Plateau Potentials Research Articles

Deficits in integrative NMDA receptors caused by Grin1 disruption can be rescued in adulthood

Glutamatergic NMDA receptors (NMDAR) are critical for cognitive function, and their reduced expression leads to intellectual disability. Since subpopulations of NMDARs exist in distinct subcellular environments, their functioning may be unevenly vulnerable to genetic disruption. Here, we investigate synaptic and extrasynaptic NMDARs on the major output neurons of the prefrontal cortex in mice deficient for the obligate NMDAR subunit encoded by Grin1 and wild-type littermates. With whole-cell recording in brain slices, we find that single, low-intensity stimuli elicit surprisingly-similar glutamatergic synaptic currents in both genotypes. By contrast, clear genotype differences emerge with manipulations that recruit extrasynaptic NMDARs, including stronger, repetitive, or pharmacological stimulation. These results reveal a disproportionate functional deficit of extrasynaptic NMDARs compared to their synaptic counterparts. To probe the repercussions of this deficit, we examine an NMDAR-dependent phenomenon considered a building block of cognitive integration, basal dendrite plateau potentials. Since we find this phenomenon is readily evoked in wild-type but not in Grin1-deficient mice, we ask whether plateau potentials can be restored by an adult intervention to increase Grin1 expression. This genetic manipulation, previously shown to restore cognitive performance in adulthood, successfully rescues electrically-evoked basal dendrite plateau potentials after a lifetime of NMDAR compromise. Taken together, our work demonstrates NMDAR subpopulations are not uniformly vulnerable to the genetic disruption of their obligate subunit. Furthermore, the window for functional rescue of the more-sensitive integrative NMDARs remains open into adulthood.

Sodium-mediated plateau potentials in an identified decisional neuron contribute to feeding-related motor pattern genesis in Aplysia.

Motivated behaviors such as feeding depend on the functional properties of decision neurons to provide the flexibility required for behavioral adaptation. Here, we analyzed the ionic basis of the endogenous membrane properties of an identified decision neuron (B63) that drive radula biting cycles underlying food-seeking behavior in Aplysia. Each spontaneous bite cycle arises from the irregular triggering of a plateau-like potential and resultant bursting by rhythmic subthreshold oscillations in B63's membrane potential. In isolated buccal ganglion preparations, and after synaptic isolation, the expression of B63's plateau potentials persisted after removal of extracellular calcium, but was completely suppressed in a tetrodotoxin (TTX)- containing bath solution, thereby indicating the contribution of a transmembrane Na+ influx. Potassium outward efflux through tetraethylammonium (TEA)- and calcium-sensitive channels was found to contribute to each plateau's active termination. This intrinsic plateauing capability, in contrast to B63's membrane potential oscillation, was blocked by the calcium-activated non-specific cationic current (ICAN) blocker flufenamic acid (FFA). Conversely, the SERCA blocker cyclopianozic acid (CPA), which abolished the neuron's oscillation, did not prevent the expression of experimentally evoked plateau potentials. These results therefore indicate that the dynamic properties of the decision neuron B63 rely on two distinct mechanisms involving different sub-populations of ionic conductances.

Novel Structural Design and Adsorption/Insertion Coordinating Quasi-Metallic Na Storage Mechanism toward High-performance Hard Carbon Anode Derived from Carboxymethyl Cellulose.

Hard Carbon have become the most promising anode candidates for sodium-ion batteries, but the poor rate performance and cycle life remain key issues. In this work, N-doped hard carbon with abundant defects and expanded interlayer spacing is constructed by using carboxymethyl cellulose sodium as precursor with the assistance of graphitic carbon nitride. The formation of N-doped nanosheet structure is realized by the CN• or CC• radicals generated through the conversion of nitrile intermediates in the pyrolysis process. This greatly enhances the rate capability (192.8 mAh g-1 at 5.0 A g-1 ) and ultra-long cycle stability (233.3 mAh g-1 after 2000 cycles at 0.5 A g-1 ). In situ Raman spectroscopy, ex situ X-ray diffraction and X-ray photoelectron spectroscopy analysis in combination with comprehensive electrochemical characterizations, reveal that the interlayer insertion coordinated quasi-metallic sodium storage in the low potential plateau region and adsorption storage in the high potential sloping region. The first-principles density functional theory calculations further demonstrate strong coordination effect on nitrogen defect sites to capture sodium, especially with pyrrolic N, uncovering the formation mechanism of quasi-metallic bond in the sodium storage. This work provides new insights into the sodium storage mechanism of high-performance carbonaceous materials, and offers new opportunities for better design of hard carbon anode.

