteristic in 2-terminal p-STT neuron. The f.c.c crystallinity of MgO tunneling barrier strongly depended on the RF sputtering power to sputter 1.15-nm-thick MgO tunneling barrier, as shown in Fig.1(a). The resistance difference between anti-parallel (AP) state and parallel (P) state increased with the RF sputtering power as shown in Fig.1(b). The better sequence of the f.c.c crystallinity of the MgO tunneling barrier was followed by 320, 350, 290, and 260 Watt, as shown in Fig. 1(c). The dependency of the f.c.c crystalliny of the MgO tunneling barrier RF sputtering power will be explained by crystalline defect distribution using spectroscopy ellipsometer. In addition, we examined the f.c.c crystallnitiy of the MgO tunneling barrier influence on the resistance sensing margin for integrate characteristic of neuron, as shown in Figs.1(d)-(g). Note that, in our experiment, the integrate characteristics of p-STT neuron was measured after a partially reset. The resistance sensing margin clearly increased with the f.c.c crystallinity of the MgO tunneling barrier in p-STT neuron and evidently increased with the input spike amplitude. In particular, an assure clarification of a resistance margin depending on the input spike amplitude could be achieved above the f.c.c crystallinity of the MgO tunneling barrier sputtered at 320 and 350 Watt. In out presentation, we will demonstrate the mechanism why the integrate characteristic of the neuron mainly depended on the f.c.c crystallinity of the MgO tunneling barrier by reviewing p-STT switching at a MgO tunneling barrier having a nanoscale-diameter MgO grain which affects the activation energy barrier for p-STT switching.Reference[1] Kondo, K., Choi, J., Baek, J., and Jun, H. (2018). A two-terminal perpendicular spin-transfer torque based artificial neuron. J. Phys. D Appl. Phys. 51:504002.[2] Dong Won Kim, Woo Seok Yi, Jun Young Choi, Kei Ashiba, Jong Ung Baek, Han Sol Jun, Jae Joon Kim and Jea Gun Park (2020)AcknowledgementThis work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2016M3A7B4910249)and the Brain Korea 21 PLUS Program in 2014. . Figure 1

Cardiotoxicity induced by the combination therapy of chloroquine and azithromycin in human embryonic stem cell-derived cardiomyocytes

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs.

Low corticosterone levels attenuate late life depression and enhance glutamatergic neurotransmission in female rats.

Sustained elevation of corticosterone (CORT) is one of the common causes of aging and major depression disorder. However, the role of elevated CORT in late life depression (LLD) has not been elucidated. In this study, 18-month-old female rats were subjected to bilateral adrenalectomy or sham surgery. Their CORT levels in plasma were adjusted by CORT replacement and the rats were divided into high-level CORT (H-CORT), low-level CORT (L-CORT), and Sham group. We showed that L-CORT rats displayed attenuated depressive symptoms and memory defects in behavioral tests as compared with Sham or H-CORT rats. Furthermore, we showed that glutamatergic transmission was enhanced in L-CORT rats, evidenced by enhanced population spike amplitude (PSA) recorded from the dentate gyrus of hippocampus in vivo and increased glutamate release from hippocampal synaptosomes caused by high frequency stimulation or CORT exposure. Intracerebroventricular injection of an enzymatic glutamate scavenger system, glutamic-pyruvic transmine (GPT, 1 μM), significantly increased the PSA in Sham rats, suggesting that extracelluar accumulation of glutamate might bethe culprit of impaired glutamatergic transmission, which was dependent on the uptake by Glt-1 in astrocytes. We revealed that hippocampal Glt-1 expression level in the L-CORT rats was much higher than in Sham and H-CORT rats. In a gradient neuron-astrocyte coculture, we found that the expression of Glt-1 was decreased with the increase of neural percentage, suggesting that impairment of Glt-1 might result from the high level of CORT contributed neural damage. In sham rats, administration of DHK that inhibited Glt-1 activity induced significant LLD symptoms, whereas administration of RIL that promoted glutamate uptake significantly attenuated LLD. All of these results suggest that glutamatergic transmission impairment is one of important pathogenesis in LLD induced by high level of CORT, which provide promising clues for the treatment of LLD.

