Spike Amplitude Research Articles

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons.

Many hippocampal CA1 pyramidal cells function as place cells, increasing their firing rate when a specific place field is traversed. The dependence of CA1 place cell firing on position within the place field is asymmetric. We investigated the source of this asymmetry by injecting triangular depolarizing current ramps to approximate the spatially tuned, temporally diffuse depolarizing synaptic input received by these neurons while traversing a place field. Ramps were applied to CA1 pyramidal neurons from male rats in vitro (slice electrophysiology) and in silico (multicompartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared with somatic ramps. We incorporated a four-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in the closed state, which comprises the available pool. PKC activator phorbol-dibutyrate, known to reduce NaV long-term inactivation, removed spike amplitude attenuation in vitro more visibly in dendrites and greatly reduced adaptation, consistent with our hypothesized mechanism. Intracellular application of a peptide inducing long-term NaV inactivation elicited spike amplitude attenuation during spike trains in the soma and greatly enhanced adaptation. Our synergistic experimental/computational approach shows that long-term inactivation of NaV1.6 is a key mechanism of adaptation in CA1 pyramidal cells.SIGNIFICANCE STATEMENT The hippocampus plays an important role in certain types of memory, in part through context-specific firing of "place cells"; these cells were first identified in rodents as being particularly active when an animal is in a specific location in an environment, called the place field of that neuron. In this in vitro/in silico study, we found that long-term inactivation of sodium channels causes adaptation in the firing rate that could potentially skew the firing of CA1 hippocampal pyramidal neurons earlier within a place field. A computational model of the sodium channel revealed differential regulation of spike frequency and amplitude by long-term inactivation, which may be a general mechanism for spike frequency adaptation in the CNS.

PtNPs/Short MWCNT-PEDOT: PSS-Modified Microelectrode Array to Detect Neuronal Firing Patterns in the Dorsal Raphe Nucleus and Hippocampus of Insomnia Rats.

Research on the intracerebral mechanism of insomnia induced by serotonin (5-HT) deficiency is indispensable. In order to explore the effect of 5-HT deficiency-induced insomnia on brain regions related to memory in rats, we designed and fabricated a microelectrode array that simultaneously detects the electrical activity of the dorsal raphe nucleus (DRN) and hippocampus in normal, insomnia and recovery rats in vivo. In the DRN and hippocampus of insomnia rats, our results showed that the spike amplitudes decreased by 40.16 and 57.92%, the spike repolarization slope decreased by 44.64 and 48.59%, and the spiking rate increased by 66.81 and 63.40%. On a mesoscopic scale, the increased firing rates of individual neurons led to an increased δ wave power. In the DRN and hippocampus of insomnia rats, the δ wave power increased by 57.57 and 67.75%. Furthermore, two segments’ δ wave slopes were also increased in two brain regions of the insomnia rats. Our findings suggest that 5-HT deficiency causes the hyperactivity of neurons in the hippocampus and DRN; the DRN’s firing rate and the hippocampal neuronal amplitude reflect insomnia in rats more effectively. Further studies on alleviating neurons affected by 5-HT deficiency and on achieving a highly effective treatment for insomnia by the microelectrode array are needed.

Somatovisceral Convergence in Sleep-Wake Cycle: Transmitting Different Types of Information via the Same Pathway.

Convergence of somatic and visceral inputs occurs at the levels of nervous system ranging from spinal cord to cerebral cortex. This anatomical organization gave explanation to a referred pain phenomenon. However, it also presents a problem: How does the brain know what information is coming for processing-somatic or visceral - if both are transferred by the same spinal cord fibers by means of the standard neuronal spikes? Recent studies provided evidence for cortical processing of interoceptive information largely occurring in sleep, when somatosensation is suppressed, and for the corresponding functional brain networks rearrangement. We suggest that convergent units of the spinal cord would be able to collectively provide mainly somatosensory information in wakefulness and mainly visceral in sleep, solving the puzzle of somatovisceral convergence. We recorded spiking activity from the spinal cord lemniscus pathway during multiple sleep-wake cycles in freely behaving rabbits. In wakefulness high increased spiking corresponded to movements. When animals stopped moving this activity ceased, the fibers remained silent during passive wakefulness. However, upon transition to sleep fibers began firing again. Analysis of spiking patterns of individual fibers revealed that in the majority of them spiking rates recovered in slow wave sleep. Thus, despite cessation of motion and a corresponding decrease of somatic component of the convergent signal, considerable ascending signaling occurs during sleep, that is likely to be visceral. We also recorded evoked responses of the lemniscus pathway to innocuous electrostimulation of the abdominal viscera, and uncovered the existence of two groups of responses depending upon the state of vigilance. Response from an individual fiber could be detected either during wakefulness or in sleep, but not in both states. Wakefulness-responsive group had lower spiking rates in wakefulness and almost stopped spiking in sleep. Sleep-responsive retained substantial spiking during sleep. These groups also differed in spike amplitudes, indicative of fiber diameter differences; however, both had somatic responses during wakefulness. We suggest a mechanism that utilizes differences in somatic and visceral activities to extract both types of information by varying transmission thresholds, and discuss the implications of this mechanism on functional networks under normal and pathological conditions.