Reversible Ammonium Ion Intercalation/de-intercalation with Crystal Water Promotion Effect in Layered VOPO4·2H2O.

The non-metal NH4+ carrier has attracted tremendous interests for aqueous energy storage owing to its light molar mass and fast diffusion in aqueous electrolytes. Previous study inferred that NH4+ ion storage in layered VOPO4∙2H2O is impossible due to the removal of NH4+ from NH4VOPO4 leads to a phase change inevitably. Herein, we update this cognition and demonstrated highly reversible intercalation/de-intercalation behavior of NH4+ in layered VOPO4·2H2O host. Satisfactory specific capacity of 154.6 mAh g-1 at 0.1 A g-1 and very stable discharge potential plateau at 0.4 V based on reference electrode was achieved in VOPO4·2H2O. A rocking-chair ammonium-ion full cell with the VOPO4·2H2O // 2.0 M NH4OTf // PTCDI configuration exhibited a specific capacity of 55 mAh g-1, an average operating voltage of about 1.0 V and excellent long-term cycling stability over 500 cycles with a coulombic efficiency of ~99 %. Theoretical DFT calculations suggest a unique crystal water substitution process by ammonium ion during the intercalation process. Our results provide new insight into the intercalation/de-intercalation of NH4+ ions in layered hydrated phosphates through crystal water enhancement effect.

Reversible Ammonium Ion Intercalation/de‐intercalation with Crystal Water Promotion Effect in Layered VOPO4⋅2 H2O**

AbstractThe non‐metal NH4+ carrier has attracted tremendous interests for aqueous energy storage owing to its light molar mass and fast diffusion in aqueous electrolytes. Previous study inferred that NH4+ ion storage in layered VOPO4⋅2 H2O is impossible due to the removal of NH4+ from NH4VOPO4 leads to a phase change inevitably. Herein, we update this cognition and demonstrated highly reversible intercalation/de‐intercalation behavior of NH4+ in layered VOPO4⋅2 H2O host. Satisfactory specific capacity of 154.6 mAh g−1 at 0.1 A g−1 and very stable discharge potential plateau at 0.4 V based on reference electrode was achieved in VOPO4⋅2 H2O. A rocking‐chair ammonium‐ion full cell with the VOPO4⋅2 H2O//2.0 M NH4OTf//PTCDI configuration exhibited a specific capacity of 55 mAh g−1, an average operating voltage of about 1.0 V and excellent long‐term cycling stability over 500 cycles with a coulombic efficiency of ≈99 %. Theoretical DFT calculations suggest a unique crystal water substitution process by ammonium ion during the intercalation process. Our results provide new insight into the intercalation/de‐intercalation of NH4+ ions in layered hydrated phosphates through crystal water enhancement effect.

Roll-to-roll solvent-free manufactured electrodes for fast-charging batteries

Roll-to-roll solvent-free manufactured electrodes for fast-charging batteries

Spike-driven multi-scale learning with hybrid mechanisms of spiking dendrites

Neural dendrites play a critical role in various cognitive functions, including spatial navigation, sensory processing, adaptive learning, and perception. The spatial layout, signal processing, and nonlinear dynamics of dendrites endow them with these abilities. However, designing an efficient learning mechanism with spiking dendrites remains a challenging problem. In this article, a novel biologically plausible learning method is developed to address this challenge. The method uses a multi-scale learning rule with dendritic predictive characteristics. A two-phase learning mechanism based on burst-related plateau potential dynamics of spiking dendrites is utilized to achieve global learning of the spiking model. Experimental results demonstrate that the proposed algorithm can improve the learning accuracy and reduce the synaptic operations compared to the previous dendritic learning rule without dendritic predictive mechanism. It effectively reduces both the synaptic operations and the spike number in the output layer, leading to a reduction of power consumption on neuromorphic hardware. This suggests the multi-scale combination of the three-factor dendritic prediction principle and two-phase plateau potential activities can enhance the learning capability and sparsity within a single neuron. Besides, our learning method enhances the robustness and improves the learning convergence speed. We also explore different model variation formations of our learning model. The proposed study can contribute to spike-based machine learning and neuromorphic computing. It is also meaningful for a deeper understanding of the dendritic roles on biologically plausible credit assignment in the brain cortex.