Physical exercise and 5-hydroxytryptophan, a precursor for serotonin synthesis, reduce penicillin-induced epileptiform activity

AimPrevious studies have shown that 5- hydroxytryptophan (5-HTP) and exercise play an important role in the synthesis of serotonin independently. The effects of the treadmill exercise and 5‐ hydroxytryptophan (5-HTP) on seizure mechanisms created by epileptiform activity with penicillin model were investigated in rats. MethodA total of 28 male albino Wistar rats were randomly divided into four groups: exercise (Ex), Control (Cnt), 5‐hydroxytryptophan (5htp) and 5-hydroxytryptophan + exercise (5htpEx) groups. Treadmill exercise and gavage (25 mg/kg/day) were administered five days a week for ten weeks. Electrocorticogram data were recorded for 3 h at the end of the protocol using the Power-Lab data acquisition system. Spike frequency, amplitude, and latency time were analyzed offline. The significant differences among the groups were evaluated by one-way analysis of variance (ANOVA). ResultsSpike frequency was observed at the highest level from the 20th minute in the Cnt group, and this continued until the end of the recording. The 5-HTP alone group did not affect epileptiform activity. At the 80th minute of penicillin injection, the epileptiform activity in the 5htpEx group decreased significantly compared with the Cnt, and this significance continued until the 110th minute. There was no statistical difference in the amplitude values of the groups. The 5htpEx group was significantly higher than both the Cnt and Ex group in the seizure latency times. ConclusionsIt was determined that exercise reduced the spike number and delayed seizure significantly by potentiating the effect of 5-HTP. Given that 5-HTP used in combination with exercise can perform useful actions such as reducing seizure sensitivity and consequently improving the quality of life for individuals with epilepsy, it may be a potential candidate for the treatment of epilepsy in nonpharmacological methods.

Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium–pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE.

Axonal mechanisms mediating γ-aminobutyric acid receptor type A (GABA-A) inhibition of striatal dopamine release.

Axons of dopaminergic neurons innervate the striatum where they contribute to movement and reinforcement learning. Past work has shown that striatal GABA tonically inhibits dopamine release, but whether GABA-A receptors directly modulate transmission or act indirectly through circuit elements is unresolved. Here, we use whole-cell and perforated-patch recordings to test for GABA-A receptors on the main dopaminergic neuron axons and branching processes within the striatum of adult mice. Application of GABA depolarized axons, but also decreased the amplitude of axonal spikes, limited propagation and reduced striatal dopamine release. The mechanism of inhibition involved sodium channel inactivation and shunting. Lastly, we show the positive allosteric modulator diazepam enhanced GABA-A currents on dopaminergic axons and directly inhibited release, but also likely acts by reducing excitation from cholinergic interneurons. Thus, we reveal the mechanisms of GABA-A receptor modulation of dopamine release and provide new insights into the actions of benzodiazepines within the striatum.

The T-type calcium channel isoform Cav3.1 is a target for the hypnotic effect of the anaesthetic neurosteroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile

BackgroundThe mechanisms underlying the role of T-type calcium channels (T-channels) in thalamocortical excitability and oscillations in vivo during neurosteroid-induced hypnosis are largely unknown. MethodsWe used patch-clamp electrophysiological recordings from acute brain slices ex vivo, recordings of local field potentials (LFPs) from the central medial thalamic nucleus in vivo, and wild-type (WT) and Cav3.1 knock-out mice to investigate the molecular mechanisms of hypnosis induced by the neurosteroid analogue (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH). ResultsPatch-clamp recordings showed that 3β-OH inhibited isolated T-currents but had no effect on phasic or tonic γ-aminobutyric acid A currents. Also in acute brain slices, 3β-OH inhibited the spike firing mode more profoundly in WT than in Cav3.1 knockout mice. Furthermore, 3β-OH significantly hyperpolarised neurones, reduced the amplitudes of low threshold spikes, and diminished rebound burst firing only in WT mice. We found that 80 mg kg−1 i.p. injections of 3β-OH induced hypnosis in >60% of WT mice but failed to induce hypnosis in the majority of mutant mice. A subhypnotic dose of 3β-OH (20 mg kg−1 i.p.) accelerated induction of hypnosis by isoflurane only in WT mice, but had similar effects on the maintenance of isoflurane-induced hypnosis in both WT and Cav3.1 knockout mice. In vivo recordings of LFPs showed that a hypnotic dose of 3β-OH increased δ, θ, α, and β oscillations in WT mice in comparison with Cav3.1 knock-out mice. ConclusionsThe Cav3.1 T-channel isoform is critical for diminished thalamocortical excitability and oscillations that underlie neurosteroid-induced hypnosis.