Development and initial testing of valves opened by Valsalva (abdominal straining): Proof of principle for urinary catheters or male urethra

We hypothesised that raising the abdominal pressure could provide a non-manual approach to opening a urinary valve, with potential application for indwelling catheters or an intraurethral device. The ‘Vysera’ valve remains closed during short high amplitude spikes but opens when a pre-defined low-amplitude pressure is maintained for a pre-specified duration, allowing sustained abdominal straining to achieve voluntary opening. The valve was subjected to in vitro performance and microbiological tests. Parameters for valve specification were selected by review of a large urodynamic database with nominal opening pressure of 75 cmH2O ＋/−15 cmH2O (range 60–90 cmH2O) and valve pressure was refined using early clinical results. Valve housings were designed for the end of a Foley catheter, and for male post-prostatectomy intraurethral placement. Preliminary clinical evaluation was undertaken for both designs, incorporating qualitative feedback. In vitro testing of the catheter valve demonstrated only minimal encrustation. On clinical evaluation of the catheter-sited valve, six of seven patients (86%) were able to open the valve intentionally by straining. When inactive, none of the patients experienced leakage (7/7 = 100%), while five (71%) leaked when they coughed. The intraurethral device was successfully placed with image intensifier guidance under general anaesthetic in five of nine patients. Three patients used the device; initial leakage resolved as patients mobilised. However, in contrast to the catheter-sited valve, the intraurethral device was difficult to tolerate for even a few hours. Removal was performed under local anaesthesia with a flexible cystoscope and stent grasper. We conclude that storage and bladder emptying using a strain-activated valve are feasible for a catheter valve and an intra-urethral device. The valve parameters need to be matched to individual patients. For the intraurethral device, additional development is needed to improve the stent housing and valve performance.

The effect of different exercise training modes on dentate gyrus neurodegeneration and synaptic plasticity in morphine-dependent rats

Various impacts of exercise on brain performance following the induction of morphine dependence have been documented; however, the underlying neuronal mechanisms are still unclear. The present research was done to investigate the impact of different exercise training modes on apoptosis, neuronal maturation, and synaptic plasticity in the perforant pathway (PP)-dentate gyrus (DG) synapses in the morphine-dependent rats. Five groups, including a control group (Con, ten healthy rats) and forty morphine-dependent rats were considered as follows (n = 10/group): 1) sedentary-dependent (Sed-D); 2) endurance exercise-dependent (En-D); 3) strength exercise-dependent (St-D); and 4) concurrent exercise-dependent (Co-D). The exercise training groups were subjected to endurance, strength, and concurrent training five days a week for ten weeks. After training sessions, the field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude in the DG were determined in response to high-frequency stimulation (HFS) of the PP. For assessing neurogenesis and apoptosis, NeuroD and Caspase-3 expression levels were evaluated after all experiments. Concurrent training increased PS amplitude and EPSP compared to the control group. NeuroD in the morphine-dependent rats significantly decreased, but concurrent training returned the NeuroD to its levels in healthy rats. Furthermore, Caspase-3 expression levels in morphine-dependent rats remarkably increased and concurrent training significantly reduced Caspase-3 expression levels compared to the Sed-D group. Concurrent training can ameliorate synaptic plasticity impairment in morphine-dependent rats through neurogenesis promotion and apoptosis reduction. According to the results, concurrent training can be an appropriate novel candidate for treating opioid addiction.