ABT-333 (Dasabuvir) Increases Action Potential Duration and Provokes Early Afterdepolarizations in Canine Left Ventricular Cells via Inhibition of IKr.

ABT-333 (dasabuvir) is an antiviral agent used in hepatitis C treatment. The molecule, similarly to some inhibitors of hERG channels, responsible for the delayed rectifier potassium current (IKr), contains the methanesulfonamide group. Reduced IKr current leads to long QT syndrome and early afterdepolarizations (EADs), therefore potentially causing life-threatening arrhythmias and sudden cardiac death. Our goal was to investigate the acute effects of ABT-333 in enzymatically isolated canine left ventricular myocardial cells. Action potentials (APs) and ion currents were recorded with a sharp microelectrode technique and whole-cell patch clamp, respectively. Application of 1 μM ABT-333 prolonged the AP in a reversible manner. The maximal rates of phases 0 and 1 were irreversibly decreased. Higher ABT-333 concentrations caused larger AP prolongation, elevation of the early plateau potential, and reduction of maximal rates of phases 0, 1, and 3. EADs occurred in some cells in 3-30 μM ABT-333 concentrations. The 10 μM ABT-333-sensitive current, recorded with AP voltage clamp, contained a late outward component corresponding to IKr and an early outward one corresponding to transient outward potassium current (Ito). ABT-333 reduced hERG-channel-mediated ion current in a concentration-dependent, partially reversible manner with a half-inhibitory concentration of 3.2 μM. As the therapeutic plasma concentration of ABT-333 can reach the low μM range, ABT-333 application carries a risk of cardiac side effects especially in case of coadministration with strong inhibitors of CYP2C8.

Partial Modification Strategies of NASICON-Type Na3V2(PO4)3 Materials for Cathodes of Sodium-Ion Batteries: Progress and Perspectives

Sodium-ion batteries (SIBs) are regarded as an important substitute for lithium-ion batteries (LIBs) due to their abundant and widespread raw material resources. The choice of the cathode has a great influence on the electrochemical performance of the battery, and Na3V2(PO4)3 (NVP) is one of the most promising cathodes for SIBs. Its special NASICON (Na superionic conductor) three-dimensional structure is conducive to achieving excellent structural and thermal stability during the charging and discharging process. Moreover, it has a flat sodiation/desodiation potential plateau and rapid sodium diffusion kinetics. However, the weak intrinsic conductivity limits its further application in the market. Fortunately, there are some strategies, like doping foreign ions, modifying the carbon coating, constructing NVP-based heterogeneous composite materials, and changing the morphology of NVP particles, that are powerful approaches to solve this problem. Herein, the structure and some modification strategies (i.e., foreign ion doping, carbon coating, and construction of NVP-based heterogeneous composite materials) of NVP are carefully reviewed. Finally, we summarized this paper and explored the future development of the NVP cathode.

Plateau potentials contribute to myotonia in mouse models of myotonia congenita.

It has long been accepted that myotonia (muscle stiffness) in patients with muscle channelopathies is due to myotonic discharges (involuntary firing of action potentials). In a previous study, we identified a novel phenomenon in myotonic muscle: development of plateau potentials, transient depolarizations to near -35mV lasting for seconds to minutes. In the current study we examined whether plateau potentials contribute to myotonia. A recessive genetic model (ClCadr mice) with complete loss of muscle chloride channel (ClC-1) function was used to model severe myotonia congenita with complete loss of ClC-1 function and a pharmacologic model using anthracene-9-carboxylic acid (9AC) was used to model milder myotonia congenita with incomplete loss of ClC-1 function. Simultaneous measurements of action potentials and myoplasmic Ca2+ from individual muscle fibers were compared to recordings of whole muscle force generation. In ClCadr muscle both myotonia and plateau potentials lasted 10s of seconds to minutes. During plateau potentials lasting 1-2min, there was a gradual transition from high to low intracellular Ca2+, suggesting a transition in individual fibers from myotonia to flaccid paralysis in severe myotonia congenita. In 9AC-treated muscles, both myotonia and plateau potentials lasted only a few seconds and Ca2+ remained elevated during the plateau potentials, suggesting plateau potentials contribute to myotonia without causing weakness. We propose, that in myotonic muscle, there is a novel state in which there is contraction in the absence of action potentials. This discovery provides a mechanism to explain reports of patients with myotonia who suffer from electrically silent muscle contraction lasting minutes.