Quad Code Sequence Generation Using Cyclic Redundancy Technique to Enhance Target Detection in Doppler Rader

Today’s world is contemplating to set the new developments in radar to face the security challenges in defense. In the scope of radar signal processing, technical expertise in the signal processing, coding theory and techniques brought a lot of exposers to improve the detection probability in terms of range and position. The present art of work focusing on the detection of multiple moving targets using Doppler radar. Though the existing approaches try to increase the Merit Factor and range resolution of the acquired Signal, As such methods fail to find out the target when they are in multiple and moving, due to which the amplitude of the side spikes (Noise) is much more with respect to the highest detectable limit. Those side spikes dominate the probability of detection of a target because the weak echoes from the small targets may be masked by these side spikes of huge moving targets. This recommended approach provides clear information about the targets with respect to Doppler by creating multiple clear windows at various Doppler's with respect to the range. The amplitude of all windows is below 85–90 dB down, so all moving targets can be easily detected. This approach is validating by the use of Mat lab.

Electrophysiological Alterations of Pyramidal Cells and Interneurons of the CA1 Region of the Hippocampus in a Novel Mouse Model of Dravet Syndrome.

Dravet syndrome is a developmental epileptic encephalopathy caused by pathogenic variation in SCN1A To characterize the pathogenic substitution (p.H939R) of a local individual with Dravet syndrome, fibroblast cells from the individual were reprogrammed to pluripotent stem cells and differentiated into neurons. Sodium currents of these neurons were compared with healthy control induced neurons. A novel Scn1aH939R/+ mouse model was generated with the p.H939R substitution. Immunohistochemistry and electrophysiological experiments were performed on hippocampal slices of Scn1aH939R/+ mice. We found that the sodium currents recorded in the proband-induced neurons were significantly smaller and slower compared to wild type (WT). The resting membrane potential and spike amplitude were significantly depolarized in the proband-induced neurons. Similar differences in resting membrane potential and spike amplitude were observed in the interneurons of the hippocampus of Scn1aH939R/+ mice. The Scn1aH939R/+ mice showed the characteristic features of a Dravet-like phenotype: increased mortality and both spontaneous and heat-induced seizures. Immunohistochemistry showed a reduction in amount of parvalbumin and vesicular acetylcholine transporter in the hippocampus of Scn1aH939R/+ compared to WT mice. Overall, these results underline hyper-excitability of the hippocampal CA1 circuit of this novel mouse model of Dravet syndrome which, under certain conditions, such as temperature, can trigger seizure activity. This hyper-excitability is due to the altered electrophysiological properties of pyramidal neurons and interneurons which are caused by the dysfunction of the sodium channel bearing the p.H939R substitution. This novel Dravet syndrome model also highlights the reduction in acetylcholine and the contribution of pyramidal cells, in addition to interneurons, to network hyper-excitability.

Detonation properties of the mixtures of tetranitromethane/methanol and tetranitromethane/nitrobenzene

In this work, the reaction zone structure, stability of detonation waves and limits of detonation propagation in the mixtures of tetranitromethane/methanol and tetranitromethane/nitrobenzene depending on the diluent concentration, were studied by a VISAR laser interferometer with a nanosecond time resolution. In the experiments, a sharp change in the reaction zone at the concentration of diluents in the vicinity of stoichiometry is observed – the amplitude of von Neumann spike decreases significantly. This is due to an increase in the initial reaction rate, which leads to the decomposition of HE directly in the shock wave front. It was found that the addition of diluent resulted in an increase in the detonation velocity of the tetranitromethane/diluent mixture in the vicinity of the stoichiometric concentration (about 25% of methanol or nitrobenzene). In almost the entire concentration range, the detonation waves are stable with respect to the formation of the cellular structure of the front. At the same time, in the range of diluent concentration of 15-35%, a poor reproducibility of the amplitude values of the particle velocity from shot to shot is observed. This is probably due to the longitudinal instability of the detonation waves in the mixture.