Impairment of spatial memory and dorsal hippocampal synaptic plasticity in adulthood due to adolescent morphine exposure

Opioid exposure during adolescence, a crucial period of neurodevelopment, has lasting neurological and behavioral consequences and affects the cognitive functions in adulthood. This study investigated the effects of adolescent morphine exposure in spatial learning and memory and synaptic plasticity of the CA1 area of the dorsal hippocampus.Adolescent Wistar rats received increasing doses of morphine for 1, 5, and 10 days. Acute morphine group was injected 2.5 mg/kg morphine for 1 day, subchronic morphine group for 5 days, with an increasing dose of 2.5 mg/kg and reached to the dose of 12.5 mg/kg and chronic morphine group for 10 days that began with an increasing dose of 2.5 mg/kg and reached to the dose of 25 mg/kg. Then after 25 days and reaching adulthood, spatial learning and memory were evaluated via the Morris water maze (MWM) test. Moreover, we test the electrophysiological properties of dorsal hippocampal plasticity in adult rats by in vitro field potential recordings.Subchronic and chronic adolescent morphine exposure impaired spatial learning and memory in the MWM test. Baseline synaptic responses in the chronic morphine group were increased and long-term potentiation (LTP) impaired in the CA1 area in subchronic and chronic morphine groups. In adulthood, the slope of the field excitatory postsynaptic potential (fEPSP) required to elicit a half-maximal population spike (PS) amplitude was significantly larger in subchronic and chronic adolescent morphine exposure compared to the saline group. Therefore, subchronic and chronic adolescent morphine exposure altered synaptic transmission and plasticity in addition to learning and memory.Long-term morphine exposure during adolescence can interfere with neurodevelopment, making a persistent impression on plasticity and cognitive capability in adulthood.

확률적 정보량에 의한 표면근전도 진폭 추정 매개변수 평가

Optimal Amplitude estimation from the SEMG(surface electromyogram) signal is important because it can be used potential sources to control prosthetics and robotics. In this paper, four representative SEMG amplitude estimation parameters(ARV:average rectified value, RMS:root mean square, MTA:mean turn amplitude, MSA:mean spike amplitude) were evaluated based on probabilistic information theory, which determine the amount of information that each parameter is able to extract from SEMG signal. Surface EMG signals from eleven subjects were recorded in biceps brachii muscle with constant isometric 20, 50, and 80%MVC contractions. The parameters were investigated by the amount of mutual information between stimulus(contraction level) and response(amplitude estimation parameter) variables. Results of this study show there are no statistical significant differences(p<0.05) in the point of amount of information among the four variables. Although the evaluation method suggested here were applied to amplitude estimation parameters, it can also be considered as alternative tool to evaluate various processing technique in different areas of surface EMG analysis.

Valence opponency in peripheral olfactory processing

Significance Are olfactory receptor neurons (ORNs) arranged in a functionally meaningful manner to facilitate information processing? Here, we address this long-standing question by uncovering a valence map in the olfactory periphery of Drosophila . Within sensory hairs, we find that neighboring ORNs antagonistically regulate behaviors: stereotypically compartmentalized large- and small-spike ORNs, recognized by their characteristic spike amplitudes, either promote or inhibit the same type of behavior, respectively. Systematic optogenetic and thermogenetic assays—covering the majority of antennal sensilla—highlight a valence-opponent organization. Critically, odor-mixture behavioral experiments show that lateral inhibition between antagonistic ORNs mediates robust behavioral decisions in response to countervailing cues. Computational modeling predicts that the robustness of behavioral output depends on odor mixture ratios.

Kinase inhibitor-induced cardiotoxicity assessed in vitro with human pluripotent stem cell derived cardiomyocytes