Hierarchical Ni/N/C Single‐Site Catalyst Achieving Industrial‐Level Current Density and Ultra‐Wide Potential Plateau of High CO Faradic Efficiency for CO2 Electroreduction

AbstractThe practical applications of CO2 electroreduction to CO driven by renewable electricity should simultaneously meet the requests of industrial‐level CO partial current density (JCO) at least 100 mA cm−2, wide potential window of high CO faradic efficiency (FECO), and low cost. Herein, a new strategy is reported to construct porous hierarchical Ni/N/C single‐site catalyst with excellent catalytic activity via coating Ni‐containing ZIF‐8 on mesostructured basic magnesium carbonate template followed by pyrolysis. The abundant micropores facilitate the formation of numerous edge‐hosted Ni‐N4 sites with high intrinsic activity, and the interconnected macro/mesopores much promote CO2 delivery and CO release for the full expression of intrinsic activity. Consequently, the catalyst exhibits the industrial‐level JCO of 105–462 mA cm−2 at the potential range of −0.6∼−1.3 V with ultra‐wide high FECO plateau (>90%@−0.4∼−1.3 V), showing great promise for practical application. This study provides a general synthetic strategy to explore high‐performance hierarchical M/N/C electrocatalysts.

Dendritic plateau potentials can process spike sequences across multiple time-scales

The brain constantly processes information encoded in temporal sequences of spiking activity. This sequential activity emerges from sensory inputs as well as from the brain's own recurrent connectivity and spans multiple dynamically changing timescales. Decoding the temporal order of spiking activity across these varying timescales is a critical function of the brain, but we do not yet understand its neural implementation. The problem is, that the passive dynamics of neural membrane potentials occur on a short millisecond timescale, whereas many cognitive tasks require the integration of information across much slower behavioral timescales. However, actively generated dendritic plateau potentials do occur on such longer timescales, and their essential role for many aspects of cognition has been firmly established by recent experiments. Here, we build on these discoveries and propose a new model of neural computation that emerges from the interaction of localized plateau potentials across a functionally compartmentalized dendritic tree. We show how this interaction offers a robust solution to the timing invariant detection and processing of sequential spike patterns in single neurons. Stochastic synaptic transmission complements the deterministic all-or-none plateau process and improves information transmission by allowing ensembles of neurons to produce graded responses to continuous combinations of features. We found that networks of such neurons can solve highly complex sequence detection tasks by breaking down long inputs into sequences of shorter, random features that can be classified reliably. These results suggest that active dendritic processes are fundamental to neural computation.

Using rosetta and alphafold to assess Jingzhaotoxin-III binding to hNav1.5 and hKv2.1.

Ion channels are pore-forming transmembrane proteins regulating ion flux across cell membranes and regulators of the ventricular action potential. The human voltage-gated sodium channel 1.5 (hNav1.5) is predominantly expressed in cardiac myocytes and is solely responsible for the ventricular action potential's initial upstroke phase. A series of mutations in hNav1.5 are classified as Long QT Syndrome subtype 3 (LQT3) and are linked to hNav1.5 gain-of-function, resulting in an enhanced inward current prolonging repolarization. Alternatively, improper hNav1.5 inactivation results in a prolonged, late sodium current during the action potential plateau, causing a similar LQT3 gain-of function phenotype. Current drug therapies for hNav1.5-associated arrhythmia involve combinations of beta-adrenergic blockers and hNav1.5-targeting small-molecules such as flecainide. Alternatively, hNav1.5-targeting peptide toxins have the potential as novel therapeutics and investigational tools for ion channel disorders. One such peptide, Jingzhaotoxin-III (JzTx-III) is a 36-residue peptide that has been found to inhibit hNav1.5 and human voltage-gated potassium channel isoform 2.1 (hKv2.1) but does not inhibit neuronal and skeletal hNav channels. Mutational studies of JzTx-III identified unique residues that modulate hNav1.5 and hKv2.1 activity. We hypothesize that prior single-point mutational data will demonstrate differing sets of binding free energies and peptide-channel contacts for hNav1.5 and hKv2.1. In this study, we used AlphaFold and Rosetta to generate models of hNav1.5 and hKv2.1 in the deactivated state, docked JzTx-III to each channel, and assessed in silico binding free energies of wild-type and single-point mutations. This structural and energetic information can then be used as a guideline for multi-point mutational design to predict improved hNav1.5 binding specificity for further investigation of LQTS and pro-arrhythmic ventricular action potentials.