Abstract 397: Differentiation and Maturation of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes in Nanopatterned Cell Culture

Background: Human induced pluripotent stem cells (hiPSCs) are widely used in studies of developmental and regenerative biomedicine involving various cell types, including cardiomyocytes (CMs). Understanding the cellular and molecular processes during hiPSC-CM differentiation and maturation will be crucial to develop heart regeneration therapies. In addition, while bioengineered cellular cues have been shown to modulate cellular morphology and phenotypes, little is known regarding their effects on molecular and functional maturity of hiPSC-CMs. Aims: To determine the expression of cardiac and cell cycle genes and the electrophysiological properties of hiPSC-CMs during their differentiation and maturation on unpatterned (Flat) or isotropic/nanopatterned (Nano) cell culture surface. Methods and Results: Using small molecules, WTC-11 hiPSC were differentiated into CMs efficiently (92.5% TNNT2 + ; 95% NKX2-5 + ). The resultant hiPSC-CMs were re-plated in Flat or Nano surfaces and harvested at different time points. Cardiac genes Myh7, Tnnt2, Serca2a, Ryr2, Cacna1c , and Kcnj2 gradually and significantly increased during differentiation; this was accompanied by reduced expression of cell cycle genes. While myofilament genes expressions were similar between Nano and Flat cultured hiPSC-CMs, ion channel genes Scn5a, Cacna1c , and Kcnj2 were significantly higher in Nano group, suggesting that Nano cultured CMs were more matured. In addition, fewer hiPSC-CMs were proliferative (EdU + ) in 2-week Nano group compared to Flat group. This was associated with decreased expression of active cell cycle genes Ccne1, Cdk4, Cdk14, Ki67 and Plk1 in Nano 2-week CMs. Micro-electrode array (MEA) analysis demonstrated that Beat Period, Spike Amplitude, and Field Potential Duration were increased in the Nano group. Fluo-4 Ca 2+ imaging assay revealed improved Ca 2+ transition activities in isotropically cultured hiPSC-CMs. Conclusion: These results demonstrate a significant upregulation of cardiac genes along with a down-regulation of cell cycle genes during the differentiation and maturation of hiPSC-CM on Nano surfaces. Bioengineered nanotopographically patterned substrates promoted the maturation and electrophysiological functions of hiPSC-CMs.

Dorsal Column Nuclei Neural Signal Features Permit Robust Machine-Learning of Natural Tactile- and Proprioception-Dominated Stimuli.

Neural prostheses enable users to effect movement through a variety of actuators by translating brain signals into movement control signals. However, to achieve more natural limb movements from these devices, the restoration of somatosensory feedback is required. We used feature-learnability, a machine-learning approach, to assess signal features for their capacity to enhance decoding performance of neural signals evoked by natural tactile and proprioceptive somatosensory stimuli, recorded from the surface of the dorsal column nuclei (DCN) in urethane-anesthetized rats. The highest performing individual feature, spike amplitude, classified somatosensory DCN signals with 70% accuracy. The highest accuracy achieved was 87% using 13 features that were extracted from both high and low-frequency (LF) bands of DCN signals. In general, high-frequency (HF) features contained the most information about peripheral somatosensory events, but when features were acquired from short time-windows, classification accuracy was significantly improved by adding LF features to the feature set. We found that proprioception-dominated stimuli generalize across animals better than tactile-dominated stimuli, and we demonstrate how information that signal features contribute to neural decoding changes over the time-course of dynamic somatosensory events. These findings may inform the biomimetic design of artificial stimuli that can activate the DCN to substitute somatosensory feedback. Although, we investigated somatosensory structures, the feature set we investigated may also prove useful for decoding other (e.g., motor) neural signals.