Many small molecule kinase inhibitors (SMKIs), used predominantly in cancer therapy, have been implicated in serious clinical cardiac adverse events, which means that traditional preclinical drug development assays were not sufficient for identifying these cardiac liabilities. To improve clinical cardiac safety predictions, the effects of SMKIs targeting many different signaling pathways were studied using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) in combined assays designed for the detection of both electrophysiological (proarrhythmic) and non-electrophysiological (non-proarrhythmic) drug-induced cardiotoxicity. Several microplate-based assays were used to quantitate cell death, apoptosis, mitochondrial damage, energy depletion, and oxidative stress as mechanism-based non-electrophysiological cardiomyocyte toxicities. Microelectrode arrays (MEA) were used to quantitate in vitro arrhythmic events (iAEs), field potential duration (FPD) prolongation, and spike amplitude suppression (SAS) as electrophysiological effects. To enhance the clinical relevance, SMKI-induced cardiotoxicities were compared by converting drug concentrations into multiples of reported clinical maximum therapeutic plasma concentration, “FoldCmax”, for each assay. The results support the conclusion that the combination of the hPSC-CM based electrophysiological and non-electrophysiological assays have significantly more predictive value than either assay alone and significantly more than the current FDA-recommended hERG assay. In addition, the combination of these assays provided mechanistic information relevant to cardiomyocyte toxicities, thus providing valuable information on potential drug-induced cardiotoxicities early in drug development prior to animal and clinical testing. We believe that this early information will be helpful to guide the development of safer and more cost-effective drugs.

Fault Injection Attacks in Spiking Neural Networks and Countermeasures

Spiking Neural Networks (SNN) are fast emerging as an alternative option to Deep Neural Networks (DNN). They are computationally more powerful and provide higher energy-efficiency than DNNs. While exciting at first glance, SNNs contain security-sensitive assets (e.g., neuron threshold voltage) and vulnerabilities (e.g., sensitivity of classification accuracy to neuron threshold voltage change) that can be exploited by the adversaries. We explore global fault injection attacks using external power supply and laser-induced local power glitches on SNN designed using common analog neurons to corrupt critical training parameters such as spike amplitude and neuron’s membrane threshold potential. We also analyze the impact of power-based attacks on the SNN for digit classification task and observe a worst-case classification accuracy degradation of −85.65%. We explore the impact of various design parameters of SNN (e.g., learning rate, spike trace decay constant, and number of neurons) and identify design choices for robust implementation of SNN. We recover classification accuracy degradation by 30–47% for a subset of power-based attacks by modifying SNN training parameters such as learning rate, trace decay constant, and neurons per layer. We also propose hardware-level defenses, e.g., a robust current driver design that is immune to power-oriented attacks, improved circuit sizing of neuron components to reduce/recover the adversarial accuracy degradation at the cost of negligible area, and 25% power overhead. We also propose a dummy neuron-based detection of voltage fault injection at ∼1% power and area overhead each.

Lattice Boltzmann simulation of three-dimensional fluid interfacial instability coupled with surface tension

In this paper, the development of three-dimensional fluid interfacial Rayleigh-Taylor (RT) instability coupled with the surface tension was numerically studied using the mesoscopic lattice Boltzmann method. We mainly analyzed the influence of surface tension on fluid interfacial dynamics and spike/bubble late-time growth. The numerical experiments show that there exists the critical surface tension (&lt;inline-formula&gt;&lt;tex-math id="M3"&gt;\begin{document}$\sigma_{\rm{c}}$\end{document}&lt;/tex-math&gt;&lt;alternatives&gt;&lt;graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="4-20212061_M3.jpg"/&gt;&lt;graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="4-20212061_M3.png"/&gt;&lt;/alternatives&gt;&lt;/inline-formula&gt;) in the three-dimensional RT instability, above which the RT phenomenon does not appear and below which it would take place. It is found that the critical surface tension increases with the fluid Atwood number and the corresponding numerical predictions show good agreements with those of the theoretical analysis &lt;inline-formula&gt;&lt;tex-math id="M4"&gt;\begin{document}${\sigma_{\rm{c}}}= {{({{\rho_{\rm{h}}}-{\rho_{\rm{l}}}})g}}/{{{k^2}}}$\end{document}&lt;/tex-math&gt;&lt;alternatives&gt;&lt;graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="4-20212061_M4.jpg"/&gt;&lt;graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="4-20212061_M4.png"/&gt;&lt;/alternatives&gt;&lt;/inline-formula&gt;. In addition, we can find that increasing surface tension reduces the roll-up of the interface and the complexity of interfacial structure, also preventing the breakup of the interface into the individual droplets. The late-time dynamics of phase interface change from the asymmetric development to the symmetry with respect to the middle axis. When the surface tension is sufficiently low, the spike and bubble amplitudes almost no longer change with it, and further increasing the surface tension can slow down the growth of the spike and bubble amplitudes. Furthermore, we can observe that the development of the high-Reynolds-number RT instability under different surface tensions can also be divided into four distinct stages, including the linear growth, saturated velocity growth, reacceleration, and chaotic mixing. The spike and bubble grow with approximately constant velocities at the saturated stage and their asymptotic values are consistent with those of the modified potential flow theory. In the following, the spike and bubble driven by the increasing Kelvin-Helmholtz vortices are accelerated such that their evolutional velocities exceed the solutions of the potential flow model at the reacceleration stage. The reacceleration stage cannot last infinitely and the spike and bubble velocities at the late time fluctuate with time, implying that the growth of the RT instability enters into the chaotic mixing stage. By numerical analysis, we demonstrate that the three-dimensional RT instability at the chaotic mixing stage has a quadratic growth and also report that the spike and bubble growth rates decrease with the surface tension in general.