Supercritical Injection Modeling by an Incompressible but Variable Density Approach

Supercritical nitrogen jet behavior is modeled using an incompressible but variable density approach developed for variable density jets. Following mechanical and thermal breakup concepts, several injection conditions relevant to liquid rocket propulsion are analyzed, considering heat transfer in the injector. Regarding axial density distributions, different levels of agreement with experimental data are encountered for potential core, subsided core, and plateau formations. Further comparisons with compressible formulations from the literature are a good indicator of the proposed methodology’s suitability for the simulation of supercritical injection behavior.

The Electrochemical Behavior of Unmodified and Pd-NPs Modified AB5 Hydrogen Storage Alloy in Selected Protic and Aprotic Ionic Liquids (ILs): Towards ILs-Based Electrolytes for Ni-MH Batteries

The objective of this work was to study the electrochemical behavior of AB5 alloy and its composite with Pd nanoparticles in selected ionic liquids. The protic ionic liquid (diethylmethylammonium triflate) and the mixture of aprotic ionic liquid (1-ethyl-3-methylimidazolium methanesulfonate) with parent superacid were used as electrolytes in the process of hydrogen electrosorption in AB5 alloy electrodes. The impact of the surface modification of AB5 electrode with Pd nanoparticles has been checked. The studies revealed that the highest hydrogen absorption capacity can be obtained in Pd-NPs-AB5 electrode in DEMA-TFO. It was found that the surface modification with Pd-NPs facilitates the activation of the electrode and results in stabilization of the plateau potential of discharging. The studies show that more effort should be put into the synthesis of less corrosive tailored ionic liquids suitable to be used as electrolytes in hydride batteries.

High FeLS(C) electrochemical activity of an iron hexacyanoferrate cathode boosts superior sodium ion storage

AbstractSodium iron hexacyanoferrate (FeHCF) is one of the most promising cathode materials for sodium‐ion batteries (SIBs) due to its low cost theoretical capacity. However, the low electrochemical activity of FeLS(C) in FeHCF drags down its practical capacity and potential plateau. Herein, FeHCF with high FeLS(C) electrochemical activity (C‐FeHCF) is synthesized via a facile citric acid‐assisted solvothermal method. As the cathode of SIBs, C‐FeHCF shows superior cycling stability (ca. 87.3% capacity retention for 1000 cycles at 10 C) and outstanding rate performance (ca. 68.5% capacity retention at 50 C). Importantly, the contribution of FeLS(C) to the whole capacity was quantitatively analyzed via combining dQ/dV and discharge curve for the first time, and the index reaches 44.53% for C‐FeHCF, close to the theoretical value. In‐situ X‐ray diffraction proves the structure stability of C‐FeHCF during charge–discharge process, ensuring its superior cycling performance. Furthermore, the application feasibility of the C‐FeHCF cathode in quasi‐solid SIBs is also evaluated. The quasi‐solid SIBs with the C‐FeHCF cathode exhibit excellent electrochemical performance, delivering an initial discharge capacity of 106.5 mAh g−1 at 5 C and high capacity retention of 89.8% over 1200 cycles. This work opens new insights into the design and development of advanced cathode materials for SIBs and the beyond.

Electrochemically Generated Luminescence of Luminol and Luciferin in Ionic Liquids

AbstractElectrochemiluminescence (ECL) is the generation of light triggered by an electrochemical reaction. ECL has been extensively studied in solvent‐based electrolytes, but there is a lack of data on using electrode reactions to populate an excited‐state light emitter in room temperature ionic liquids (RTILs). This work explores the current response, light intensity (photon counting), and spectral signatures of the cathodic ECL of luminol and firefly's luciferin in imidazolium‐based RTILs. We have demonstrated that the cathodic (superoxide‐triggered) ECL of both luminol and adenylate‐ester of firefly's luciferin is viable in RTILs, explored the effect of water contaminations, and importantly, shown that the ECL signal persists for up to about 700 s after the removal of the external cathodic pulse, which is probably due to the stabilization of superoxide by double‐layer cation‐rich structures. Long‐lived RTIL double‐layer structures and their endogenous fields are detected as stable and discrete open‐circuit potential plateaus.