Is escitalopram safe to use as an antidepressant in epilepsy patients?

Objective: Epilepsy is a devastating neurological disorder with several cognitive or psychiatric comorbidities, including anxiety, autism spectrum disorder, and depressive disorder. It is known that long-term drug treatment in epileptic patients increases the incidence of depression. Thus, patients with epilepsy who later developed depressive symptoms usually require to use of antidepressant medication throughout their epilepsy treatment. However, selective serotonin reuptake inhibitors (SSRIs) derived from antidepressant drugs could have bidirectional effects on seizure activity. This experimental study was designed to determine the impact on the epileptiform activity of escitalopram in a penicillin-induced seizure model. Method: Administration of penicillin (500 IU, 2.5 μL, intracortical) into the somatomotor cortex of Wistar albino male rats triggered epileptiform activity. Electrocorticography of seizure activity was recorded for 180 min. Escitalopram, at doses of 5, 10, and 20 mg/kg, was administered 30 min after the penicillin injection. Results: While escitalopram, at doses of 5 and 10 mg/kg, increased the mean spike frequency for 180 min compared with the penicillin group, the 20 mg/kg dose caused a marked increase in the mean spike frequency and amplitude of seizure activity. Conclusion: The electrophysiological data propose that escitalopram, used for treating depression, has proconvulsant effects in penicillin-induced seizure activity. Therefore, other SSRIs, especially escitalopram, must be used with great care. The mechanism of action needs to be clarified in further detailed studies.

Electrophysiological confrontation of Lead-DBS-based electrode localizations in patients with Parkinson’s disease undergoing deep brain stimulation

Microelectrode recordings (MERs) are often used during deep brain stimulation (DBS) surgeries to confirm the position of electrodes in patients with advanced Parkinson’s disease.The present study focused on 32 patients who had undergone DBS surgery for advanced Parkinson’s disease. The first objective was to confront the anatomical locations of intraoperative individual MERs as determined electrophysiologically with those determined postoperatively by image reconstructions. The second aim was to search for differences in cell characteristics among the three subthalamic nucleus (STN) subdivisions and between the STN and other identified subcortical structures.Using the DISTAL atlas implemented in the Lead-DBS image reconstruction toolbox, each MER location was determined postoperatively and attributed to specific anatomical structures (sensorimotor, associative or limbic STN; substantia nigra [SN], thalamus, nucleus reticularis polaris, zona incerta [ZI]). The STN dorsal borders determined intraoperatively from electrophysiology were then compared with the STN dorsal borders determined by the reconstructed images. Parameters of spike clusters (firing rates, amplitudes – with minimum amplitude of 60 μV -, spike durations, amplitude spectral density of β-oscillations) were compared between structures (ANOVAs on ranks).Two hundred and thirty one MERs were analyzed (144 in 34 STNs, 7 in 4 thalami, 5 in 4 ZIs, 34 in 10 SNs, 41 others). The average difference in depth of the electrophysiological dorsal STN entry in comparison with the STN entry obtained with Lead-DBS was found to be of 0.1 mm (standard deviation: 0.8 mm). All 12 analyzed MERs recorded above the electrophysiologically-determined STN entry were confirmed to be in the thalamus or zona incerta. All MERs electrophysiologically attributed to the SN were confirmed to belong to this nucleus. However, 6/34 MERs that were electrophysiologically attributed to the ventral STN were postoperatively reattributed to the SN. Furthermore, 44 MERs of 3 trajectories, which were intraoperatively attributed to the STN, were postoperatively reattributed to the pallidum or thalamus.MER parameters seemed to differ across the STN, with higher spike amplitudes (H = 10.64, p < 0.01) and less prevalent β-oscillations (H = 9.81, p < 0.01) in the limbic STN than in the sensorimotor and associative subdivisions. Some cells, especially in the SN, showed longer spikes with lower firing rates, in agreement with described characteristics of dopamine cells. However, these probabilistic electrophysiological signatures might become clinically less relevant with the development of image reconstruction tools, which deserve to be applied intraoperatively.

Impact of High-Dose Irradiation on Human iPSC-Derived Cardiomyocytes Using Multi-Electrode Arrays: Implications for the Antiarrhythmic Effects of Cardiac Radioablation.

Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3–6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6–12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25–30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.

Design Of Digital Code Using Trellis Code to Improve Multiple Moving Target Detection in Doppler Radar

Objective: Model the digital codes to enhance the detection of desired target in Multi-object environment. Methods: This study presents an effective mathematical model using convolution code, Trellis Code, and Quadratic Residue Technique to increases the probability of moving target detection. Findings: The proposed digital codes are efficient in detecting and tracking battle-field targets, slow-moving targets (helicopters, fighter aircraft), and fast moving ICBM (Inter-Continental Ballistic Missile). Application: The proposed approach can be used in surveillance, defense, and monitoring the weather forecast. It also provides an opportunity for researchers to improve the methodology for fast-moving targets at desired Doppler frequency. Novelty: This approach improves the merit factor (MF) of the main lobe and also reduces the amplitude of the side spikes below the threshold limit by creating multiple clear windows at various Doppler ranges. To authenticate the proposed model, a comparison between the proposed model and the existing model is presented. The work has been validated using Mat- Lab. Keywords: Quad code; trellis coding Technique; Doppler; Mat lab; Side spikes

The Potential Role of Previous Physical Exercise Program to Reduce Seizure Susceptibility: A Systematic Review and Meta-Analysis of Animal Studies

Background: Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical exercise programs. In contrast to the influence of exercise after epilepsy previously established, various studies have been conducted attempting to investigate whether physical activity reduces brain susceptibility to seizures or prevents epilepsy. We report a systematic review and meta-analysis of different animal models that addressed the impact of previous physical exercise programs to reduce seizure susceptibility.Methods: We included animal model (rats and mice) studies before brain insult that reported physical exercise programs compared with other interventions (sham, control, or naïve). We excluded studies that investigated animal models after brain insult, associated with supplement nutrition or drugs, that did not address epilepsy or seizure susceptibility, ex vivo studies, in vitro studies, studies in humans, or in silico studies. Electronic searches were performed in the MEDLINE (PubMed), Web of Science (WOS), Scopus, PsycINFO, Scientific Electronic Library Online (SciELO) databases, and gray literature, without restrictions to the year or language of publication. We used SYRCLE's risk of bias tool and CAMARADES checklist for study quality. We performed a synthesis of results for different types of exercise and susceptibility to seizures by random-effects meta-analysis.Results: Fifteen studies were included in the final analysis (543 animals), 13 of them used male animals, and Wistar rats were the most commonly studied species used in the studies (355 animals). The chemoconvulsants used in the selected studies were pentylenetetrazol, penicillin, kainic acid, pilocarpine, and homocysteine. We assessed the impact of study design characteristics and the reporting of mitigations to reduce the risk of bias. We calculated a standardized mean difference effect size for each comparison and performed a random-effects meta-analysis. The meta-analysis included behavioral analysis (latency to seizure onset, n = 6 and intensity of motor signals, n = 3) and electrophysiological analysis (spikes/min, n = 4, and amplitude, n = 6). The overall effect size observed in physical exercise compared to controls for latency to seizure onset was −130.98 [95% CI: −203.47, −58.49] (seconds) and the intensity of motor signals was −0.40 [95% CI: −1.19, 0.40] (on a scale from 0 to 5). The largest effects were observed in electrophysiological analysis for spikes/min with −26.96 [95% CI: −39.56, −14.36], and for spike amplitude (μV) with −282.64 [95% CI: −466.81, −98.47].Discussion: Limitations of evidence. A higher number of animal models should be employed for analyzing the influence of exerciseon seizure susceptibility. The high heterogeneity in our meta-analysis is attributable to various factors, including the number of animals used in each study and the limited number of similar studies. Interpretation. Studies selected in this systematic review and meta-analysis suggest that previous physical exercise programs can reduce some of the main features related to seizure susceptibility [latency seizure onset, spikes/min, and spike amplitude (μV)] induced by the administration of different chemoconvulsants.Systematic Review Registration: PROSPERO, identifier CRD42021251949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251949.