An Effective Field Theory for large oscillons

We consider oscillons — localized, quasiperiodic, and extremely long-living classical solutions in models with real scalar fields. We develop their effective description in the limit of large size at finite field strength. Namely, we note that nonlinear long-range field configurations can be described by an effective complex field ψ(t,x) which is related to the original fields by a canonical transformation. The action for ψ has the form of a systematic gradient expansion. At every order of the expansion, such an effective theory has a global U(1) symmetry and hence a family of stationary nontopological solitons — oscillons. The decay of the latter objects is a nonperturbative process from the viewpoint of the effective theory. Our approach gives an intuitive understanding of oscillons in full nonlinearity and explains their longevity. Importantly, it also provides reliable selection criteria for models with long-lived oscillons. This technique is more precise in the nonrelativistic limit, in the notable cases of nonlinear, extremely long-lived, and large objects, and also in lower spatial dimensions. We test the effective theory by performing explicit numerical simulations of a (d + 1)-dimensional scalar field with a plateau potential.

Consequences and Mechanisms of Left Atrium Remodeling in Aging Rabbits.

To investigate the consequences and mechanisms of myocardium remodeling of aging left atrium, we analyzed the main cardiac electrophysiological parameters such as rest membrane potential, action potential amplitude, maximum rate of action potential increase (max dV/dt), action potential plateau, and 30, 50, and 90% action potential duration (APD30, APD50, and APD90, respectively), as well as the inducibility and duration of atrial arrhythmias in adult and aging rabbits. L-type calcium current was also recorded. The collagen content in the myocardium and ultrastructure of left atrial cells were also studied. Significant changes were detected in the electrophysiological parameters and structure in aged left atrium, which can contribute to atrial susceptibility to arrhythmia in aged rabbits.

Experimental factors that impact CaV1.2 channel pharmacology-Effects of recording temperature, charge carrier, and quantification of drug effects on the step and ramp currents elicited by the "step-step-ramp" voltage protocol.

CaV1.2 channels contribute to action potential upstroke in pacemaker cells, plateau potential in working myocytes, and initiate excitation-contraction coupling. Understanding drug action on CaV1.2 channels may inform potential impact on cardiac function. However, literature shows large degrees of variability between CaV1.2 pharmacology generated by different laboratories, casting doubt regarding the utility of these data to predict or interpret clinical outcomes. This study examined experimental factors that may impact CaV1.2 pharmacology. Whole cell recordings were made on CaV1.2 overexpression cells. Current was evoked using a "step-step-ramp" waveform that elicited a step and a ramp current. Experimental factors examined were: 1) near physiological vs. room temperature for recording, 2) drug inhibition of the step vs. the ramp current, and 3) Ca2+ vs. Ba2+ as the charge carrier. Eight drugs were studied. CaV1.2 current exhibited prominent rundown, exquisite temperature sensitivity, and required a high degree of series resistance compensation to optimize voltage control. Temperature-dependent effects were examined for verapamil and methadone. Verapamil's block potency shifted by up to 4X between room to near physiological temperature. Methadone exhibited facilitatory and inhibitory effects at near physiological temperature, and only inhibitory effect at room temperature. Most drugs inhibited the ramp current more potently than the step current-a preference enhanced when Ba2+ was the charge carrier. The slopes of the concentration-inhibition relationships for many drugs were shallow, temperature-dependent, and differed between the step and the ramp current. All experimental factors examined affected CaV1.2 pharmacology. In addition, whole cell CaV1.2 current characteristics-rundown, temperature sensitivity, and impact of series resistance-are also factors that can impact pharmacology. Drug effects on CaV1.2 channels appear more complex than simple pore block mechanism. Normalizing laboratory-specific approaches is key to improve inter-laboratory data reproducibility. Releasing original electrophysiology records is essential to promote transparency and enable the independent evaluation of data quality.