In vivo blue light illumination for optogenetic inhibition: effect on local temperature and excitability of the rat hippocampus

Objective. The blue light-activated inhibitory opsin, stGtACR2, is gaining prominence as a neuromodulatory tool due its ability to shunt-inhibit neurons and is being frequently used in in vivo experimentation. However, experiments involving stGtACR2 use longer durations of blue light pulses, which inadvertently heat up the local brain tissue and confound experimental results. Therefore, the heating effects of illumination parameters used for in vivo optogenetic inhibition must be evaluated. Approach. To assess blue light (473 nm)-induced heating of the brain, we used a computational model as well as direct temperature measurements using a fiber Bragg grating (FBG). The effects of different light power densities (LPDs) and pulse durations on evoked potentials (EP) recorded from dentate gyrus were assessed. For opsin-negative rats, LPDs between 127 and 636 mW mm−2 and pulse durations between 20 and 5120 ms were tested while for stGtACR2 expressing rats, LPD of 127 mW mm−2 and pulse durations between 20 and 640 ms were tested. Main results. Increasing LPDs and pulse durations logarithmically increased the peak temperature and significantly decreased the population spike (PS) amplitude and latencies of EPs. For a pulse duration of 5120 ms, the tissue temperature increased by 0.6 °C–3.4 °C. All tested LPDs decreased the PS amplitude in opsin-negative rats, but 127 mW mm−2 had comparatively minimal effects and a significant effect of increasing light pulse duration was seen from 320 ms and beyond. This corresponded with an average temperature increase of 0.2 °C–1.1 °C at the recorded site. Compared to opsin-negative rats, illumination in stGtACR2-expressing rats resulted in much greater inhibition of EPs. Significance. Our study demonstrates that light-induced heating of the brain can be accurately measured in vivo using FBG sensors. Such light-induced heating alone can affect neuronal excitability. Useful neuromodulation by the activation of stGtACR2 is still possible while minimizing thermal effects.

Electrophysiological study of the interactive role of the cannabinoid breakdown inhibitors and L-type calcium channels on granular neurons in the hippocampal dentate gyrus in rats

ABSTRACT The interaction between L-type voltage-dependent Ca2+ channels and the endocannabinoid system (eCs) in synaptic plasticity is controversial. In the present research, the impact of acute administration of URB597, as an endocannabinoid breakdown inhibitor, was evaluated after chronic injection of verapamil, as a Ca2+ channels blocker, on inducing long-term potentiation (LTP) in the rat’s hippocampal dentate gyrus (DG). Treatment of male Wistar rats was done using intraperitoneal(i.p) injection of verapamil hydrochloride (n = 8) and saline (n = 10), as the solvent of verapamil once a day within 13 days. Anesthetization was done by i.p injection of urethane and the rats were located in the stereotaxic apparatus for surgery, electrode implantation, and field potential recording. After observing a steady-state baseline response, saline or URB597 were injected (n = 9). Measurement of the population spike (PS) amplitude and slope of field excitatory postsynaptic potentials (fEPSPs) in the DG region was performed as a result of perforant pathway (PP) stimulation. Our treatments could inhibit LTP. Our results indicated that the chronic administration of verapamil produced a significant decrease in the slope of fEPSP and PS amplitude. Also, acute URB597 administration decreased the slope of fEPSP and PS amplitude compared to the saline group. Moreover, URB597 administration in combination with chronic administration of verapamil produced a greater decrease in fEPSP slope and PS amplitude than the saline group. These findings indicated that verapamil and URB597 disrupted LTP induction in the DG. Moreover, an interaction was observed between Ca2+ channels and eCs. Therefore, the eCs possibly play a selective role in synaptic plasticity.

Multiphase rheology as a cause for stick-slip like melt extraction

When partial melting is parametrized in numerical thermo-mechanical models in a straightforward manner, it directly relates to variations in temperature. However, melt extraction is, to our knowledge rarely taken into account in these models, even if melt extraction and escape have a key influence on the mechanical behaviour of the entire system. Here, we propose a first step towards a numerical simulation for melt extraction in partially molten portions of the continental crust. We use a Lagrangian description, considering a discrete mineral distribution at sample scale. A cellular automaton mimics the mobile melt phase moving from cell to cell. An infinite source and sink for the melt and lateral periodic boundaries avoid melt accumulation. Time is represented by a proxy through successive iterations. The major controlling factors are the initial bulk melt percentage and a threshold controlling melt escape. We test pure and simple shear conditions to simulate strain partitioning between the melt and its matrix. The parameters, provided they do not vary, determine a regular or steady state amount of melt extraction after a few iterations. In contrast, for varying parameters during a single run, the quantity of melt extracted at each step presents alternate variations in amplitude (σμ) around an average value. Variations are neither periodic in the sense of a sinusoidal wave, nor of equal amplitude. Melt extraction behaves similar to a stick-slip motion in dry friction. Since we cannot have access to the prediction of melt amount, w test the origin of the sporadic motion. We examine variations of the input parameters (initial melt ϕ, permeability ζ, applied stress σ or τ). The transient effects mark by spikes (Δμ) with two contrasted situations. Return to a steady state is exponential, similar to the discharge of a capacitor. Nevertheless, a first mode occurs when the changes are made on separate runs, reinitializing the parameters between them. These experiments show a linear dependence of the variation in amplitude of σμ with the parameters. Alternatively, when the changes are successive during the same run, then σμ decreases accordingly. The exponential variation is interpreted as a memory effect or hysteretic behaviour of melt extraction. Similarly, the amplitude of the stiction spikes (Δμ) does not show the same behaviour when permeability increases or decreases. By analogy with friction, the change from sticking to slipping is interpreted as a manifestation of pinning and depinning, leading to an avalanche-like phenomena. Mechanically they correspond to a change in friction velocity. Physically, it points to the change in the free energy of the system, with a first derivative akin to velocity and a second derivative akin to acceleration. During melting, the mechanical barriers correspond to the energy variations due to chemical reactions between melt and crystals. Depinning corresponds to enhanced melting whereas pinning links with back reactions leading to garnet growth. The sporadic melt extraction links dry friction to poroelastic flow, or more generally to a consequence of two-phases rheology. Hence the sporadic motion of the weak phase originates from interactions with its matrix. Hence the flow (velocity) suffers modulations due to interactions with chemical potential (back-reaction, melting), entropy (ordering through dislocation creep), and strain (aperture of porous flow). Such interactions should be considered when dealing with quantitative mush (melt+ matrix) modeling (rejuvenation, extrusion).

Comparison of the subsequent LTP in hippocampal synapses primed by low frequency stimulations ranging from 0.5 to 5 Hz: An in vivo study

According to the Bienenstock,Cooper, andMunro’s (BCM) model, the level of afferent activity regulates the point of crossover from long-term depression (LTD) to long-term potentiation (LTP) of the active synapses. Although experimental results from the hippocampus and visual cortex have supported the BCM theory, it remains unclear whether previous activity of synapses regulates the output of neuron populations in vivo, as expected from the theory. In the present study, we studied the effects of priming stimulations at different frequencies (LFS, 0.5, 1, 2 and 5 Hz) on the magnitude of LTP at synaptic and somatic levels in the dentate gyrus of hippocampal formation. LTP in the dentate gyrus (DG) of LFS-primed or unprimed hippocampal formation was induced by delivering of tetanic stimulation to the perforant pathway (PP) in anesthetized rats. The field excitatory postsynaptic potential (fEPSP) slope and the population spike (PS) amplitude were evaluated to measure the magnitude of LTP. 1 Hz- and 5 Hz- (not 0.5 Hz and 2 Hz) stimulation of the PP led to an early LTD of fEPSP. The LTP of fEPSP was completely inhibited by previously delivering 0.5 Hz and 2 Hz LFS, but instead converted to LTD by 1 Hz LFS. However, none of the frequencies used was able to inhibit the LTP of PS. These results suggest that temporal dynamics which are critical to determine the direction of synaptic plasticity has no impact on the plasticity of neuronal output. We concluded that it is needed to explain why neuronal output does not behave within the framework of the BCM theory.